Ping Yi, Jia Pang, Jonathan Steven Alexander, Chantal Rivera
Background: Postprandial lipidemia is important in the development of coronary artery disease (CAD). Consumption of a meal high in monounsaturated fat was correlated with acute impairment of endothelial function. However, the mechanisms underlying impaired endothelial function in the postprandial state have not yet been elucidated. The effects of polyunsaturated fat (corn oil) and monounsaturated fat (olive oil) on vascular dysfunction in intestinal postcapillary venules and arterioles were examined in wild-type (WT) mice, mice genetically deficient in TLR4 (TLR4-/-) and mice pre-treated with antibiotics by intravital microscopy which was performed 1.0, 1.5, 2.0, 2.5 hours after oil administration. After intravital microscopy, samples of jejunum were therefore collected to test TLR4, pNF-kB p65 and SIRT1 protein expression by western blotting.
Results: Our findings showed that feeding mono-unsaturated olive oil or polyunsaturated corn oil promoted leukocyte and platelet trafficking in the gut microvasculature, and impaired endothelium-dependent arteriolar vasodilator responses during postprandial lipidemia. The expression of TLR4, pNF-kB p65 was significantly increased in mice gavaged with olive oil at 2 h and was significantly reduced in mice gavaged for 7 days with antibiotics and in TLR4 knockout (TLR4-/-) mice. At the same time, SIRT1 protein expression is diminished by feeding olive oil for 2 h, a phenomenon that is attenuated in mice pre-treated with antibiotics and in TLR4-/- mice. Corn oil treated mice exhibited a pattern of response similar to olive oil.
Conclusions: Dietary oils may be negative regulators of SIRT1 which activate the innate immune response through the endotoxin/TLR4 axis. Our findings establish a link between innate immunity (i.e. the endotoxin/TLR4 axis) and epigenetic controls mediated by SIRT1 in the genesis of diet associated vascular stress.
背景:餐后血脂在冠状动脉疾病(CAD)的发展中起重要作用。食用单不饱和脂肪含量高的食物与内皮功能的急性损伤有关。然而,在餐后状态下内皮功能受损的机制尚未阐明。在给油后1.0、1.5、2.0、2.5小时,采用活体显微镜观察了多不饱和脂肪(玉米油)和单不饱和脂肪(橄榄油)对野生型(WT)小鼠、TLR4基因缺陷小鼠(TLR4-/-)和抗生素预处理小鼠肠道毛细血管后小静脉和小动脉血管功能障碍的影响。活体显微镜观察后,收集空肠标本,采用western blotting检测TLR4、pNF-kB、p65和SIRT1蛋白的表达。结果:我们的研究结果表明,进食单不饱和橄榄油或多不饱和玉米油可促进肠道微血管中的白细胞和血小板运输,并损害餐后血脂时内皮依赖性小动脉血管舒张剂的反应。橄榄油灌胃小鼠2 h TLR4、pNF-kB p65表达显著升高,抗生素灌胃小鼠和TLR4敲除(TLR4-/-)小鼠7 d TLR4、pNF-kB p65表达显著降低。与此同时,喂食橄榄油2小时后SIRT1蛋白表达降低,这种现象在抗生素预处理小鼠和TLR4-/-小鼠中有所减弱。玉米油处理的小鼠表现出与橄榄油相似的反应模式。结论:膳食油可能是SIRT1的负调节因子,通过内毒素/TLR4轴激活先天免疫反应。我们的研究结果建立了先天免疫(即内毒素/TLR4轴)与SIRT1介导的表观遗传控制在饮食相关血管应激发生中的联系。
{"title":"The endotoxin/toll-like receptor-4 axis mediates gut microvascular dysfunction associated with post-prandial lipidemia.","authors":"Ping Yi, Jia Pang, Jonathan Steven Alexander, Chantal Rivera","doi":"10.1186/1472-6793-13-12","DOIUrl":"https://doi.org/10.1186/1472-6793-13-12","url":null,"abstract":"<p><strong>Background: </strong>Postprandial lipidemia is important in the development of coronary artery disease (CAD). Consumption of a meal high in monounsaturated fat was correlated with acute impairment of endothelial function. However, the mechanisms underlying impaired endothelial function in the postprandial state have not yet been elucidated. The effects of polyunsaturated fat (corn oil) and monounsaturated fat (olive oil) on vascular dysfunction in intestinal postcapillary venules and arterioles were examined in wild-type (WT) mice, mice genetically deficient in TLR4 (TLR4-/-) and mice pre-treated with antibiotics by intravital microscopy which was performed 1.0, 1.5, 2.0, 2.5 hours after oil administration. After intravital microscopy, samples of jejunum were therefore collected to test TLR4, pNF-kB p65 and SIRT1 protein expression by western blotting.