Pub Date : 2025-03-01DOI: 10.1016/j.bbrc.2025.151546
Bao Chi Wong , Fong Yoke Ling , Qasim Ayub , Hock Siew Tan
Identifying essential genes in bacterial pathogens during infection can enhance knowledge and provide novel targets for antimicrobial agents’ development. Currently, only Shigella flexneri essential genes during in vitro growth have been experimentally identified. This study used transposon insertion sequencing (TIS) to identify Shigella sonnei essential genes during Caenorhabditis elegans infection. 498 genes were predicted to be essential in S. sonnei during growth on nutrient-rich media. Some genes previously predicted to be essential in Shigella were found non-essential in S. sonnei, such as acetyl metabolism genes (aceEF, lpdA) and sulphate transport genes (cysA, cyst, cysW). Finally, 217 genes were predicted as S. sonnei virulence genes during infection, including acid resistance and biofilm formation genes which was not linked to S. sonnei virulence previously.
{"title":"Transposon mutagenesis identifies acid resistance and biofilm genes as Shigella sonnei virulence factors in Caenorhabditis elegans infection","authors":"Bao Chi Wong , Fong Yoke Ling , Qasim Ayub , Hock Siew Tan","doi":"10.1016/j.bbrc.2025.151546","DOIUrl":"10.1016/j.bbrc.2025.151546","url":null,"abstract":"<div><div>Identifying essential genes in bacterial pathogens during infection can enhance knowledge and provide novel targets for antimicrobial agents’ development. Currently, only <em>Shigella flexneri</em> essential genes during <em>in vitro</em> growth have been experimentally identified<em>.</em> This study used transposon insertion sequencing (TIS) to identify <em>Shigella sonnei</em> essential genes during <em>Caenorhabditis elegans</em> infection. 498 genes were predicted to be essential in <em>S. sonnei</em> during growth on nutrient-rich media. Some genes previously predicted to be essential in <em>Shigella</em> were found non-essential in <em>S. sonnei,</em> such as acetyl metabolism genes (<em>aceEF, lpdA</em>) and sulphate transport genes (<em>cysA, cyst, cysW</em>). Finally, 217 genes were predicted as <em>S. sonnei</em> virulence genes during infection, including acid resistance and biofilm formation genes which was not linked to <em>S. sonnei</em> virulence previously.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151546"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.bbrc.2025.151557
Dan Huang , Cheng-Yu Lou , Ya-Lan Yu , Li Fang
This study aims to investigate the role of nucleolin in the proliferation of vascular smooth muscle cells (VSMCs) and the underlying molecular mechanism, with a focus on protein-mRNA interactions. Various methods, including BrdU labeling, protein quantification, and CCK-8 cell proliferation assay, were employed to assess the effects of VSMCs proliferation induced by angiotensin II (Ang II) as well as the expressions of TGF-β1 and VEGF at the mRNA and protein levels. Gene transfection, RNA interference, and nucleolin mutant (Nucl-309) were utilized to examine the regulatory impact of nucleolin on the expression and the stability of the TGF-β1 and VEGF mRNA. Additionally, immunoprecipitation, RNA-EMSA, and luciferase reporter gene assays were conducted to investigate the binding of nucleolin to the 3′ UTR of the TGF-β1 and VEGF mRNA. It was found that Ang II increased the DNA synthesis capacity, total cell protein content, and cell survival rate of VSMCs, and the expressions of TGF-β1 and VEGF gradually increased upon stimulation by Ang II. Nucleolin overexpression and knockdown significantly enhanced and inhibited the expressions of TGF-β1 and VEGF, respectively. The overexpression of the nucleolin mutant showed no regulatory effect on the expressions of TGF-β1 and VEGF. The interaction between nucleolin and the 3′ UTR of the TGF-β1 and VEGF mRNA increased their stability and boosted their expressions. Hence, nucleolin plays a key role in promoting Ang II-induced VSMCs proliferation by enhancing the stability of the TGF-β1 and VEGF mRNA through binding to their respective 3′ UTR, which ultimately upregulates their protein expression.
