Journal of Biochemical and Molecular Toxicology最新文献_第4页

Mechanisms of METTL14-Mediated m6A Modification in Promoting Iron Overload-Induced Lipid Peroxidative Damage in Vascular Endothelial Cells to Aggravate Atherosclerosis METTL14 介导的 m6A 修饰促进铁超载诱导的血管内皮细胞脂质过氧化损伤加重动脉粥样硬化的机制

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-26 DOI: 10.1002/jbt.70066

Xiao-li Min, Si-xian Lin, Xiao-hong Zhao, Qing Zhao, Yun-fei Li, Xu-hui Li, Xiao-yong Liu, Yi Cao, Yu-long Sun, Yong Zeng

{"title":"Mechanisms of METTL14-Mediated m6A Modification in Promoting Iron Overload-Induced Lipid Peroxidative Damage in Vascular Endothelial Cells to Aggravate Atherosclerosis","authors":"Xiao-li Min, Si-xian Lin, Xiao-hong Zhao, Qing Zhao, Yun-fei Li, Xu-hui Li, Xiao-yong Liu, Yi Cao, Yu-long Sun, Yong Zeng","doi":"10.1002/jbt.70066","DOIUrl":"10.1002/jbt.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>Atherosclerosis (AS) is a chronic multifactorial disease with damage to vascular endothelial cells (VECs). This study sought to delve into the mechanism of methyltransferase-like 14 (METTL14) in iron overload-induced lipid peroxidative damage in AS. AS mouse model and cell model were established. Levels of METTL14/circRNA coded by the Arhgap12 (circARHGAP12)/Aspartate β-hydroxylase (ASPH) were determined. AS plaque area/lipid deposition/lipid metabolism in AS mice and iron overload in VECs were evaluated. N6-methyladenosine (m6A) level and METTL14 enrichment and human antigen R (HuR) in circARHGAP12 or ASPH were measured. The mRNA stability of circARHGAP12 or ASPH was analyzed. We observed that METTL14 was upregulated in AS mice. METTL14 downregulation reduced plaque area/lipid deposition/iron overload/peroxidative damage in AS mice. In cell models, METTL14 downregulation could VEC injury/iron overload/lipid peroxidative damage. Mechanically, METTL14 increased the stability and expression of circARHGAP12 through m6A modification, further stabilized ASPH mRNA, and promoted ASPH transcription by binding to HuR. Overexpression of circARHGAP12 or inhibition of ASPH averted the protective role of METTL14 downregulation against iron overload-induced peroxidative damage in AS. In conclusion, METTL14-mediated m6A modification upregulated circARHGAP12 and ASPH to aggravate overload-induced lipid peroxidative damage and facilitate AS progression.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dabrafenib Inhibits Egr-1-Mediated Adhesion of Thyroid Cancer Cells to Pulmonary Microvascular Endothelium 达拉菲尼抑制 Egr-1 介导的甲状腺癌细胞与肺微血管内皮的粘附

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-26 DOI: 10.1002/jbt.70060

Yanchao Qin, Wei Ding, Xuesong Wu, Dongguang Qin

{"title":"Dabrafenib Inhibits Egr-1-Mediated Adhesion of Thyroid Cancer Cells to Pulmonary Microvascular Endothelium","authors":"Yanchao Qin, Wei Ding, Xuesong Wu, Dongguang Qin","doi":"10.1002/jbt.70060","DOIUrl":"10.1002/jbt.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Cell-cell adhesion between thyroid tumor cells and pulmonary endothelial cells plays a critical role in the development of lung metastases from primary thyroid cancer. Dabrafenib, a selective inhibitor for B-RAF kinase, has been approved for cancer treatment. However, its effects on pulmonary metastases originating from primary thyroid cancer remain unclear. In this study, we demonstrate that conditioned medium (CM) from the thyroid cancer SW579 cell line significantly elevated the expression of pro-inflammatory cytokines HMGB-1, IL-1β, and MCP-1 in human pulmonary microvascular endothelial cells (HPMECs), which was notably reduced by Dabrafenib. Additionally, exposure to the thyroid cancer SW579 CM increased the expression of endothelial adhesion molecules VCAM-1 and ICAM-1, as well as the adhesion of thyroid cancer SW579 cells to HPMECs, both of which were prevented by Dabrafenib. We also found that Dabrafenib mitigated oxidative stress induced by SW579 CM, as evidenced by increased glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels. Further investigation revealed that Dabrafenib's beneficial effects were mediated through the inhibition of Egr-1, and overexpression of Egr-1 reversed Dabrafenib's protective effect on the adhesion of thyroid cancer cells to HPMECs. Based on these results, we propose that Dabrafenib may have the potential to prevent pulmonary metastases of thyroid cancer cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Double-Negative T Cells Promote Liver Fibrosis Progression by Regulating Treg/Th17 双阴性 T 细胞通过调节 Treg/Th17 促进肝纤维化进展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-22 DOI: 10.1002/jbt.70028

Chenyang Han, Xiaoying Qian, Hongyan Pei, Caiqun Zhang, Jin Wang, Xiaohong Zhou, Wenyan Li, Yi Yang, Shasha Wu