</p><p><strong>Results: </strong>Our findings showed that feeding mono-unsaturated olive oil or polyunsaturated corn oil promoted leukocyte and platelet trafficking in the gut microvasculature, and impaired endothelium-dependent arteriolar vasodilator responses during postprandial lipidemia. The expression of TLR4, pNF-kB p65 was significantly increased in mice gavaged with olive oil at 2 h and was significantly reduced in mice gavaged for 7 days with antibiotics and in TLR4 knockout (TLR4-/-) mice. At the same time, SIRT1 protein expression is diminished by feeding olive oil for 2 h, a phenomenon that is attenuated in mice pre-treated with antibiotics and in TLR4-/- mice. Corn oil treated mice exhibited a pattern of response similar to olive oil.</p><p><strong>Conclusions: </strong>Dietary oils may be negative regulators of SIRT1 which activate the innate immune response through the endotoxin/TLR4 axis. Our findings establish a link between innate immunity (i.e. the endotoxin/TLR4 axis) and epigenetic controls mediated by SIRT1 in the genesis of diet associated vascular stress.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31856347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruno Cesar Pereira, José Rodrigo Pauli, Lusânia Maria Greggi Antunes, Ellen Cristini de Freitas, Mara Ribeiro de Almeida, Vinícius de Paula Venâncio, Eduardo Rochete Ropelle, Claudio Teodoro de Souza, Dennys Esper Cintra, Marcelo Papoti, Adelino Sanchez Ramos da Silva
Background: The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples.
Results: Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups.
Conclusions: Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.
背景:碱性单细胞凝胶(彗星)测定法是一种量化 DNA 损伤的有用方法。虽然已经开展了一些关于慢性和急性运动对彗星测定法所测 DNA 损伤影响的研究,但目前尚不清楚明确规定强度、运动量和负荷的有氧训练方案是否能在提高运动成绩的同时不导致外周血细胞 DNA 损伤。此外,过度训练对 DNA 损伤的影响也不得而知。因此,本研究旨在研究有氧训练和过度训练对瑞士小鼠外周血和骨骼肌细胞DNA损伤的影响。为了研究这些参数可能随氧化应激而发生的变化,我们测量了总血液中还原型谷胱甘肽(GSH)的水平,以及肌肉样本中GSH水平和脂质过氧化反应:成绩评估(即增量负荷和耗竭测试)显示出显著的组内和组间差异。与对照组(C)和训练组(TR)相比,过度训练组(OTR)尾部 DNA 的百分比明显增加。OTR组的GSH水平明显低于C组和TR组。与 C 组和 TR 组相比,OTR 组的脂质过氧化水平明显更高:结论:在8周的最大乳酸稳态训练中,有氧和无氧性能参数均可得到改善,且不会导致外周血和骨骼肌细胞的DNA损伤或骨骼肌细胞的氧化应激。然而,下坡跑训练导致的过度训练与外周血和骨骼肌细胞中的DNA损伤以及骨骼肌细胞和总血液中的氧化应激有关。
{"title":"Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice.","authors":"Bruno Cesar Pereira, José Rodrigo Pauli, Lusânia Maria Greggi Antunes, Ellen Cristini de Freitas, Mara Ribeiro de Almeida, Vinícius de Paula Venâncio, Eduardo Rochete Ropelle, Claudio Teodoro de Souza, Dennys Esper Cintra, Marcelo Papoti, Adelino Sanchez Ramos da Silva","doi":"10.1186/1472-6793-13-11","DOIUrl":"10.1186/1472-6793-13-11","url":null,"abstract":"<p><strong>Background: </strong>The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples.</p><p><strong>Results: </strong>Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups.</p><p><strong>Conclusions: </strong>Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31784665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mardi S Byerly, Roy D Swanson, G William Wong, Seth Blackshaw
Background: Estrogen-related receptors (ERRs) are orphan nuclear hormone receptors expressed in metabolically active tissues and modulate numerous homeostatic processes. ERRs do not bind the ligand estrogen, but they are able to bind the estrogen response element (ERE) embedded within the ERR response elements (ERREs) to regulate transcription of genes. Previous work has demonstrated that adult mice lacking Errβ have altered metabolism and meal patterns. To further understand the biological role of Errβ, we characterized the stress response of mice deficient for one or both alleles of Errβ.