{"title":"The RNA-binding protein nucleolin mediates the pro-proliferative effect of angiotensin II for vascular smooth muscle cells through the post-transcriptional regulation of TGF-β1 and VEGF expression","authors":"Dan Huang , Cheng-Yu Lou , Ya-Lan Yu , Li Fang","doi":"10.1016/j.bbrc.2025.151557","DOIUrl":"10.1016/j.bbrc.2025.151557","url":null,"abstract":"<div><div>This study aims to investigate the role of nucleolin in the proliferation of vascular smooth muscle cells (VSMCs) and the underlying molecular mechanism, with a focus on protein-mRNA interactions. Various methods, including BrdU labeling, protein quantification, and CCK-8 cell proliferation assay, were employed to assess the effects of VSMCs proliferation induced by angiotensin II (Ang II) as well as the expressions of TGF-β1 and VEGF at the mRNA and protein levels. Gene transfection, RNA interference, and nucleolin mutant (Nucl-309) were utilized to examine the regulatory impact of nucleolin on the expression and the stability of the TGF-β1 and VEGF mRNA. Additionally, immunoprecipitation, RNA-EMSA, and luciferase reporter gene assays were conducted to investigate the binding of nucleolin to the 3′ UTR of the TGF-β1 and VEGF mRNA. It was found that Ang II increased the DNA synthesis capacity, total cell protein content, and cell survival rate of VSMCs, and the expressions of TGF-β1 and VEGF gradually increased upon stimulation by Ang II. Nucleolin overexpression and knockdown significantly enhanced and inhibited the expressions of TGF-β1 and VEGF, respectively. The overexpression of the nucleolin mutant showed no regulatory effect on the expressions of TGF-β1 and VEGF. The interaction between nucleolin and the 3′ UTR of the TGF-β1 and VEGF mRNA increased their stability and boosted their expressions. Hence, nucleolin plays a key role in promoting Ang II-induced VSMCs proliferation by enhancing the stability of the TGF-β1 and VEGF mRNA through binding to their respective 3′ UTR, which ultimately upregulates their protein expression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151557"},"PeriodicalIF":2.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/j.bbrc.2025.151551
Qingpeng Sun , Chao Zhang , Guanyu Hu , Ke Zhu , Sheng Zheng
Albiflorin (ALB) has been shown to promote osteogenesis, however, its effect on angiogenesis still remains unclear. This research aimed to explore the effect of ALB on angiogenesis and bone regeneration under osteoporotic conditions. The pro-osteogenesis capacity of ALB was assessed by osteogenic differentiation assays. Subsequent research examined the effect of ALB on angiogenesis. After revealing the pro-angiogenesis capacity of ALB, we explored the relationship between the pro-osteogenesis capacity and the pro-angiogenesis capacity of ALB by angiogenesis-related assays. Whereafter, the osteoporotic bone defect rat model was constructed to explore the effect of ALB on osteoporotic bone regeneration. Our research found that ALB promoted osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and enhanced the expression of angiogenesis-specific markers, but it couldn't promote angiogenesis of human umbilical vein endothelial cells (HUVECs) directly. Further research revealed that ALB enhanced HUVECs migration and tube formation when the cells cultured in BMSCs-conditioned medium. Subsequently, it is observed that ALB facilitated bone regeneration under osteoporotic conditions by promoting osteogenesis and the formation of CD31hiEMCNhi type H-positive vessels. To sum up, this research indicated that ALB could improve osteoporotic bone regeneration by promoting osteogenesis-angiogenesis coupling of BMSCs, which provided a novel perspective for improving osteoporotic bone regeneration.