{"title":"Double-Negative T Cells Promote Liver Fibrosis Progression by Regulating Treg/Th17","authors":"Chenyang Han, Xiaoying Qian, Hongyan Pei, Caiqun Zhang, Jin Wang, Xiaohong Zhou, Wenyan Li, Yi Yang, Shasha Wu","doi":"10.1002/jbt.70028","DOIUrl":"10.1002/jbt.70028","url":null,"abstract":"<p>We investigated the mechanism whereby double-negative T cells (DNTs) regulate Treg/Th17 balance to promote the progression of liver fibrosis. Liver fibrosis was induced with carbon tetrachloride (CCl4) in mice. Mouse DNTs were isolated, amplified and injected. The proportions of iTreg (CDF4+CD25+Foxp3+) and Th17 (CD4+IL-17A+) in peripheral mononuclear cells, spleen and liver were analyzed by flow cytometry, and the cytokine levels were determined through enzyme-linked immunosorbent assay (ELISA). DNTs could promote the Th17 differentiation and inhibit the iTreg differentiation. The role of DNTs in promoting liver fibrosis progression and tissue inflammation was exerted through activation of IκBa. The use of IL-17A monoclonal antibody enabled suppression of the DNTs effects, reduction of the Th17 proportion and alleviation of liver fibrosis. Hal could suppress the Th17 differentiation and the effect of DNTs. DNTs can promote the Th17 differentiation through IL-17A and inhibit iTreg differentiation, thereby facilitating the liver fibrosis progression and microenvironmental inflammation. DNTs are a kind of important immunocytes that promote the liver fibrosis progression.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PKN2 Promotes Peripheral Nerve Repair by Regulating Autophagy via Activation of the AKT-mTOR Pathway: An In Vitro Study PKN2 通过激活 AKT-mTOR 通路调节自噬促进外周神经修复：体外研究。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-22 DOI: 10.1002/jbt.70063

Lin Wang, Yuan-sheng Huang

引用次数: 0

Mincle Maintains M1 Polarization of Macrophages and Contributes to Renal Aging Through the Syk/NF-κB Pathway Mincle通过Syk/NF-κB途径维持巨噬细胞的M1极化并促进肾脏衰老

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-22 DOI: 10.1002/jbt.70062

Lingshuang Sun, Hua Liu, Kehui Shi, Meng Wei, Hongli Jiang

{"title":"Mincle Maintains M1 Polarization of Macrophages and Contributes to Renal Aging Through the Syk/NF-κB Pathway","authors":"Lingshuang Sun, Hua Liu, Kehui Shi, Meng Wei, Hongli Jiang","doi":"10.1002/jbt.70062","DOIUrl":"10.1002/jbt.70062","url":null,"abstract":"<div>\u0000 \u0000 <p>Kidney is a classic organ undergoing senescence, and chronic inflammation has an important effect in cellular senescence. Mincle has been shown to be vital for maintaining the M1 phenotype of macrophages, but its role in regulating renal aging has yet to be explored. Young (2 months of age) and old (24 months of age) mice were used to analyze the changes of kidney damage during natural aging. Mice were subcutaneously injected with D-galactose (D-gal) to establish a renal aging model, and miR-6948-3p mimic and Mincle siRNA were administered via the tail vein every 3 days. Aged kidney and experimental aging kidney were characterized by decreased renal function and structural damage, and upregulated expression of senescence-related proteins and SPAP components. The ratio of M1 macrophages was increased in the aged kidney, and Mincle accumulated in the aged kidney macrophages. Administration of miR-6948-3p mimic or Mincle siRNA alleviated D-gal-induced renal senescence. LPS was used to induce M1 polarization of bone marrow-derived macrophages, and a coculture system of M1 macrophages and mouse renal tubular epithelial cells (TCMK-1) was established. Mincle was upregulated in LPS-induced M1 macrophages in vitro, and silencing Mincle in M1 macrophages attenuated M1 macrophage-induced TCMK-1 cell senescence. Mechanistically, Mincle was regulated by miR-6948-3p and maintained the M1 phenotype of macrophages through the Syk/NF-κB pathway. In conclusion, Mincle, posttranscriptionally suppressed by miR-6948-3p, modulated renal senescence by maintaining the phenotype of M1 macrophages through the Syk/NF-κB pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular Vesicles Derived Ectonucleoside Triphosphate Diphosphohydrolase 3 Alleviates Mitochondrial Dysfunction of Osteoarthritis Chondrocytes via Ectonucleotide Pyrophosphatase/Phosphodiesterase 1-Induced Suppression of the AKT/Notch2 Pathway 细胞外囊泡衍生的三磷酸异核苷二磷酸水解酶3通过异核苷酸焦磷酸酶/磷酸二酯酶1诱导的AKT/Notch2通路抑制作用缓解骨关节炎软骨细胞的线粒体功能障碍