Results: Sox2-Cre:Errβ mice lack Errβ expression in all tissues of the developing embryo. Sox2-Cre:Errβ+/lox heterozygotes were obese, had increased Npy and Agrp gene expression in the arcuate nucleus of the hypothalamus, and secreted more corticosterone in response to stress. In contrast, Sox2-Cre:Errβlox/lox homozygotes were lean and, despite increased Npy and Agrp gene expression, did not secrete more corticosterone in response to stress. Sox2-Cre:Errβ+/lox and Sox2-Cre:Errβlox/lox mice treated with the Errβ and Errγ agonist DY131 demonstrated increased corticotropin-releasing hormone (Crh) expression in the paraventricular nucleus of the hypothalamus, although corticosterone levels were not affected. Nes-Cre:Errβlox/lox mice, which selectively lack Errβ expression in the nervous system, also demonstrated elevated stress response during an acoustic startle response test and decreased expression of both Crh and corticotropin-releasing hormone receptor 2 (Crhr2).
Conclusions: Loss of Errβ affects body composition, neuropeptide levels, stress hormones, and centrally-modulated startle responses of mice. These results indicate that Errβ alters the function of the hypothalamic-pituitary-adrenocortical axis and indicates a role for Errβ in regulating stress response.
{"title":"Estrogen-related receptor β deficiency alters body composition and response to restraint stress.","authors":"Mardi S Byerly, Roy D Swanson, G William Wong, Seth Blackshaw","doi":"10.1186/1472-6793-13-10","DOIUrl":"https://doi.org/10.1186/1472-6793-13-10","url":null,"abstract":"<p><strong>Background: </strong>Estrogen-related receptors (ERRs) are orphan nuclear hormone receptors expressed in metabolically active tissues and modulate numerous homeostatic processes. ERRs do not bind the ligand estrogen, but they are able to bind the estrogen response element (ERE) embedded within the ERR response elements (ERREs) to regulate transcription of genes. Previous work has demonstrated that adult mice lacking Errβ have altered metabolism and meal patterns. To further understand the biological role of Errβ, we characterized the stress response of mice deficient for one or both alleles of Errβ.</p><p><strong>Results: </strong>Sox2-Cre:Errβ mice lack Errβ expression in all tissues of the developing embryo. Sox2-Cre:Errβ+/lox heterozygotes were obese, had increased Npy and Agrp gene expression in the arcuate nucleus of the hypothalamus, and secreted more corticosterone in response to stress. In contrast, Sox2-Cre:Errβlox/lox homozygotes were lean and, despite increased Npy and Agrp gene expression, did not secrete more corticosterone in response to stress. Sox2-Cre:Errβ+/lox and Sox2-Cre:Errβlox/lox mice treated with the Errβ and Errγ agonist DY131 demonstrated increased corticotropin-releasing hormone (Crh) expression in the paraventricular nucleus of the hypothalamus, although corticosterone levels were not affected. Nes-Cre:Errβlox/lox mice, which selectively lack Errβ expression in the nervous system, also demonstrated elevated stress response during an acoustic startle response test and decreased expression of both Crh and corticotropin-releasing hormone receptor 2 (Crhr2).</p><p><strong>Conclusions: </strong>Loss of Errβ affects body composition, neuropeptide levels, stress hormones, and centrally-modulated startle responses of mice. These results indicate that Errβ alters the function of the hypothalamic-pituitary-adrenocortical axis and indicates a role for Errβ in regulating stress response.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31747687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander G Tonevitsky, Diana V Maltseva, Asghar Abbasi, Timur R Samatov, Dmitry A Sakharov, Maxim U Shkurnikov, Alexey E Lebedev, Vladimir V Galatenko, Anatoly I Grigoriev, Hinnak Northoff
Background: MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period.
Results: Here we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation.
Conclusions: We have identified metabolic pathways involved in response to exercise and revealed four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into the recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation.
{"title":"Dynamically regulated miRNA-mRNA networks revealed by exercise.","authors":"Alexander G Tonevitsky, Diana V Maltseva, Asghar Abbasi, Timur R Samatov, Dmitry A Sakharov, Maxim U Shkurnikov, Alexey E Lebedev, Vladimir V Galatenko, Anatoly I Grigoriev, Hinnak Northoff","doi":"10.1186/1472-6793-13-9","DOIUrl":"https://doi.org/10.1186/1472-6793-13-9","url":null,"abstract":"<p><strong>Background: </strong>MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period.</p><p><strong>Results: </strong>Here we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation.</p><p><strong>Conclusions: </strong>We have identified metabolic pathways involved in response to exercise and revealed four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into the recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31854724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anh Thuc Ngo, Mads Riemann, Niels-Henrik Holstein-Rathlou, Christian Torp-Pedersen, Lars Jørn Jensen
Background: ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO₂.