{"title":"Albiflorin improves osteoporotic bone regeneration by promoting osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells","authors":"Qingpeng Sun , Chao Zhang , Guanyu Hu , Ke Zhu , Sheng Zheng","doi":"10.1016/j.bbrc.2025.151551","DOIUrl":"10.1016/j.bbrc.2025.151551","url":null,"abstract":"<div><div>Albiflorin (ALB) has been shown to promote osteogenesis, however, its effect on angiogenesis still remains unclear. This research aimed to explore the effect of ALB on angiogenesis and bone regeneration under osteoporotic conditions. The pro-osteogenesis capacity of ALB was assessed by osteogenic differentiation assays. Subsequent research examined the effect of ALB on angiogenesis. After revealing the pro-angiogenesis capacity of ALB, we explored the relationship between the pro-osteogenesis capacity and the pro-angiogenesis capacity of ALB by angiogenesis-related assays. Whereafter, the osteoporotic bone defect rat model was constructed to explore the effect of ALB on osteoporotic bone regeneration. Our research found that ALB promoted osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and enhanced the expression of angiogenesis-specific markers, but it couldn't promote angiogenesis of human umbilical vein endothelial cells (HUVECs) directly. Further research revealed that ALB enhanced HUVECs migration and tube formation when the cells cultured in BMSCs-conditioned medium. Subsequently, it is observed that ALB facilitated bone regeneration under osteoporotic conditions by promoting osteogenesis and the formation of CD31<sup>hi</sup>EMCN<sup>hi</sup> type H-positive vessels. To sum up, this research indicated that ALB could improve osteoporotic bone regeneration by promoting osteogenesis-angiogenesis coupling of BMSCs, which provided a novel perspective for improving osteoporotic bone regeneration.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151551"},"PeriodicalIF":2.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our previous study found that Ca2+/calmodulin-dependent protein kinase II (CaMKII) potentiates the slow delayed rectifier K+ current (IKs) in sinoatrial node (SAN) pacemaker cells. Recently, oxidative activation of CaMKII has emerged as a major cause of SAN dysfunction; however, its correlation with IKs regulation remains unclear. In this study, we investigated the effect of hydrogen peroxide (H2O2) on IKs in SAN cells isolated from guinea pig heart. Whole-cell patch-clamp recordings were performed using an EGTA (5 mM) pipette solution to stabilize intracellular Ca2+ levels (pCa 7). The results showed that 5 min of H2O2 (100 μM) perfusion initiated an increase in IKs, which gradually increased to saturation (∼60.5 % enhancement from baseline to saturation) after 10 min of H2O2 exposure. In contrast, IKs remained almost unchanged in the presence of catalase (1000 units mL−1). These observations were replicable in atrial and ventricular cardiomyocytes. H2O2 failed to stimulate KCNQ1/KCNE1 currents in HEK and CHO cells expressing low CaMKII levels. In SAN cells, H2O2-induced IKs enhancement was strongly attenuated by intracellular dialysis with a lower Ca2+ concentration (pCa 10) or by pretreatment with KN-93 (1 μM), suggesting that Ca2+/calmodulin binding to CaMKII is a prerequisite for CaMKII activation. Autocamtide-2 inhibitory peptide (AIP, 1 μM), an inhibitor of the catalytic domain of CaMKII, almost completely abolished the H2O2-induced potentiation of IKs. Taken together, these findings imply that H2O2 enhances cardiac IKs through the oxidative activation of CaMKII.
