Pub Date : 2024-09-19DOI: 10.1016/j.bbrep.2024.101827
Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating GDAP1 expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the GDAP1 gene inhibits its activity. Treating cells with low GDAP1 expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the GDAP1 promoter. Thus, we identified a mechanism that could be used to manipulate GDAP1 expression.
{"title":"Epigenetic regulation of the human GDAP1 gene","authors":"","doi":"10.1016/j.bbrep.2024.101827","DOIUrl":"10.1016/j.bbrep.2024.101827","url":null,"abstract":"<div><p>Mutations in the ganglioside-induced differentiation-associated protein 1 (<em>GDAP1</em>) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating <em>GDAP1</em> expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the <em>GDAP1</em> gene inhibits its activity. Treating cells with low <em>GDAP1</em> expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the <em>GDAP1</em> promoter. Thus, we identified a mechanism that could be used to manipulate <em>GDAP1</em> expression.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001912/pdfft?md5=f9fd08807cb4fb17253e8d0588917795&pid=1-s2.0-S2405580824001912-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239098","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}
Pub Date : 2024-09-17DOI: 10.1016/j.bbrep.2024.101826
Alveolar macrophages are pivotal components of the lung's innate immune defense against respiratory virus infections. Their multifaceted role spans from viral clearance to modulation of immune responses, making them essential players in shaping disease outcomes. In this comprehensive review collection, we look into the intricate interplay between Alveolar macrophages and various respiratory viruses, shedding light on their dynamic contributions to immune resilience. From influenza to respiratory syncytial virus, Alveolar macrophages emerge as sentinels of the airways, actively participating in viral detection and initiating rapid antiviral responses. Their ability to recognize viral pathogens triggers a cascade of events, including cytokine and chemokine production that guides the recruitment and activation of immune effectors. Furthermore, Alveolar macrophages impact the fate of adaptive immune responses by modulating the activation of T lymphocytes and the secretion of key cytokines. These reviews encompass a range of insights, including the regulation of inflammasome activation, the influence of Alveolar macrophages on cytokine dysregulation, and their role in preventing secondary bacterial pneumonia post-infection. Collectively, they highlight the significance of Alveolar macrophages in preserving pulmonary integrity and immune homeostasis during viral challenges.
肺泡巨噬细胞是肺部先天性免疫防御呼吸道病毒感染的关键组成部分。它们的作用是多方面的,从清除病毒到调节免疫反应,使它们成为影响疾病结果的重要角色。在这本综合综述集中,我们将探讨肺泡巨噬细胞与各种呼吸道病毒之间错综复杂的相互作用,揭示它们对免疫复原力的动态贡献。从流感到呼吸道合胞病毒,肺泡巨噬细胞成为呼吸道的哨兵,积极参与病毒检测并启动快速抗病毒反应。它们识别病毒病原体的能力会引发一系列事件,包括细胞因子和趋化因子的产生,从而引导免疫效应因子的招募和激活。此外,肺泡巨噬细胞通过调节 T 淋巴细胞的活化和关键细胞因子的分泌,影响适应性免疫反应的命运。这些综述涵盖了一系列见解,包括炎性体活化的调控、肺泡巨噬细胞对细胞因子失调的影响以及它们在预防感染后继发性细菌性肺炎中的作用。总之,这些综述强调了肺泡巨噬细胞在病毒挑战期间维护肺部完整性和免疫平衡的重要性。
{"title":"The role of alveolar macrophages in viral respiratory infections and their therapeutic implications","authors":"","doi":"10.1016/j.bbrep.2024.101826","DOIUrl":"10.1016/j.bbrep.2024.101826","url":null,"abstract":"<div><p>Alveolar macrophages are pivotal components of the lung's innate immune defense against respiratory virus infections. Their multifaceted role spans from viral clearance to modulation of immune responses, making them essential players in shaping disease outcomes. In this comprehensive review collection, we look into the intricate interplay between Alveolar macrophages and various respiratory viruses, shedding light on their dynamic contributions to immune resilience. From influenza to respiratory syncytial virus, Alveolar macrophages emerge as sentinels of the airways, actively participating in viral detection and initiating rapid antiviral responses. Their ability to recognize viral pathogens triggers a cascade of events, including cytokine and chemokine production that guides the recruitment and activation of immune effectors. Furthermore, Alveolar macrophages impact the fate of adaptive immune responses by modulating the activation of T lymphocytes and the secretion of key cytokines. These reviews encompass a range of insights, including the regulation of inflammasome activation, the influence of Alveolar macrophages on cytokine dysregulation, and their role in preventing secondary bacterial pneumonia post-infection. Collectively, they highlight the significance of Alveolar macrophages in preserving pulmonary integrity and immune homeostasis during viral challenges.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001900/pdfft?md5=b06597a378506d5f191363dedadffbb0&pid=1-s2.0-S2405580824001900-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239096","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}