Results: Change from "high" oxygen tension (PO₂ = 153.4 ± 3.4 mmHg) to "low" oxygen tension (PO₂ = 13.8 ± 1.3 mmHg) dilated cremaster muscle arterioles from 11.0 ± 0.4 μm to 32.9 ± 0.9 μm (n = 28, P < 0.05). Glibenclamide (KATP channel blocker) caused maximal vasoconstriction, and abolished the dilation to low oxygen, whereas the KATP channel opener cromakalim caused maximal dilation and prevented the constriction to high oxygen. When adding cromakalim on top of glibenclamide or vice versa, the reactivity to oxygen was gradually restored. Inhibition of L-type Ca²⁺ channels using 3 μM nifedipine did not fully block basal tone in the arterioles, but rendered them unresponsive to changes in PO₂. Inhibition of the CYP450-4A enzyme using DDMS blocked vasoconstriction to an increase in PO₂, but had no effect on dilation to low PO₂.
Conclusions: We conclude that: 1) L-type Ca²⁺ channels are central to oxygen sensing, 2) KATP channels are permissive for the arteriolar response to oxygen, but are not directly involved in the oxygen sensing mechanism and 3) CYP450-4A mediated 20-HETE production is involved in vasoconstriction to high PO₂.
{"title":"Significance of K(ATP) channels, L-type Ca²⁺ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles in vivo.","authors":"Anh Thuc Ngo, Mads Riemann, Niels-Henrik Holstein-Rathlou, Christian Torp-Pedersen, Lars Jørn Jensen","doi":"10.1186/1472-6793-13-8","DOIUrl":"https://doi.org/10.1186/1472-6793-13-8","url":null,"abstract":"<p><strong>Background: </strong>ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO₂.</p><p><strong>Results: </strong>Change from \"high\" oxygen tension (PO₂ = 153.4 ± 3.4 mmHg) to \"low\" oxygen tension (PO₂ = 13.8 ± 1.3 mmHg) dilated cremaster muscle arterioles from 11.0 ± 0.4 μm to 32.9 ± 0.9 μm (n = 28, P < 0.05). Glibenclamide (KATP channel blocker) caused maximal vasoconstriction, and abolished the dilation to low oxygen, whereas the KATP channel opener cromakalim caused maximal dilation and prevented the constriction to high oxygen. When adding cromakalim on top of glibenclamide or vice versa, the reactivity to oxygen was gradually restored. Inhibition of L-type Ca²⁺ channels using 3 μM nifedipine did not fully block basal tone in the arterioles, but rendered them unresponsive to changes in PO₂. Inhibition of the CYP450-4A enzyme using DDMS blocked vasoconstriction to an increase in PO₂, but had no effect on dilation to low PO₂.</p><p><strong>Conclusions: </strong>We conclude that: 1) L-type Ca²⁺ channels are central to oxygen sensing, 2) KATP channels are permissive for the arteriolar response to oxygen, but are not directly involved in the oxygen sensing mechanism and 3) CYP450-4A mediated 20-HETE production is involved in vasoconstriction to high PO₂.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31421830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Britt-Marie Iresjö, Johan Svensson, Claes Ohlsson, Kent Lundholm
Background: Insulin-like growth factor-1 (IGF-1) is produced in various tissues to stimulate protein synthesis under different conditions. It is however, difficult to distinguish effects by locally produced IGF-1 compared to liver-derived IGF-1 appearing in the circulation. In the present study the role of liver-derived endocrine IGF-I for activation of skeletal muscle protein synthesis following feeding was evaluated.
Results: Transgenic female mice with selective knockout of the IGF-I gene in hepatocytes were freely fed, starved overnight and subsequently refed for 3 hours and compared to wild types (wt). Liver IGF-I knockout mice had 70% reduced plasma IGF-I. Starvation decreased and refeeding increased muscle protein synthesis (p < 0.01), similarly in both IGF-I knockouts and wt mice. Phosphorylation of p70s6k and mTOR increased and 4EBP1 bound to eIF4E decreased in both IGF-I knockouts and wt mice after refeeding (p < 0.05). Muscle transcripts of IGF-I decreased and IGF-I receptor increased (p < 0.01) in wild types during starvation but similar alterations did not reach significance in knockouts (p>0.05). mTOR mRNA increased in knockouts only during starvation. Plasma glucose decreased during starvation in all groups in parallel to insulin, while plasma IGF-I and GH did not change significantly among the groups during starvation-refeeding. Plasma amino acids declined and increased during starvation-refeeding in wild type mice (p < 0.05), but less so in IGF-I (-/-) knockouts (p < 0.08).