{"title":"Involvement of CaMKII in the modulation of IKs under oxidative stress in guinea pig sinoatrial node cells","authors":"Yu Xie , Futoshi Toyoda , Weiguang Ding , Hiroshi Matsuura","doi":"10.1016/j.bbrc.2025.151554","DOIUrl":"10.1016/j.bbrc.2025.151554","url":null,"abstract":"<div><div>Our previous study found that Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) potentiates the slow delayed rectifier K<sup>+</sup> current (<em>I</em><sub>Ks</sub>) in sinoatrial node (SAN) pacemaker cells. Recently, oxidative activation of CaMKII has emerged as a major cause of SAN dysfunction; however, its correlation with <em>I</em><sub>Ks</sub> regulation remains unclear. In this study, we investigated the effect of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) on <em>I</em><sub>Ks</sub> in SAN cells isolated from guinea pig heart. Whole-cell patch-clamp recordings were performed using an EGTA (5 mM) pipette solution to stabilize intracellular Ca<sup>2+</sup> levels (pCa 7). The results showed that 5 min of H<sub>2</sub>O<sub>2</sub> (100 μM) perfusion initiated an increase in <em>I</em><sub>Ks</sub>, which gradually increased to saturation (∼60.5 % enhancement from baseline to saturation) after 10 min of H<sub>2</sub>O<sub>2</sub> exposure. In contrast, <em>I</em><sub>Ks</sub> remained almost unchanged in the presence of catalase (1000 units mL<sup>−1</sup>). These observations were replicable in atrial and ventricular cardiomyocytes. H<sub>2</sub>O<sub>2</sub> failed to stimulate KCNQ1/KCNE1 currents in HEK and CHO cells expressing low CaMKII levels. In SAN cells, H<sub>2</sub>O<sub>2</sub>-induced <em>I</em><sub>Ks</sub> enhancement was strongly attenuated by intracellular dialysis with a lower Ca<sup>2+</sup> concentration (pCa 10) or by pretreatment with KN-93 (1 μM), suggesting that Ca<sup>2+</sup>/calmodulin binding to CaMKII is a prerequisite for CaMKII activation. Autocamtide-2 inhibitory peptide (AIP, 1 μM), an inhibitor of the catalytic domain of CaMKII, almost completely abolished the H<sub>2</sub>O<sub>2</sub>-induced potentiation of <em>I</em><sub>Ks</sub>. Taken together, these findings imply that H<sub>2</sub>O<sub>2</sub> enhances cardiac <em>I</em><sub>Ks</sub> through the oxidative activation of CaMKII.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151554"},"PeriodicalIF":2.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/j.bbrc.2025.151537
Xin Ji , Qianqian Dong , Wanqiu Li , Wei Luo , Ning Zhou , Hanzhao Li , Xiaolong Yang
Atherosclerotic cardiovascular diseases can lead to myocardial infarction and stroke, which are linked to elevated rates of mortality. Morin is a flavonoid compound that can be extracted from mulberries and possesses anti-inflammatory and antioxidant properties. The objective of this research is to elucidate Morin's impact on atherosclerosis. The ApoE−/− mice were divided into three groups: control group, HFD group and HFD + Morin group. The mice in control group received a normal diet (ND). To create an atherosclerosis model, ApoE−/− mice were subjected to a high-fat diet (HFD) for 8 weeks. The mice were assigned to two distinct categories at random based on whether Morin intervention was administered: one serving as the HFD group and the other as the HFD + Morin group. The mice received Morin for 4 weeks at a dosage of 50 mg/kg orally in the model + Morin group. Subsequently, ORO staining assay was performed to evaluate the formation of aortic plaques. ELISA was used to measure IFN-γ and TNF-α levels in plasma of the mice. In vitro, mouse macrophages RAW264.7 were cultured and treated with IFN-γ for 24 h, followed by Morin treatment for another 24 h. Western blotting was conducted to analyze changes in macrophage polarization markers CD86 and CD206, as well as P-STAT1 levels. DCFH-DA was used to detect changes in intracellular ROS levels. Subsequently, RAW264.7 cells were treated with the STAT1 inhibitor Lenvatinib to further investigate changes in CD86 and CD206, as well as ROS levels. In vivo data showed that Morin markedly diminished the size of aortic plaques and suppressed the secretion of IFN-γ and TNF-α. In vitro data indicated that Morin reduced M1 polarization and intracellular ROS levels through inhibiting the STAT1 pathway activation in RAW264.7 cells, ultimately suppressing inflammation.