Pub Date : 2024-09-16DOI: 10.1016/j.bbrep.2024.101825
Bovine viral diarrhea (BVD) is one of the most important diseases in livestock, caused by BVD virus (BVDV). During the pathogenesis of the virus, many interactions occur between host and viral proteins. Studying these interactions can help better understand the pathogenesis of the virus, identify putative functional proteins, and find new treatment and prevention strategies. To this aim, a BVDV-host protein-protein interaction (PPI) network map was constructed using Cytoscape and analyzed with cytoHubba, Kyoto Encyclopedia of Genes and Genomics (KEGG), Gene Ontology (GO), and Protein Analysis Through Evolutionary Relationships (PANTHER). Npro with 125 connections had the greatest number of interactions with host proteins. CD46, EEF-2, and TXN genes were detected as hub genes using different ranking algorithms in cytoHubba. BVDV interactions with its host mainly focus on targeting translation, protein synthesis, and cellular metabolism pathways. Different classes of proteins including translational proteins, nucleic acid metabolism proteins, metabolite interconversion enzymes, and protein-modifying enzymes are affected by BVDV. These findings improve our understanding of the effects of the virus on the cell. Hub genes and key pathways identified in the present study can serve as targets for novel BVDV prevention or treatment strategies.
{"title":"Exogenous interactome analysis of bovine viral diarrhea virus-host using network based-approach and identification of hub genes and important pathways involved in virus pathogenesis","authors":"","doi":"10.1016/j.bbrep.2024.101825","DOIUrl":"10.1016/j.bbrep.2024.101825","url":null,"abstract":"<div><p>Bovine viral diarrhea (BVD) is one of the most important diseases in livestock, caused by BVD virus (BVDV). During the pathogenesis of the virus, many interactions occur between host and viral proteins. Studying these interactions can help better understand the pathogenesis of the virus, identify putative functional proteins, and find new treatment and prevention strategies. To this aim, a BVDV-host protein-protein interaction (PPI) network map was constructed using Cytoscape and analyzed with cytoHubba, Kyoto Encyclopedia of Genes and Genomics (KEGG), Gene Ontology (GO), and Protein Analysis Through Evolutionary Relationships (PANTHER). N<sub>pro</sub> with 125 connections had the greatest number of interactions with host proteins. <em>CD46</em>, <em>EEF</em>-2, and <em>TXN</em> genes were detected as hub genes using different ranking algorithms in cytoHubba. BVDV interactions with its host mainly focus on targeting translation, protein synthesis, and cellular metabolism pathways. Different classes of proteins including translational proteins, nucleic acid metabolism proteins, metabolite interconversion enzymes, and protein-modifying enzymes are affected by BVDV. These findings improve our understanding of the effects of the virus on the cell. Hub genes and key pathways identified in the present study can serve as targets for novel BVDV prevention or treatment strategies.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001894/pdfft?md5=6c9ef034d78f7d1328f85fc1eb4ce223&pid=1-s2.0-S2405580824001894-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239097","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}
Pub Date : 2024-09-07DOI: 10.1016/j.bbrep.2024.101824
Leukocyte migration is an essential function of innate and adaptive immune responses. Chemokines and their receptors control the migration system. The abundance of chemokines is controlled by atypical chemokine receptors (ACKRs), chemokine receptor-like molecules that do not couple to the G protein signaling pathways. Among them, ACKR4 regulates dendritic cell migration by controlling the ligands and is involved in tumor development in mouse models. Because no anti-mouse ACKR4 (mACKR4) monoclonal antibody (mAb) for flow cytometry has been reported, this study aimed to develop a novel mAb for mACKR4. Among the established anti-mACKR4 mAbs, A4Mab-1 (rat IgG2b, kappa), A4Mab-2 (rat IgG2b, kappa), and A4Mab-3 (rat IgG2b, kappa) recognized mACKR4-overexpressed Chinese hamster ovary-K1 (CHO/mACKR4) by flow cytometry. The dissociation constant (KD) values of A4Mab-1, A4Mab-2, and A4Mab-3 for CHO/mACKR4 were determined as 6.0 × 10−9 M, 1.3 × 10−8 M, and 1.7 × 10−9 M, respectively. Furthermore, A4Mab-1 and A4Mab-2 could detect mACKR4 by western blotting. These results indicated that A4Mab-1, A4Mab-2, and A4Mab-3 help to detect mACKR4 by flow cytometry and western blotting and obtain the proof of concept in preclinical models.
