Nitric oxide : biology and chemistry最新文献

{"title":"Synthesis, structure, spectra, cytotoxicity and photo induced NO release of four isomeric nitrosylruthenium complexes","authors":"Jia Shi ,&nbsp;Yuhua Liu ,&nbsp;Shuxiang Jiao ,&nbsp;Tao Wu ,&nbsp;Ai Wang ,&nbsp;Wenming Wang ,&nbsp;Leilei Xie ,&nbsp;Yanhong Liu ,&nbsp;Hongfei Wang","doi":"10.1016/j.niox.2024.09.007","DOIUrl":"10.1016/j.niox.2024.09.007","url":null,"abstract":"<div><div>Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (<strong>1</strong>–<strong>4</strong>) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, <span>l</span>-valine) and characterized by ¹H NMR, ¹³C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes <strong>1</strong>–<strong>4</strong> inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 58-68"},"PeriodicalIF":3.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide in the cardio-cerebrovascular system: Source, regulation and application","authors":"Xiaoming Fu ,&nbsp;Haowei Lu ,&nbsp;Meng Gao ,&nbsp;Pinghe Li ,&nbsp;Yan He ,&nbsp;Yu He ,&nbsp;Xiaojian Luo ,&nbsp;Xiaoyong Rao ,&nbsp;Wei Liu","doi":"10.1016/j.niox.2024.09.005","DOIUrl":"10.1016/j.niox.2024.09.005","url":null,"abstract":"<div><div>Nitric oxide (NO) plays a crucial role as a messenger or effector in the body, yet it presents a dual impact on cardio-cerebrovascular health. Under normal physiological conditions, NO exhibits vasodilatory effects, regulates blood pressure, inhibits platelet aggregation, and offers neuroprotective actions. However, in pathological situations, excessive NO production contributes to or worsens inflammation within the body. Moreover, NO may combine with reactive oxygen species (ROS), generating harmful substances that intensify physical harm. This paper succinctly reviews pertinent literature to clarify the in vivo and in vitro origins of NO, its regulatory function in the cardio-cerebrovascular system, and the advantages and disadvantages associated with NO donor drugs, NO delivery systems, and vascular stent materials for treating cardio-cerebrovascular disease. The findings provide a theoretical foundation for the application of NO in cardio-cerebrovascular diseases.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 48-57"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen sulfide upregulates SIRT1 to inhibit ox-HDL-induced endothelial cell damage and mitochondrial dysfunction","authors":"Yuanqin Zhao ,&nbsp;Yanxia Wang ,&nbsp;Hongyu Zheng ,&nbsp;Qian Xu ,&nbsp;Kun Zhou ,&nbsp;Huiting Liu ,&nbsp;Yu Xia ,&nbsp;Dang-Heng Wei ,&nbsp;Miao Jiang ,&nbsp;Zhi-Han Tang ,&nbsp;Lu-Shan Liu ,&nbsp;He Zheng ,&nbsp;Zhisheng Jiang","doi":"10.1016/j.niox.2024.09.006","DOIUrl":"10.1016/j.niox.2024.09.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Under normal circumstances, high-density lipoprotein (HDL) is considered to have cardiovascular protective effects, but the impact of oxidized HDL (ox-HDL) on vascular endothelial function remains poorly understood. Mitochondrial function is closely related to endothelial function, and hydrogen sulfide (H₂S) is a gas with endothelial protective properties. The novel hydrogen sulfide donor AP39 can target mitochondria to release H₂S, but the combined effects of ox-HDL and AP39 on vascular endothelium are not well studied.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We established a cell model of ox-HDL-induced endothelial cell damage and mitochondrial dysfunction using human umbilical vein endothelial cells (HUVECs) and conducted AP39 pretreatment. The experiments confirmed the functional damage and mitochondrial dysfunction in HUVECs caused by ox-HDL. Additionally, to further explore the role of SIRT1 in AS, we analyzed SIRT1 expression in AS carotid artery tissue. This included the analysis of differentially expressed genes from AS-related datasets, presented through volcano plots and heatmaps, with enrichment analysis of downregulated genes in KEGG pathways and GO functions. Furthermore, we evaluated the differences in SIRT1 expression in coronary arteries with varying degrees of stenosis and in early and late-stage AS carotid artery tissues, and analyzed data from SIRT1 knockout mouse models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The experimental results indicate that AP39 effectively alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. MTT and CCK-8 assays showed that