{"title":"The role of Morin in attenuating atherosclerosis via STAT1 pathway inhibition","authors":"Xin Ji , Qianqian Dong , Wanqiu Li , Wei Luo , Ning Zhou , Hanzhao Li , Xiaolong Yang","doi":"10.1016/j.bbrc.2025.151537","DOIUrl":"10.1016/j.bbrc.2025.151537","url":null,"abstract":"<div><div>Atherosclerotic cardiovascular diseases can lead to myocardial infarction and stroke, which are linked to elevated rates of mortality. Morin is a flavonoid compound that can be extracted from mulberries and possesses anti-inflammatory and antioxidant properties. The objective of this research is to elucidate Morin's impact on atherosclerosis. The ApoE<sup>−/−</sup> mice were divided into three groups: control group, HFD group and HFD + Morin group. The mice in control group received a normal diet (ND). To create an atherosclerosis model, ApoE<sup>−/−</sup> mice were subjected to a high-fat diet (HFD) for 8 weeks. The mice were assigned to two distinct categories at random based on whether Morin intervention was administered: one serving as the HFD group and the other as the HFD + Morin group. The mice received Morin for 4 weeks at a dosage of 50 mg/kg orally in the model + Morin group. Subsequently, ORO staining assay was performed to evaluate the formation of aortic plaques. ELISA was used to measure IFN-γ and TNF-α levels in plasma of the mice. <em>In vitro</em>, mouse macrophages RAW264.7 were cultured and treated with IFN-γ for 24 h, followed by Morin treatment for another 24 h. Western blotting was conducted to analyze changes in macrophage polarization markers CD86 and CD206, as well as P-STAT1 levels. DCFH-DA was used to detect changes in intracellular ROS levels. Subsequently, RAW264.7 cells were treated with the STAT1 inhibitor Lenvatinib to further investigate changes in CD86 and CD206, as well as ROS levels. In vivo data showed that Morin markedly diminished the size of aortic plaques and suppressed the secretion of IFN-γ and TNF-α. In vitro data indicated that Morin reduced M1 polarization and intracellular ROS levels through inhibiting the STAT1 pathway activation in RAW264.7 cells, ultimately suppressing inflammation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151537"},"PeriodicalIF":2.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/j.bbrc.2025.151508
Zhongxing Liang, Xuehai Bian, Hyunsuk Shim
{"title":"Corrigendum to \"Downregulation of microRNA-206 promotes invasion and angiogenesis of triple negative breast cancer\" [Biochem. Biophys. Res. Commun. 477 (3) (2016) 461-466].","authors":"Zhongxing Liang, Xuehai Bian, Hyunsuk Shim","doi":"10.1016/j.bbrc.2025.151508","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151508","url":null,"abstract":"","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":" ","pages":"151508"},"PeriodicalIF":2.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.bbrc.2025.151529
Laura Bordoni, Irene Petracci, Rosita Gabbianelli
Emerging evidence highlights conflicting data regarding the roles of trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) plasma levels in cardiovascular diseases. In this study, we investigate in THP-1 monocytes the pro-inflammatory effects of TMA and TMAO at both physiological and pathological concentrations previously measured in a human cohort, focusing on their impact on ATP production, mitochondrial gene expression, mitochondrial membrane potential (ΔΨm), and mitochondrial DNA copy number (mtDNAcn). Results show that 0.6 μM and 1.2 μM TMA as well as 40 μM TMAO increase the expression levels of the pro-inflammatory IL-8, while the anti-inflammatory cytokine IL-10 was upregulated by 1.2 μM TMA and 40 μM TMAO. An increase in the expression levels of mitochondrial genes MT-ATP6, MT-CO1, MT-CYB and MT-ND6 was measured on all conditions tested, while no significant changes in mtDNAcn were observed. Remarkably, TMA (0.6 μM and 1.2 μM), but not TMAO, decreases ATP content and increases the mitochondrial membrane potential in THP-1 cells after 24 h of incubation. In conclusion, our study suggests that not only circulating TMAO but also TMA may contribute to vascular inflammation by disturbing mitochondrial functions in monocytes. This evidence underscores the need for further investigations to better understand the effects of these metabolites on cardiovascular health.