Conclusion: This study demonstrates that re-synthesis of muscle proteins following starvation is not critically dependent on endocrine liver-derived IGF-I.
{"title":"Liver-derived endocrine IGF-I is not critical for activation of skeletal muscle protein synthesis following oral feeding.","authors":"Britt-Marie Iresjö, Johan Svensson, Claes Ohlsson, Kent Lundholm","doi":"10.1186/1472-6793-13-7","DOIUrl":"https://doi.org/10.1186/1472-6793-13-7","url":null,"abstract":"<p><strong>Background: </strong>Insulin-like growth factor-1 (IGF-1) is produced in various tissues to stimulate protein synthesis under different conditions. It is however, difficult to distinguish effects by locally produced IGF-1 compared to liver-derived IGF-1 appearing in the circulation. In the present study the role of liver-derived endocrine IGF-I for activation of skeletal muscle protein synthesis following feeding was evaluated.</p><p><strong>Results: </strong>Transgenic female mice with selective knockout of the IGF-I gene in hepatocytes were freely fed, starved overnight and subsequently refed for 3 hours and compared to wild types (wt). Liver IGF-I knockout mice had 70% reduced plasma IGF-I. Starvation decreased and refeeding increased muscle protein synthesis (p < 0.01), similarly in both IGF-I knockouts and wt mice. Phosphorylation of p70s6k and mTOR increased and 4EBP1 bound to eIF4E decreased in both IGF-I knockouts and wt mice after refeeding (p < 0.05). Muscle transcripts of IGF-I decreased and IGF-I receptor increased (p < 0.01) in wild types during starvation but similar alterations did not reach significance in knockouts (p>0.05). mTOR mRNA increased in knockouts only during starvation. Plasma glucose decreased during starvation in all groups in parallel to insulin, while plasma IGF-I and GH did not change significantly among the groups during starvation-refeeding. Plasma amino acids declined and increased during starvation-refeeding in wild type mice (p < 0.05), but less so in IGF-I (-/-) knockouts (p < 0.08).</p><p><strong>Conclusion: </strong>This study demonstrates that re-synthesis of muscle proteins following starvation is not critically dependent on endocrine liver-derived IGF-I.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31508343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Satyanarayana R Pondugula, Suresh B Kampalli, Tao Wu, Robert C De Lisle, Nithya N Raveendran, Donald G Harbidge, Daniel C Marcus
Background: The vestibular system controls the ion composition of its luminal fluid through several epithelial cell transport mechanisms under hormonal regulation. The semicircular canal duct (SCCD) epithelium has been shown to secrete Cl- under β2-adrenergic stimulation. In the current study, we sought to determine the ion transporters involved in Cl- secretion and whether secretion is regulated by PKA and glucocorticoids.
Results: Short circuit current (Isc) from rat SCCD epithelia demonstrated stimulation by forskolin (EC50: 0.8 μM), 8-Br-cAMP (EC50: 180 μM), 8-pCPT-cAMP (100 μM), IBMX (250 μM), and RO-20-1724 (100 μM). The PKA activator N6-BNZ-cAMP (0.1, 0.3 & 1 mM) also stimulated Isc. Partial inhibition of stimulated Isc individually by bumetanide (10 & 50 μM), and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 μM) were additive and complete. Stimulated Isc was also partially inhibited by CFTRinh-172 (5 & 30 μM), flufenamic acid (5 μM) and diphenylamine-2,2'-dicarboxylic acid (DPC; 1 mM). Native canals of CFTR+/- mice showed a stimulation of Isc from isoproterenol and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while canals from CFTR-/- mice had no responses. Nonetheless, CFTR-/- mice showed no difference from CFTR+/- mice in their ability to balance (rota-rod). Stimulated Isc was greater after chronic incubation (24 hr) with the glucocorticoids dexamethasone (0.1 & 0.3 μM), prednisolone (0.3, 1 & 3 μM), hydrocortisone (0.01, 0.1 & 1 μM), and corticosterone (0.1 & 1 μM) and mineralocorticoid aldosterone (1 μM). Steroid action was blocked by mifepristone but not by spironolactone, indicating all the steroids activated the glucocorticoid, but not mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a, KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very low WNK4 was determined.