ox-HDL treatment led to decreased cell viability and proliferation in HUVECs, reduced eNOS expression, and significantly increased levels of ICAM-1, IL-6, and TNF-α, along with enhanced monocyte adhesion. These findings reveal the damaging effects of ox-HDL on HUVECs. Transcriptomic data indicated that while SIRT1 expression did not significantly differ in coronary arteries with varying degrees of stenosis, it was notably downregulated in AS carotid artery tissues, especially in late-stage AS tissues. KEGG pathway enrichment analysis revealed that SIRT1 downregulated genes were associated with processes such as vascular smooth muscle contraction, while GO analysis showed that these downregulated genes were involved in muscle system processes and muscle contraction functions, further confirming SIRT1's critical role in AS pathology. In transcriptomic data from the SIRT1 knockout mouse model, elevated levels of inflammation-related proteins IL-6 and TNF-α were observed after SIRT1 knockout, along with decreased expression of the chaperone protein PGC-1α. The expression of mitochondrial-related functional proteins Nrf2 and PGC-1α was positively correlated with SIRT1 expression, while inflammation-related proteins ICAM-1, IL-6, IL-20, and TNF-α were negatively correlated with SIRT1 expression. We furth","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 78-89"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hunt for transnitrosylase","authors":"Surupa Chakraborty,&nbsp;Ankita Choudhuri ,&nbsp;Akansha Mishra ,&nbsp;Rajib Sengupta","doi":"10.1016/j.niox.2024.09.004","DOIUrl":"10.1016/j.niox.2024.09.004","url":null,"abstract":"<div><div>The biochemical interplay between antioxidants and pro-oxidants maintains the redox homeostatic balance of the cell, which, when perturbed to moderate or high extents, has been implicated in the onset and/or progression of chronic diseases such as diabetes mellitus, cancer, and neurodegenerative diseases. Thioredoxin, glutaredoxin, and lipoic acid-like thiol oxidoreductase systems constitute a unique ensemble of robust cellular antioxidant defenses, owing to their indispensable roles as S-denitrosylases, S-deglutathionylases, and disulfide reductants in maintaining a reduced free thiol state with biological relevance. Thus, in cells subjected to nitrosative stress, cellular antioxidants will S-denitrosylate their cognate S-nitrosoprotein substrates, rather than participate in <em>trans</em>-S-nitrosylation <em>via</em> protein-protein interactions. Researchers have been at the forefront of vaguely establishing the concept of ‘transnitrosylation’ and its influence on pathophysiology with experimental evidence from <em>in vitro</em> studies that lack proper biochemical logic. The suggestive and reiterative use of antioxidants as transnitrosylases in the scientific literature leaves us on a cliffhanger with several open-ended questions that prompted us to ‘hunt’ for scientific logic behind the <em>trans</em>-S-nitrosylation chemistry. Given the gravity of the situation and to look at the bigger picture of ‘<em>trans</em>-S-nitrosylation’, we aim to present a novel attempt at justifying the hesitance in accepting antioxidants as capable of transnitrosylating their cognate protein partners and reflecting on the need to resolve the controversy that would be crucial from the perspective of understanding therapeutic outcomes involving such cellular antioxidants in disease pathogenesis. Further characterization is required to identify the regulatory mechanisms or conditions where an antioxidant like Trx, Grx, or DJ-1 can act as a cellular transnitrosylase.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 31-47"},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of hydrogen sulfide-microRNA crosstalk in health and disease","authors":"Mi-Rong Jing ,&nbsp;Xiao-Yi Liang ,&nbsp;Yan-Xia Zhang ,&nbsp;Yi-Wen Zhu ,&nbsp;Yan Wang ,&nbsp;Ti Chu ,&nbsp;Yu-Qing Jin ,&nbsp;Chuan-Hao Zhang ,&nbsp;Shuai-Gang Zhu ,&nbsp;Chao-Jing Zhang ,&nbsp;Qi-Meng Wang ,&nbsp;Zhi-Fen Feng ,&nbsp;Xin-Ying Ji ,&nbsp;Dong-Dong Wu","doi":"10.1016/j.niox.2024.09.002","DOIUrl":"10.1016/j.niox.2024.09.002","url":null,"abstract":"<div><div>The mutual regulation between hydrogen sulfide (H₂S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H₂S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H₂S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H₂S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H₂S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H₂S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H₂S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 19-30"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H2S alleviated sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway","authors":"Chengqing Song ,&nbsp;Qian Chen ,&nbsp;Jiao Xu ,&nbsp;Kaichuan He ,&nbsp;Qi Guo ,&nbsp;Xu Teng ,&nbsp;Hongmei Xue ,&nbsp;Lin Xiao ,&nbsp;Danyang Tian ,&nbsp;Sheng Jin ,&nbsp;Cuixia An ,&nbsp;Yuming Wu","doi":"10.1016/j.niox.2024.09.003","DOIUrl":"10.1016/j.niox.2024.09.003","url":null,"abstract":"<div><p>To investigate the protective mechanisms of hydrogen sulfide (H₂S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H₂S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H₂S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with <span>dl</span>-propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H₂S influences the pathogenesis of SAKI, while exogenous H₂S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 11-18"},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in increasing efficiency of hydrogen sulfide in therapeutics: Strategies for targeted delivery as prodrugs","authors":"Tejasvi Pandey ,&nbsp;Vivek Pandey","doi":"10.1016/j.niox.2024.09.001","DOIUrl":"10.1016/j.niox.2024.09.001","url":null,"abstract":"<div><p>Hydrogen sulfide (H2S) has emerged as a potent therapeutic agent with diverse physiological functions, including vasodilation, anti-inflammation, and cytoprotection. However, its clinical application is limited due to its volatility and potential toxicity at high concentrations. To address these challenges, researchers have developed various H2S prodrugs that release H2S in a controlled and targeted manner. The review underscores the importance of targeting and delivery strategies in maximizing the therapeutic potential of H2S, a gasotransmitter with diverse physiological functions and therapeutic effects. By summarizing recent advancements, the review provides valuable insights for researchers and clinicians interested in harnessing the therapeutic benefits of H2S while minimizing off-target effects and toxicity. The integration of novel targeting and delivery approaches not only enhances the efficacy of H2S-based therapeutics but also expands the scope of potential applications, offering promising avenues for the development of new treatments for a variety of diseases and disorders.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"152 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of nitroglycerin treatment on cerebral ischaemia: A systematic review and meta-analysis of animal studies","authors":"Magdalena Litman ,&nbsp;Neil J. Spratt ,&nbsp;Daniel J. Beard","doi":"10.1016/j.niox.2024.08.003","DOIUrl":"10.1016/j.niox.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><p>Nitroglycerin has been of considerable interest as a treatment for ischaemic stroke. Recent clinical trials with nitroglycerin transdermal patches during the acute phase of stroke failed to improve functional outcomes. Systematic review and meta-analysis of the effectiveness of nitroglycerin in preclinical models of ischaemic stroke has not previously been reported, despite several clinical trials.</p></div><div><h3>Objective</h3><p>To conduct a systematic review and meta-analysis of preclinical evidence regarding the effect of nitroglycerin on infarct volume in animal models of ischaemic stroke.</p></div><div><h3>Summary of review</h3><p>The protocol was registered in PROSPERO (CRD42023432644). Our search identified 238 publications. Three publications met inclusion criteria (including 10 comparisons of infarct size). Study quality was modest (median 6 out of 9), with no evidence of publication bias. Nitroglycerin did not significantly reduce infarct volume (NMD point estimate 20.2 % reduction, 95 % CI −1.52–52.7 %, <em>p</em> = 0.068). Subgroup analysis suggested greater efficacy of nitroglycerin with direct intracarotid administration to the ischaemic territory at the time of reperfusion.</p></div><div><h3>Conclusions</h3><p>A small number of studies (three) were included in this review. Overall, nitroglycerin did not reduce infarct volume in experimental stroke models. However, nitroglycerin may be of benefit when administered directly into the ischaemic territory. Given nitroglycerin's short half-life, we propose this route may minimise harmful reduction of cerebral perfusion pressure resulting from hypotension following systemic administration.