{"title":"TMA, beyond TMAO, might contribute to vascular inflammation by disturbing mitochondrial functions in macrophages","authors":"Laura Bordoni, Irene Petracci, Rosita Gabbianelli","doi":"10.1016/j.bbrc.2025.151529","DOIUrl":"10.1016/j.bbrc.2025.151529","url":null,"abstract":"<div><div>Emerging evidence highlights conflicting data regarding the roles of trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) plasma levels in cardiovascular diseases. In this study, we investigate in THP-1 monocytes the pro-inflammatory effects of TMA and TMAO at both physiological and pathological concentrations previously measured in a human cohort, focusing on their impact on ATP production, mitochondrial gene expression, mitochondrial membrane potential (ΔΨm), and mitochondrial DNA copy number (mtDNAcn). Results show that 0.6 μM and 1.2 μM TMA as well as 40 μM TMAO increase the expression levels of the pro-inflammatory IL-8, while the anti-inflammatory cytokine IL-10 was upregulated by 1.2 μM TMA and 40 μM TMAO. An increase in the expression levels of mitochondrial genes <em>MT-ATP6</em>, <em>MT-CO1</em>, <em>MT-CYB</em> and <em>MT-ND6</em> was measured on all conditions tested, while no significant changes in mtDNAcn were observed. Remarkably, TMA (0.6 μM and 1.2 μM), but not TMAO, decreases ATP content and increases the mitochondrial membrane potential in THP-1 cells after 24 h of incubation. In conclusion, our study suggests that not only circulating TMAO but also TMA may contribute to vascular inflammation by disturbing mitochondrial functions in monocytes. This evidence underscores the need for further investigations to better understand the effects of these metabolites on cardiovascular health.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151529"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.bbrc.2025.151535
Chunxia Shi, Yukun Wang, Jin Guo, Danmei Zhang, Yanqiong Zhang, Xiaoya Zhang, Zuojiong Gong
Malate dehydrogenase 1 (MDH1) and isocitrate dehydrogenase 1 (IDH1) are two crucial enzymes in the process of energy metabolism. MDH1 plays a crucial role in the malate-aspartate shuttle in the cytoplasm by utilizing the coenzyme NAD/NADH to catalyze the interconversion of malate and oxaloacetate. IDH1 utilizes the coenzyme NADP/NADPH to facilitate the reciprocal transformation between isocitrate and α-ketoglutarate and plays a significant role in the metabolic processes of carbohydrates, lipids, and proteins in the liver. MDH1 and IDH1, along with their posttranslational modifications such as methylation and acetylation can influence the development of many diseases. This article reviews the function of MDH1, IDH1, and their posttranslational changes in various illnesses, aiming to offer new perspectives on disease diagnosis and therapy.