Conclusions: These results are consistent with a model of Cl- secretion whereby Cl- is taken up across the basolateral membrane by a Na+-K+-2Cl- cotransporter (NKCC) and potentially another transporter, is secreted across the apical membrane via a Cl- channel, likely CFTR, and demonstrate the regulation of Cl- secretion by protein kinase A and glucocorticoids.
{"title":"cAMP-stimulated Cl- secretion is increased by glucocorticoids and inhibited by bumetanide in semicircular canal duct epithelium.","authors":"Satyanarayana R Pondugula, Suresh B Kampalli, Tao Wu, Robert C De Lisle, Nithya N Raveendran, Donald G Harbidge, Daniel C Marcus","doi":"10.1186/1472-6793-13-6","DOIUrl":"https://doi.org/10.1186/1472-6793-13-6","url":null,"abstract":"<p><strong>Background: </strong>The vestibular system controls the ion composition of its luminal fluid through several epithelial cell transport mechanisms under hormonal regulation. The semicircular canal duct (SCCD) epithelium has been shown to secrete Cl- under β2-adrenergic stimulation. In the current study, we sought to determine the ion transporters involved in Cl- secretion and whether secretion is regulated by PKA and glucocorticoids.</p><p><strong>Results: </strong>Short circuit current (Isc) from rat SCCD epithelia demonstrated stimulation by forskolin (EC50: 0.8 μM), 8-Br-cAMP (EC50: 180 μM), 8-pCPT-cAMP (100 μM), IBMX (250 μM), and RO-20-1724 (100 μM). The PKA activator N6-BNZ-cAMP (0.1, 0.3 & 1 mM) also stimulated Isc. Partial inhibition of stimulated Isc individually by bumetanide (10 & 50 μM), and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 μM) were additive and complete. Stimulated Isc was also partially inhibited by CFTRinh-172 (5 & 30 μM), flufenamic acid (5 μM) and diphenylamine-2,2'-dicarboxylic acid (DPC; 1 mM). Native canals of CFTR+/- mice showed a stimulation of Isc from isoproterenol and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while canals from CFTR-/- mice had no responses. Nonetheless, CFTR-/- mice showed no difference from CFTR+/- mice in their ability to balance (rota-rod). Stimulated Isc was greater after chronic incubation (24 hr) with the glucocorticoids dexamethasone (0.1 & 0.3 μM), prednisolone (0.3, 1 & 3 μM), hydrocortisone (0.01, 0.1 & 1 μM), and corticosterone (0.1 & 1 μM) and mineralocorticoid aldosterone (1 μM). Steroid action was blocked by mifepristone but not by spironolactone, indicating all the steroids activated the glucocorticoid, but not mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a, KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very low WNK4 was determined.</p><p><strong>Conclusions: </strong>These results are consistent with a model of Cl- secretion whereby Cl- is taken up across the basolateral membrane by a Na+-K+-2Cl- cotransporter (NKCC) and potentially another transporter, is secreted across the apical membrane via a Cl- channel, likely CFTR, and demonstrate the regulation of Cl- secretion by protein kinase A and glucocorticoids.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40232475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philippe Cettour-Rose, Carole Bezençon, Christian Darimont, Johannes le Coutre, Sami Damak
Background: Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5.
Results: Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g) and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g) after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice.
Conclusion: Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.
背景:奎宁是一种天然分子,常用作汤力水的调味剂。在饮食中添加奎宁可以降低大鼠的体重和食物摄入量。奎宁是一种Trpm5的体外抑制剂,Trpm5是一种在味蕾细胞、胃肠道和胰腺中表达的阳离子通道。本研究旨在研究膳食中添加奎宁对雄性小鼠体重和体组成的影响,探讨其作用机制,以及这种影响是否通过Trpm5介导。结果:与常规均衡饮食AIN的小鼠相比,13周后,添加0.1%奎宁AIN的小鼠增重(2.89±0.30 g vs 5.39±0.50 g)和脂肪量(2.22±0.26 g vs 4.33±0.43 g)更少,血糖和血浆甘油三酯也更低。服用奎宁补充饮食的小鼠与服用对照组饮食的小鼠在食物摄取量上没有差异。Trpm5基因敲除小鼠获得的脂肪量少于野生型小鼠。饮食-基因型对体重和体重增加有相互作用的趋势,与WT背景相比,Trpm5 KO对奎宁的影响不那么明显。奎宁喂养小鼠的粪便重量、能量和脂肪含量高于常规AIN喂养小鼠,Trpm5 KO小鼠的粪便重量、能量和脂肪含量高于野生型小鼠。结论:奎宁对雄性C57BL6小鼠体重有一定的控制作用,但不影响摄食。Trpm5对奎宁依赖性体重控制有部分贡献。
{"title":"Quinine controls body weight gain without affecting food intake in male C57BL6 mice.","authors":"Philippe Cettour-Rose, Carole Bezençon, Christian Darimont, Johannes le Coutre, Sami Damak","doi":"10.1186/1472-6793-13-5","DOIUrl":"https://doi.org/10.1186/1472-6793-13-5","url":null,"abstract":"<p><strong>Background: </strong>Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5.</p><p><strong>Results: </strong>Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g) and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g) after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice.</p><p><strong>Conclusion: </strong>Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31225579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: SLC10A2-mediated reabsorption of bile acids at the distal end of the ileum is the first step in enterohepatic circulation. Because bile acids act not only as detergents but also as signaling molecules in lipid metabolism and energy production, SLC10A2 is important as the key transporter for understanding the in vivo kinetics of bile acids. SLC10A family members and the homologous genes of various species share a highly conserved region corresponding to Gly104-Pro142 of SLC10A2. The functional importance of this region has not been fully elucidated.