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"151 ","pages":"Pages 10-16"},"PeriodicalIF":3.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324001046/pdfft?md5=91e5cfa784368db27ad66c40f95a18f4&pid=1-s2.0-S1089860324001046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NO- and H2S- releasing nanomaterials: A crosstalk signaling pathway in cancer","authors":"Roberta Albino dos Reis ,&nbsp;Ishani Sarkar ,&nbsp;Maiara Gonçalves Rodrigues ,&nbsp;John B. Matson ,&nbsp;Amedea Barozzi Seabra ,&nbsp;Khosrow Kashfi","doi":"10.1016/j.niox.2024.08.002","DOIUrl":"10.1016/j.niox.2024.08.002","url":null,"abstract":"<div><p>The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H₂S) play important roles not only in maintaining physiological functions, but also in pathological conditions and events. Importantly, these molecules show a complex interplay in cancer biology, demonstrating both tumor-promoting and anti-tumor activities depending on their concentration, flux, and the environmental redox state. Additionally, various cell types respond differently to NO and H₂S. These gasotransmitters can be synergistically combined with traditional anticancer treatments such as radiotherapy, immunotherapy, chemotherapy, and phototherapy. Notably, NO, and more recently H₂S, have been shown to reverse multidrug resistance. Nanomaterials to deliver NO donors and, to a lesser extent, H₂S donors, have emerged as a promising approach for targeted delivery of these gasotransmitters. Nanotechnology has advanced the delivery of anticancer drugs, enhancing efficiency and reducing side effects on non-cancerous cells. This review highlights recent progress in the design of NO and H₂S-releasing nanomaterials for anticancer effects. It also explores the interactions between NO and H₂S, which are crucial for developing combined therapies and nanomedicines with minimal side effects.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"151 ","pages":"Pages 17-30"},"PeriodicalIF":3.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystathionine gamma-lyase deficiency exaggerates diethylnitrosamine-induced liver damage in mice","authors":"Samantha Ligi ,&nbsp;Arm Ali ,&nbsp;Guangdong Yang","doi":"10.1016/j.niox.2024.08.001","DOIUrl":"10.1016/j.niox.2024.08.001","url":null,"abstract":"<div><p>Cystathionine gamma-lyase (CSE) is a key enzyme in reverse transsulfuration pathway and contributes to the majority of H₂S generation in liver tissues via cysteine metabolism. Dysfunction of the CSE/H₂S system is linked to both chronic and acute liver damage. This study investigated the regulatory role of CSE deficiency on diethylnitrosamine (DEN)-induced liver damage in mice. A single injection of DEN was administered into 4-week-old male CSE knockout (CSE-KO) mice and wild-type (WT) littermates, and the mice were sacrificed at 28 weeks of age. Compared to age-matched WT mice, CSE-KO mice spontaneously developed steatosis with increased oxidative stress and higher expressions of inflammation and fibrosis-related genes at 28-weeks of age. Following DEN injection, CSE-KO mice experienced more severe liver damage in comparison with the WT group as reflected by elevated levels of lipid accumulation, increased activities of alanine aminotransferase and aspartate aminotransferase, higher oxidative stress and fibrosis development, and increased expressions of inflammation and fibrosis-related genes. No visible tumors were observed in both types of mice with DEN treatment. In addition, the expression levels of the three H₂S-generating proteins (CSE, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase) and the H₂S production rate in liver tissues were unaffected by DEN. Taken together, our study demonstrates that CSE provides a significant hepatoprotective effect and deficiency of CSE exaggerates DEN-induced liver damage in mice. Based on these findings, it can be suggested that targeting the CSE/H₂S signaling pathway could be a potential therapeutic target for the treatment of liver diseases.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"151 ","pages":"Pages 1-9"},"PeriodicalIF":3.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}