{"title":"Role of malate dehydrogenase 1 and isocitrate dehydrogenase 1 and their posttranslational modifications in diseases","authors":"Chunxia Shi, Yukun Wang, Jin Guo, Danmei Zhang, Yanqiong Zhang, Xiaoya Zhang, Zuojiong Gong","doi":"10.1016/j.bbrc.2025.151535","DOIUrl":"10.1016/j.bbrc.2025.151535","url":null,"abstract":"<div><div>Malate dehydrogenase 1 (MDH1) and isocitrate dehydrogenase 1 (IDH1) are two crucial enzymes in the process of energy metabolism. MDH1 plays a crucial role in the malate-aspartate shuttle in the cytoplasm by utilizing the coenzyme NAD/NADH to catalyze the interconversion of malate and oxaloacetate. IDH1 utilizes the coenzyme NADP/NADPH to facilitate the reciprocal transformation between isocitrate and α-ketoglutarate and plays a significant role in the metabolic processes of carbohydrates, lipids, and proteins in the liver. MDH1 and IDH1, along with their posttranslational modifications such as methylation and acetylation can influence the development of many diseases. This article reviews the function of MDH1, IDH1, and their posttranslational changes in various illnesses, aiming to offer new perspectives on disease diagnosis and therapy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151535"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
1-O-Alkylglycerol (AKG), a lipid characteristic of marine organisms, possesses an ether-linked alkyl chain on its glycerol backbone. AKG exhibits various biological activities, including anti-cancer effects, promoting sperm motility, and stimulating immune response. Metabolically, AKG is converted into alkyl- and alkenyl-phospholipids (PLs), which are key components of the cell membrane and play essential roles in maintaining membrane homeostasis and cellular functions. However, the influence of AKG on myogenesis and ether-type PL metabolism in muscle cells remains unknown. This study evaluated the effects of AKG on myogenic differentiation and ether-PL metabolism in mouse C2C12 myoblasts. During differentiation, cells were treated with 10–20 μM 1-O-octadecyl-glycerol (batyl alcohol) and 1-O-hexadecyl-glycerol (chimyl alcohol). By day 7 of differentiation, myotube size had increased in cells treated with AKGs. Comparative tests using compounds with similar or partial structures, including monoacylglycerol and alkenylglycerol, demonstrated that this activity was linked to the structural features of AKG. Conversely, myotube growth was insufficient after treatment with 1-O-dodecyl-glycerol, which contains a shorter alkyl chain. Additionally, batyl alcohol treatment elevated the levels of ether-phosphatidylcholine (PC) molecular species, including e-PC38:4 and e-PC38:5, those are presumed to bind polyunsaturated fatty acids. Chimyl alcohol treatment also increased ether-PC species, including e-PC36:4 and e-PC36:5 while monoacylglycerol did not alter ether-PC levels. These findings suggest that AKG plays a crucial role in membrane dynamics during myogenesis through metabolic conversion to ether-PLs, providing novel insights into muscle homeostasis to contribute to developing nutritional strategies and preventing and treating muscle diseases.
{"title":"Alkylglycerol enhances myogenesis and regulates ether-phospholipid metabolism in C2C12 myoblasts","authors":"Takero Sasaki, Miu Kameyama, Naoki Takatani, Masashi Hosokawa, Fumiaki Beppu","doi":"10.1016/j.bbrc.2025.151532","DOIUrl":"10.1016/j.bbrc.2025.151532","url":null,"abstract":"<div><div>1-<em>O</em>-Alkylglycerol (AKG), a lipid characteristic of marine organisms, possesses an ether-linked alkyl chain on its glycerol backbone. AKG exhibits various biological activities, including anti-cancer effects, promoting sperm motility, and stimulating immune response. Metabolically, AKG is converted into alkyl- and alkenyl-phospholipids (PLs), which are key components of the cell membrane and play essential roles in maintaining membrane homeostasis and cellular functions. However, the influence of AKG on myogenesis and ether-type PL metabolism in muscle cells remains unknown. This study evaluated the effects of AKG on myogenic differentiation and ether-PL metabolism in mouse C2C12 myoblasts. During differentiation, cells were treated with 10–20 μM 1-<em>O</em>-octadecyl-glycerol (batyl alcohol) and 1-<em>O</em>-hexadecyl-glycerol (chimyl alcohol). By day 7 of differentiation, myotube size had increased in cells treated with AKGs. Comparative tests using compounds with similar or partial structures, including monoacylglycerol and alkenylglycerol, demonstrated that this activity was linked to the structural features of AKG. Conversely, myotube growth was insufficient after treatment with 