{"title":"Development of specific anti-mouse atypical chemokine receptor 4 monoclonal antibodies","authors":"","doi":"10.1016/j.bbrep.2024.101824","DOIUrl":"10.1016/j.bbrep.2024.101824","url":null,"abstract":"<div><p>Leukocyte migration is an essential function of innate and adaptive immune responses. Chemokines and their receptors control the migration system. The abundance of chemokines is controlled by atypical chemokine receptors (ACKRs), chemokine receptor-like molecules that do not couple to the G protein signaling pathways. Among them, ACKR4 regulates dendritic cell migration by controlling the ligands and is involved in tumor development in mouse models. Because no anti-mouse ACKR4 (mACKR4) monoclonal antibody (mAb) for flow cytometry has been reported, this study aimed to develop a novel mAb for mACKR4. Among the established anti-mACKR4 mAbs, A<sub>4</sub>Mab-1 (rat IgG<sub>2b</sub>, kappa), A<sub>4</sub>Mab-2 (rat IgG<sub>2b</sub>, kappa), and A<sub>4</sub>Mab-3 (rat IgG<sub>2b</sub>, kappa) recognized mACKR4-overexpressed Chinese hamster ovary-K1 (CHO/mACKR4) by flow cytometry. The dissociation constant (<em>K</em><sub>D</sub>) values of A<sub>4</sub>Mab-1, A<sub>4</sub>Mab-2, and A<sub>4</sub>Mab-3 for CHO/mACKR4 were determined as 6.0 × 10<sup>−9</sup> M, 1.3 × 10<sup>−8</sup> M, and 1.7 × 10<sup>−9</sup> M, respectively. Furthermore, A<sub>4</sub>Mab-1 and A<sub>4</sub>Mab-2 could detect mACKR4 by western blotting. These results indicated that A<sub>4</sub>Mab-1, A<sub>4</sub>Mab-2, and A<sub>4</sub>Mab-3 help to detect mACKR4 by flow cytometry and western blotting and obtain the proof of concept in preclinical models.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001882/pdfft?md5=df1bec1ed4b9eaea11a06516e0feac67&pid=1-s2.0-S2405580824001882-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150194","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}
Pub Date : 2024-09-07DOI: 10.1016/j.bbrep.2024.101823
Inflammatory responses and oxidative stress damage the integrity of the blood-brain barrier (BBB), which is a primary pathological modulator of neurodegenerative diseases. Brain endothelial cells are crucial components of BBB. In the present study, the effect of oxyresveratrol on lipopolysaccharide (LPS)-induced brain endothelial (bEnd.3) cells was assessed. Our results showed that oxyresveratrol diminished protein expressions of inducible nitric oxide synthase (iNOS) and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO) production, and proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) in LPS-elicited bEnd.3 cells. These anti-inflammatory effects were mediated through suppressing nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, we found that oxyresveratrol reduced reactive oxygen species (ROS) levels. To conclude, the current results demonstrated the protective role of oxyresveratrol against LPS-induced inflammation and oxidative stress in bEnd.3 cells, suggesting its potential effect for mitigating neurodegenerative and cerebrovascular diseases.