Results: To elucidate the functional importance of this region, we previously performed mutational analysis of the uncharged polar residues and proline in the distal one-third (Thr130-Pro142) of the highly conserved region in mouse Slc10a2. In this study, proline and uncharged polar residues in the remaining two-thirds of this region in mouse Slc10a2 were subjected to mutational analysis, and taurocholic acid uptake and cell surface localization were examined. Cell surface localization of Slc10a2 is necessary for bile acid absorption. Mutants in which Asp or Leu were substituted for Pro107 (P107N or P107L) were abundantly expressed, but their cell surface localization was impaired. The S126A mutant was completely impaired in cellular expression. The T110A and S128A mutants exhibited remarkably enhanced membrane expression. The S112A mutant was properly expressed at the cell surface but transport activity was completely lost. Replacement of Tyr117 with various amino acids resulted in reduced transport activity. The degree of reduction roughly depended on the van der Waals volume of the side chains.
Conclusions: The functional importance of proline and uncharged polar residues in the highly conserved region of mouse Slc10a2 was determined. This information will contribute to the design of bile acid-conjugated prodrugs for efficient drug delivery or SLC10A2 inhibitors for hypercholesterolemia treatment.
{"title":"Importance of uncharged polar residues and proline in the proximal two-thirds (Pro107-Ser128) of the highly conserved region of mouse ileal Na+-dependent bile acid transporter, Slc10a2, in transport activity and cellular expression.","authors":"Tohru Saeki, Kosuke Sato, Shiho Ito, Keisuke Ikeda, Ryuhei Kanamoto","doi":"10.1186/1472-6793-13-4","DOIUrl":"https://doi.org/10.1186/1472-6793-13-4","url":null,"abstract":"<p><strong>Background: </strong>SLC10A2-mediated reabsorption of bile acids at the distal end of the ileum is the first step in enterohepatic circulation. Because bile acids act not only as detergents but also as signaling molecules in lipid metabolism and energy production, SLC10A2 is important as the key transporter for understanding the in vivo kinetics of bile acids. SLC10A family members and the homologous genes of various species share a highly conserved region corresponding to Gly104-Pro142 of SLC10A2. The functional importance of this region has not been fully elucidated.</p><p><strong>Results: </strong>To elucidate the functional importance of this region, we previously performed mutational analysis of the uncharged polar residues and proline in the distal one-third (Thr130-Pro142) of the highly conserved region in mouse Slc10a2. In this study, proline and uncharged polar residues in the remaining two-thirds of this region in mouse Slc10a2 were subjected to mutational analysis, and taurocholic acid uptake and cell surface localization were examined. Cell surface localization of Slc10a2 is necessary for bile acid absorption. Mutants in which Asp or Leu were substituted for Pro107 (P107N or P107L) were abundantly expressed, but their cell surface localization was impaired. The S126A mutant was completely impaired in cellular expression. The T110A and S128A mutants exhibited remarkably enhanced membrane expression. The S112A mutant was properly expressed at the cell surface but transport activity was completely lost. Replacement of Tyr117 with various amino acids resulted in reduced transport activity. The degree of reduction roughly depended on the van der Waals volume of the side chains.</p><p><strong>Conclusions: </strong>The functional importance of proline and uncharged polar residues in the highly conserved region of mouse Slc10a2 was determined. This information will contribute to the design of bile acid-conjugated prodrugs for efficient drug delivery or SLC10A2 inhibitors for hypercholesterolemia treatment.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31208779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aline C Caetano, Lucimara F da Veiga, Flávia R Capaldi, Severino M de Alencar, Ricardo A Azevedo, Rosangela M N Bezerra
Background: Reactive oxygen species (ROS) are formed under natural physiological conditions and are thought to play an important role in many human diseases. A wide range of antioxidants are involved in cellular defense mechanisms against ROS, which can be generated in excess during stressful conditions, these include enzymes and non-enzymatic antioxidants. The aim of this study was to evaluate the antioxidant responses of mice to two diets control, commercial and the purified AIN 93 diet, commonly used in experiments with rodents.