1-<em>O</em>-dodecyl-glycerol, which contains a shorter alkyl chain. Additionally, batyl alcohol treatment elevated the levels of ether-phosphatidylcholine (PC) molecular species, including e-PC38:4 and e-PC38:5, those are presumed to bind polyunsaturated fatty acids. Chimyl alcohol treatment also increased ether-PC species, including e-PC36:4 and e-PC36:5 while monoacylglycerol did not alter ether-PC levels. These findings suggest that AKG plays a crucial role in membrane dynamics during myogenesis through metabolic conversion to ether-PLs, providing novel insights into muscle homeostasis to contribute to developing nutritional strategies and preventing and treating muscle diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151532"},"PeriodicalIF":2.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gallbladder cancer (GBC) is a highly aggressive malignancy exhibiting a correlation between increased body mass index and increased risk of developing GBC. In obese individuals, the release of free fatty acids from the adipose tissue into the circulating blood is augmented. However, the role of oleic acid (OA), one of the most abundant monounsaturated fatty acids in the plasma, in GBC cell proliferation has not been determined. In this study, we investigated the effects of OA on the proliferation of GBC cells. We focused on the role of G protein-coupled receptor 120/free fatty acid receptor 4 (GPR120/FFAR4) and G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which have a high affinity for long-chain fatty acids. OA significantly promoted the proliferation of human GBC cell lines (G-415 and GBC-SD) in vitro, with the highest increase observed at 200 μM OA. In vivo, OA-treated nude mice bearing G-415 xenografts exhibited enhanced tumor growth compared to controls. Immunohistochemical analysis revealed the expression of GPR120 and GPR40 in cultured GBC cells and patient tissues. OA-induced proliferation was mediated by GPR120, as evident from significantly reduced cell proliferation upon GPR120 silencing or inhibition, and no effect of GPR40 inhibition. Furthermore, OA-induced GPR120 activation enhanced ERK phosphorylation, implicating the GPR120/ERK signaling pathway in GBC cell growth. To our knowledge, this is the first study to elucidate the role of OA in GBC cell proliferation via GPR120, suggesting its potential as a therapeutic target for GBC treatment.
{"title":"Oleic acid enhances the proliferation of gallbladder cancer cells via the GPR120/ERK pathway","authors":"Yuki Sawai , Michiyo Hayakawa , Hiroaki Yasuda , Ryuta Nakao , Takehiro Ogata , Akihiro Nakamura , Kentaro Mochizuki , Tomoki Takata , Hayato Miyake , Yoshio Sogame , Ryo Morimura , Toshihiro Kurahashi , Ping Dai , Eiichi Konishi , Yoshito Itoh , Hideo Tanaka , Yoshinori Harada","doi":"10.1016/j.bbrc.2025.151530","DOIUrl":"10.1016/j.bbrc.2025.151530","url":null,"abstract":"<div><div>Gallbladder cancer (GBC) is a highly aggressive malignancy exhibiting a correlation between increased body mass index and increased risk of developing GBC. In obese individuals, the release of free fatty acids from the adipose tissue into the circulating blood is augmented. However, the role of oleic acid (OA), one of the most abundant monounsaturated fatty acids in the plasma, in GBC cell proliferation has not been determined. In this study, we investigated the effects of OA on the proliferation of GBC cells. We focused on the role of G protein-coupled receptor 120/free fatty acid receptor 4 (GPR120/FFAR4) and G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which have a high affinity for long-chain fatty acids. OA significantly promoted the proliferation of human GBC cell lines (G-415 and GBC-SD) <em>in vitro</em>, with the highest increase observed at 200 μM OA. <em>In vivo</em>, OA-treated nude mice bearing G-415 xenografts exhibited enhanced tumor growth compared to controls. Immunohistochemical analysis revealed the expression of GPR120 and GPR40 in cultured GBC cells and patient tissues. OA-induced proliferation was mediated by GPR120, as evident from significantly reduced cell proliferation upon GPR120 silencing or inhibition, and no effect of GPR40 inhibition. Furthermore, OA-induced GPR120 activation enhanced ERK phosphorylation, implicating the GPR120/ERK signaling pathway in GBC cell growth. To our knowledge, this is the first study to elucidate the role of OA in GBC cell proliferation via GPR120, suggesting its potential as a therapeutic target for GBC treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151530"},"PeriodicalIF":2.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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