{"title":"Oxyresveratrol reduces lipopolysaccharide-induced inflammation and oxidative stress through inactivation of MAPK and NF-κB signaling in brain endothelial cells","authors":"","doi":"10.1016/j.bbrep.2024.101823","DOIUrl":"10.1016/j.bbrep.2024.101823","url":null,"abstract":"<div><p>Inflammatory responses and oxidative stress damage the integrity of the blood-brain barrier (BBB), which is a primary pathological modulator of neurodegenerative diseases. Brain endothelial cells are crucial components of BBB. In the present study, the effect of oxyresveratrol on lipopolysaccharide (LPS)-induced brain endothelial (bEnd.3) cells was assessed. Our results showed that oxyresveratrol diminished protein expressions of inducible nitric oxide synthase (iNOS) and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO) production, and proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) in LPS-elicited bEnd.3 cells. These anti-inflammatory effects were mediated through suppressing nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, we found that oxyresveratrol reduced reactive oxygen species (ROS) levels. To conclude, the current results demonstrated the protective role of oxyresveratrol against LPS-induced inflammation and oxidative stress in bEnd.3 cells, suggesting its potential effect for mitigating neurodegenerative and cerebrovascular diseases.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001870/pdfft?md5=4f36cbea5e641469209a5eaea1632a17&pid=1-s2.0-S2405580824001870-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150193","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}
Pub Date : 2024-09-06DOI: 10.1016/j.bbrep.2024.101815
Carotenoids are potential antioxidants offering extensive human health benefits including protection against chronic diseases. Augmenting the supply of health-benefiting compounds/metabolites through dietary supplements is the most sustainable way for a healthy life. Our study compares the traditional rice cultivar Kavuni and the white rice variety ASD 16. RNA-Seq analysis was carried out in the maturing panicles of Kavuni, which are enriched with antioxidants such as the therapeutic carotenoid lutein, polyphenols, and anthocyanins, along with “ASD 16”, a popularly eaten white rice variety, to elucidate the molecular networks regulating accumulation of health benefiting compounds. Systematic analysis of transcriptome data identified preferential up-regulation of carotenoid precursors (OsDXS, OsGGPS) and key carotenoid biosynthetic genes (OsPSY1, OsZ-ISO) in the maturing grains of Kavuni. Our study also identified enhanced expression of OsLYC-E, OsCYP97A, and OsCYP97C transcripts involved in the alpha-carotenoid biosynthetic pathway and thereby leading to elevated lutein content in the grains of Kavuni. Kavuni grains showed preferential down-regulation of negative regulators of carotenoid metabolism viz., AP2 and HY5 and preferential up-regulation of positive modulators of carotenoid metabolism viz., Orange, OsDjB7, and OsSET29, thus creating a favorable molecular framework for carotenoid accumulation. Our study has unearthed valuable gene control points for precise manipulation of carotenoid profiles through CRISPR-based gene editing in rice grains. Perturbation of carotenoid biosynthesis holds unprecedented potential for the rapid development of the next generation of ‘Golden rice’.
{"title":"Identifying molecular targets for modulating carotenoid accumulation in rice grains","authors":"","doi":"10.1016/j.bbrep.2024.101815","DOIUrl":"10.1016/j.bbrep.2024.101815","url":null,"abstract":"<div><p>Carotenoids are potential antioxidants offering extensive human health benefits including protection against chronic diseases. Augmenting the supply of health-benefiting compounds/metabolites through dietary supplements is the most sustainable way for a healthy life. Our study compares the traditional rice cultivar Kavuni and the white rice variety ASD 16. RNA-Seq analysis was carried out in the maturing panicles of Kavuni, which are enriched with antioxidants such as the therapeutic carotenoid lutein, polyphenols, and anthocyanins, along with “ASD 16”, a popularly eaten white rice variety, to elucidate the molecular networks regulating accumulation of health benefiting compounds. Systematic analysis