Results: Malondialdehyde (MDA) and hydrogen peroxide (H2O2) concentrations and superoxide dismutase (SOD) and glutathione reductase (GR) activities determined in the liver were lower in the group of mice fed with the AIN 93 diet, while catalase (CAT) activity was higher in the same group, when compared to the group fed on the commercial diet. Liver glutathione peroxidase (GSH-Px) activity was similar in the groups fed on either AIN 93 or the commercial diets. Two SOD isoforms, Mn-SODII and a Cu/Zn-SODV, were specifically reduced in the liver of the AIN 93 diet fed animals.
Conclusions: The clear differences in antioxidant responses observed in the livers of mice fed on the two diets suggest that the macro- and micro-nutrient components with antioxidant properties, including vitamin E, can promote changes in the activity of enzymes involved in the removal of the ROS generated by cell metabolism.
背景:活性氧(ROS)是在自然生理条件下形成的,被认为在许多人类疾病中起着重要作用。多种抗氧化剂参与了细胞抵御 ROS 的机制,这些抗氧化剂包括酶和非酶抗氧化剂。本研究的目的是评估小鼠对两种饮食的抗氧化反应,即啮齿动物实验中常用的对照饮食、商业饮食和纯化 AIN 93 饮食:结果:与使用商品饲料喂养的小鼠相比,使用 AIN 93 饲料喂养的小鼠肝脏中丙二醛(MDA)和过氧化氢(H2O2)浓度以及超氧化物歧化酶(SOD)和谷胱甘肽还原酶(GR)活性较低,而过氧化氢酶(CAT)活性较高。肝脏谷胱甘肽过氧化物酶(GSH-Px)活性在以 AIN 93 或商品饲料喂养的组别中相似。饲喂 AIN 93 的动物肝脏中的两种 SOD 同工酶(Mn-SODII 和 Cu/Zn-SODV )明显减少:结论:在两种饲料喂养的小鼠肝脏中观察到的抗氧化反应的明显差异表明,包括维生素 E 在内的具有抗氧化特性的宏观和微观营养成分可促进参与清除细胞代谢产生的 ROS 的酶的活性发生变化。
{"title":"The antioxidant response of the liver of male Swiss mice raised on a AIN 93 or commercial diet.","authors":"Aline C Caetano, Lucimara F da Veiga, Flávia R Capaldi, Severino M de Alencar, Ricardo A Azevedo, Rosangela M N Bezerra","doi":"10.1186/1472-6793-13-3","DOIUrl":"10.1186/1472-6793-13-3","url":null,"abstract":"<p><strong>Background: </strong>Reactive oxygen species (ROS) are formed under natural physiological conditions and are thought to play an important role in many human diseases. A wide range of antioxidants are involved in cellular defense mechanisms against ROS, which can be generated in excess during stressful conditions, these include enzymes and non-enzymatic antioxidants. The aim of this study was to evaluate the antioxidant responses of mice to two diets control, commercial and the purified AIN 93 diet, commonly used in experiments with rodents.</p><p><strong>Results: </strong>Malondialdehyde (MDA) and hydrogen peroxide (H2O2) concentrations and superoxide dismutase (SOD) and glutathione reductase (GR) activities determined in the liver were lower in the group of mice fed with the AIN 93 diet, while catalase (CAT) activity was higher in the same group, when compared to the group fed on the commercial diet. Liver glutathione peroxidase (GSH-Px) activity was similar in the groups fed on either AIN 93 or the commercial diets. Two SOD isoforms, Mn-SODII and a Cu/Zn-SODV, were specifically reduced in the liver of the AIN 93 diet fed animals.</p><p><strong>Conclusions: </strong>The clear differences in antioxidant responses observed in the livers of mice fed on the two diets suggest that the macro- and micro-nutrient components with antioxidant properties, including vitamin E, can promote changes in the activity of enzymes involved in the removal of the ROS generated by cell metabolism.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31185493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}