of transcriptome data identified preferential up-regulation of carotenoid precursors (<em>OsDXS</em>, <em>OsGGPS</em>) and key carotenoid biosynthetic genes (<em>OsPSY1</em>, <em>OsZ-ISO</em>) in the maturing grains of Kavuni. Our study also identified enhanced expression of <em>OsLYC-E</em>, <em>OsCYP97A,</em> and <em>OsCYP97C</em> transcripts involved in the alpha-carotenoid biosynthetic pathway and thereby leading to elevated lutein content in the grains of Kavuni. Kavuni grains showed preferential down-regulation of negative regulators of carotenoid metabolism viz., AP2 and HY5 and preferential up-regulation of positive modulators of carotenoid metabolism viz., <em>Orange</em>, <em>OsDjB7,</em> and <em>OsSET29</em>, thus creating a favorable molecular framework for carotenoid accumulation. Our study has unearthed valuable gene control points for precise manipulation of carotenoid profiles through CRISPR-based gene editing in rice grains. Perturbation of carotenoid biosynthesis holds unprecedented potential for the rapid development of the next generation of ‘Golden rice’.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001791/pdfft?md5=9c44fab5940a2f799c998f97f4af1b36&pid=1-s2.0-S2405580824001791-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150195","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}
Pub Date : 2024-09-05DOI: 10.1016/j.bbrep.2024.101818
Recently, we have reported that biogenic silver/silver chloride nanoparticles from Asparagus racemosus (A. racemosus-AgCl-NPs) and Kaempferia rotunda (K. rotunda-Ag/AgCl-NPs) inhibited different cancer cells by inducing apoptosis and several genes alteration. Here for the first time, we assessed the effects of these two nanoparticles on human lung (A549) and hepatocellular (SMMC-7721) carcinoma cell lines. A. racemosus-AgCl-NPs and K. rotunda-Ag/AgCl-NPs inhibited A549 cell growth with IC50 values of 22.7 and 59.7 μg/ml and the calculated IC50 values for SMMC-7721 cell were 89.3 and 126.3 μg/ml, respectively. A. racemosus-AgCl-NPs exerted higher cytotoxicity against HEK293T cells than doxorubicin and K. rotunda-Ag/AgCl-NPs. Both the nanoparticles induced apoptosis in A549 and SMMC-7721 cell lines. A significant rise of early apoptotic cells and late apoptotic cells was found for A549 cells after treatment with A. racemosus-AgCl-NPs and stained with FITC-annexin V/PI. Apoptosis in A549 cells was further confirmed by monitoring the alteration of the expression level of several genes using real-time PCR and cell cycle arrest by flowcytometry after treatment with A. racemosus-AgCl-NPs. The expression of STAT-3, TNFα, and EGFR genes was decreased with the increase of caspase-8, FAS, and FADD gene expression. G2/M cell cycle phase was arrested after treatment of A549 cells with A. racemosus-AgCl-NPs.
{"title":"Asparagus racemosus silver chloride nanoparticles and Kaempferia rotunda mediated silver/silver chloride nanoparticles inhibit human hepatocellular and lung cancer cell lines","authors":"","doi":"10.1016/j.bbrep.2024.101818","DOIUrl":"10.1016/j.bbrep.2024.101818","url":null,"abstract":"<div><p>Recently, we have reported that biogenic silver/silver chloride nanoparticles from <em>Asparagus racemosus</em> (<em>A. racemosus</em>-AgCl-NPs) and <em>Kaempferia rotunda</em> (<em>K. rotunda</em>-Ag/AgCl-NPs) inhibited different cancer cells by inducing apoptosis and several genes alteration. Here for the first time, we assessed the effects of these two nanoparticles on human lung (A549) and hepatocellular (SMMC-7721) carcinoma cell lines. <em>A. racemosus-</em>AgCl-NPs and <em>K. rotunda</em>-Ag/AgCl-NPs inhibited A549 cell growth with IC<sub>50</sub> values of 22.7 and 59.7 μg/ml and the calculated IC<sub>50</sub> values for SMMC-7721 cell were 89.3 and 126.3 μg/ml, respectively. <em>A. racemosus</em>-AgCl-NPs exerted higher cytotoxicity against HEK293T cells than doxorubicin and <em>K. rotunda</em>-Ag/AgCl-NPs. Both the nanoparticles induced apoptosis in A549 and SMMC-7721 cell lines. A significant rise of early apoptotic cells and late apoptotic cells was found for A549 cells after treatment with <em>A. racemosus</em>-AgCl-NPs and stained with FITC-annexin V/PI. Apoptosis in A549 cells was further confirmed by monitoring the alteration of the expression level of several genes using real-time PCR and cell cycle arrest by flowcytometry after treatment with <em>A. racemosus</em>-AgCl-NPs. The expression of STAT-3, TNFα, and EGFR genes was decreased with the increase of caspase-8, FAS, and FADD gene expression. G<sub>2</sub>/M cell cycle phase was arrested after treatment of A549 cells with <em>A. racemosus</em>-AgCl-NPs.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001821/pdfft?md5=b85d7f30e299f375490840e9faab62f5&pid=1-s2.0-S2405580824001821-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150196","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}
Pub Date : 2024-09-05DOI: 10.1016/j.bbrep.2024.101822
Lysosome-associated membrane protein-2 (LAMP2) deficiency causes the human Danon disease and represents a lysosomal dysfunction because of its pivotal role in regulating autophagy and lysosome biogenesis. LAMP2-deficient mice exhibit a spectrum of phenotypes, including cardioskeletal myopathy, mental retardation, and retinopathy, similar to those observed in patients with Danon disease. Its pathology is thought to involve altered energy metabolism and lipid dysregulation; however, the lipidomic profiles of LAMP2-deficient animals have not been investigated. In this study, we investigated lipid alterations in LAMP2 KO mice tissues, including those of the liver, plasma, and retina, using liquid chromatography-mass spectrometry. Our results revealed significantly increased free fatty acid (FFA) levels and decreased in triglyceride (TG) levels in LAMP2 KO liver tissues at three and six months. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species significantly decreased in LAMP2 KO mice livers at six months. Similarly, plasma TG and PC/PE levels decreased in LAMP2 KO mice. In contrast, plasma FFA levels were significantly lower in LAMP2 KO mice. Retina FFA levels were elevated in LAMP2 KO mice, accompanied by a partial decrease in PC/PE at six months. In summary, FFA levels increased in several tissues but not in the LAMP2 KO mice plasma, suggesting the potential consumption of FFA as an energy source in the peripheral tissues. The depletion of TG and PC/PE accelerated with age, suggesting an underlying age-dependent energy crisis condition. Our findings underscore the dysregulated distribution of fatty acids in LAMP2-deficient animals and provide new mechanistic insights into the pathology of Danon disease.
溶酶体相关膜蛋白-2(LAMP2)缺乏症会导致人类达农病,由于它在调节自噬和溶酶体生物生成方面起着关键作用,因此是一种溶酶体功能障碍。LAMP2 缺陷小鼠表现出一系列表型,包括心肌肌病、智力迟钝和视网膜病变,与达农病患者的表现类似。其病理被认为涉及能量代谢的改变和脂质失调;然而,尚未对 LAMP2 基因缺陷动物的脂质组特征进行研究。在本研究中,我们使用液相色谱-质谱法研究了 LAMP2 KO 小鼠组织中的脂质变化,包括肝脏、血浆和视网膜组织。结果发现,LAMP2 KO小鼠肝脏组织中游离脂肪酸(FFA)水平在三个月和六个月后明显升高,甘油三酯(TG)水平则明显下降。六个月后,LAMP2 KO小鼠肝脏中磷脂酰胆碱(PC)和磷脂酰乙醇胺(PE)的种类明显减少。同样,LAMP2 KO 小鼠的血浆 TG 和 PC/PE 水平也有所下降。相反,LAMP2 KO 小鼠血浆中的 FFA 水平明显降低。LAMP2 KO 小鼠视网膜中的 FFA 水平升高,6 个月时 PC/PE 水平部分下降。总之,一些组织中的 FFA 水平升高,但 LAMP2 KO 小鼠血浆中的 FFA 水平并没有升高,这表明外周组织可能消耗 FFA 作为能量来源。随着年龄的增长,TG 和 PC/PE 的消耗速度加快,这表明存在潜在的年龄依赖性能量危机。我们的发现强调了脂肪酸在 LAMP2 缺乏动物体内的分布失调,并为达农病的病理机制提供了新的见解。
{"title":"Altered fatty acid distribution in lysosome-associated membrane protein-2 deficient mice","authors":"","doi":"10.1016/j.bbrep.2024.101822","DOIUrl":"10.1016/j.bbrep.2024.101822","url":null,"abstract":"<div><p>Lysosome-associated membrane protein-2 (LAMP2) deficiency causes the human Danon disease and represents a lysosomal dysfunction because of its pivotal role in regulating autophagy and lysosome biogenesis. LAMP2-deficient mice exhibit a spectrum of phenotypes, including cardioskeletal myopathy, mental retardation, and retinopathy, similar to those observed in patients with Danon disease. Its pathology is thought to involve altered energy metabolism and lipid dysregulation; however, the lipidomic profiles of LAMP2-deficient animals have not been investigated. In this study, we investigated lipid alterations in LAMP2 KO mice tissues, including those of the liver, plasma, and retina, using liquid chromatography-mass spectrometry. Our results revealed significantly increased free fatty acid (FFA) levels and decreased in triglyceride (TG) levels in LAMP2 KO liver tissues at three and six months. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species significantly decreased in LAMP2 KO mice livers at six months. Similarly, plasma TG and PC/PE levels decreased in LAMP2 KO mice. In contrast, plasma FFA levels were significantly lower in LAMP2 KO mice. Retina FFA levels were elevated in LAMP2 KO mice, accompanied by a partial decrease in PC/PE at six months. In summary, FFA levels increased in several tissues but not in the LAMP2 KO mice plasma, suggesting the potential consumption of FFA as an energy source in the peripheral tissues. The depletion of TG and PC/PE accelerated with age, suggesting an underlying age-dependent energy crisis condition. Our findings underscore the dysregulated distribution of fatty acids in LAMP2-deficient animals and provide new mechanistic insights into the pathology of Danon disease.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001869/pdfft?md5=b3a75aa82ec93056480dab7bade430a1&pid=1-s2.0-S2405580824001869-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150197","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}
Pub Date : 2024-09-04DOI: 10.1016/j.bbrep.2024.101821
Pseudomonas aeruginosa, a common cause of morbidity in cystic fibrosis, chronically infects the patient's lungs by forming an alginate-containing biofilm. Alginate lyases are polysaccharide lyases that lyse alginate and are, therefore, potential biofilm-disruptive agents. However, cystic fibrosis sputum contains high levels of metals such as iron and zinc. The efficacy of alginate lyases under these conditions of elevated metal concentrations has not been categorically determined. Here, we have assessed the enzyme activity of two exolytic and five endolytic alginate lyases in the presence of metal ions (Fe2+, Zn2+, Mn2+, Mg2+, Ca2+, Ni2+, Cu2+) elevated in the cystic fibrosis lung milieu. Several of these alginate lyases exhibited increased activity in the presence of Ca2+, and the polysaccharide lyase family 7 members studied here exhibited decreased activity in the presence of Zn2+. The enzyme activity of the PL7 alginate lyases from Cellulophaga algicola (CaAly/CaFLDAly) and Vibrio sp. (VspAlyVI) was not affected in the presence of a mix of all the above-mentioned metal ions at the elevated concentrations found in the cystic fibrosis lung milieu. Specific alginate lyases might, therefore, retain the ability to degrade the alginate-containing Pseudomonas biofilm in the presence of metal ions elevated in the cystic fibrosis lung milieu.
{"title":"A comparative study of the efficacy of alginate lyases in the presence of metal ions elevated in the cystic fibrosis lung milieu","authors":"","doi":"10.1016/j.bbrep.2024.101821","DOIUrl":"10.1016/j.bbrep.2024.101821","url":null,"abstract":"<div><p><em>Pseudomonas aeruginosa</em>, a common cause of morbidity in cystic fibrosis, chronically infects the patient's lungs by forming an alginate-containing biofilm. Alginate lyases are polysaccharide lyases that lyse alginate and are, therefore, potential biofilm-disruptive agents. However, cystic fibrosis sputum contains high levels of metals such as iron and zinc. The efficacy of alginate lyases under these conditions of elevated metal concentrations has not been categorically determined. Here, we have assessed the enzyme activity of two exolytic and five endolytic alginate lyases in the presence of metal ions (Fe<sup>2+</sup>, Zn<sup>2+</sup>, Mn<sup>2+</sup>, Mg<sup>2+</sup>, Ca<sup>2+</sup>, Ni<sup>2+</sup>, Cu<sup>2+</sup>) elevated in the cystic fibrosis lung milieu. Several of these alginate lyases exhibited increased activity in the presence of Ca<sup>2+</sup>, and the polysaccharide lyase family 7 members studied here exhibited decreased activity in the presence of Zn<sup>2+</sup>. The enzyme activity of the PL7 alginate lyases from <em>Cellulophaga algicola</em> (CaAly/CaFLDAly) and <em>Vibrio</em> sp. (VspAlyVI) was not affected in the presence of a mix of all the above-mentioned metal ions at the elevated concentrations found in the cystic fibrosis lung milieu. Specific alginate lyases might, therefore, retain the ability to degrade the alginate-containing <em>Pseudomonas</em> biofilm in the presence of metal ions elevated in the cystic fibrosis lung milieu.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001857/pdfft?md5=cb1e013e12072992449560db1623f653&pid=1-s2.0-S2405580824001857-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136217","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}