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-21 DOI: 10.1002/jbt.70064

Xin Tang, Jingsheng He, Ye Hao

{"title":"Extracellular Vesicles Derived Ectonucleoside Triphosphate Diphosphohydrolase 3 Alleviates Mitochondrial Dysfunction of Osteoarthritis Chondrocytes via Ectonucleotide Pyrophosphatase/Phosphodiesterase 1-Induced Suppression of the AKT/Notch2 Pathway","authors":"Xin Tang, Jingsheng He, Ye Hao","doi":"10.1002/jbt.70064","DOIUrl":"10.1002/jbt.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoarthritis (OA) is the most common joint disease that usually starts from joint cartilage injury. Notch2, a versatile signaling in human development and diseases, was recently uncovered to be an important regulator in chondrocyte damage. However, in OA chondrocytes, how Notch2 activation is dysregulated is largely unknown. Here, integrated bioinformatic analysis was performed on GEO datasets (GSE199193 and GSE224255) to search potential extracellular vesicles (EVs) derived regulators of Notch2 in OA chondrocytes. Ectonucleoside triphosphate diphosphohydrolase 3 (Entpd3), a most differentially expressed gene both in LPS-induced macrophage EV and Notch2 mutant chondrocytes, was screened as the candidate regulator of Notch2 in OA chondrocytes. Gain-of-function experiments in cultured human chondrocytes revealed that recombinant Entpd3 protein and macrophage EV both had a protective effect on LPS-induced inflammation, oxidative stress, apoptosis, and collagen loss in chondrocytes. In terms of mechanism, Entpd3 directly interacted with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and suppressed AKT/Notch2-mediated mitochondrial dysfunction. Finally, we verified that either macrophage EV administration or Entpd3 overexpression was able to alleviate osteoarthritis in mice in vivo. In conclusion, Entpd3 is identified as a new regulator in OA, which alleviates mitochondrial dysfunction induced chondrocyte damage via ENPP1-induced suppression of the AKT/Notch2 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic Interaction Between F-Box Encoding UCC1 and RRM3 Regulates Growth Rate, Cell Size, and Stress Tolerance in Saccharomyces cerevisiae F-Box 编码 UCC1 与 RRM3 之间的遗传相互作用可调控酿酒酵母的生长速度、细胞大小和应激耐受性。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-19 DOI: 10.1002/jbt.70059

Monika Pandita, Heena Shoket, Rakesh Kumar, Narendra K. Bairwa

{"title":"Genetic Interaction Between F-Box Encoding UCC1 and RRM3 Regulates Growth Rate, Cell Size, and Stress Tolerance in Saccharomyces cerevisiae","authors":"Monika Pandita, Heena Shoket, Rakesh Kumar, Narendra K. Bairwa","doi":"10.1002/jbt.70059","DOIUrl":"10.1002/jbt.70059","url":null,"abstract":"<div>\u0000 \u0000 <p>Ucc1, an F-box motif-containing protein of <i>Saccharomyces cerevisiae</i> encoded by <i>UCC1</i> regulates energy metabolism through proteasomal degradation of citrate synthase Cit2 and inactivation of the glyoxylate cycle when glucose is present as the main carbon source in the growth medium. Rrm3, a Pif1 family DNA helicase, encoded by <i>RRM3</i> regulates the movement of the replication forks during the DNA replication process. Here in this study, we present evidence of binary genetic interaction between both the genes, <i>UCC1</i> and <i>RRM3</i>, that determine the growth rate, cell morphology, cell size, apoptosis, and stress response. The absence of both genes <i>UCC1</i> and <i>RRM3</i> leads to altered cell morphology, increased growth rate, utilization of alternate carbon sources, resistance to hydrogen peroxide, and susceptibility to acetic acid-induced apoptosis. Further, the genetic interaction network analysis shows both the genes <i>UCC1</i> and <i>RRM3</i> interaction through the <i>SGS1</i> and cross-link among metabolic, glyoxylate, DNA replication, and retrograde signaling pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plausible Action of N-(3,4-Dimethoxy-Phenyl)-6,7-Dimethoxyquinazoline-4-Amine (TKM01) as an Armor Against Alzheimer's Disease: In Silico and In Vivo Insights N-(3,4-二甲氧基苯基)-6,7-二甲氧基喹唑啉-4-胺（TKM01）作为阿尔茨海默病防护剂的合理作用：硅学和体内观察。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70048

Mohd Kashif, Karthikeyan Chandrabose, Ashok Kumar Pandurangan

{"title":"Plausible Action of N-(3,4-Dimethoxy-Phenyl)-6,7-Dimethoxyquinazoline-4-Amine (TKM01) as an Armor Against Alzheimer's Disease: In Silico and In Vivo Insights","authors":"Mohd Kashif, Karthikeyan Chandrabose, Ashok Kumar Pandurangan","doi":"10.1002/jbt.70048","DOIUrl":"10.1002/jbt.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) affects millions of people and has limited treatment options, thus making it a global health concern. Amyloid β (Aβ), a disrupted cholinergic system with high acetylcholinesterase (AChE), oxidative stress (OS), reduced antioxidants, and neuroinflammation are key factors influencing AD progression. Prior research has shown that AChE can interact with Aβ and increase its accumulation and neurotoxicity, so targeting AChEs and Aβ could be a potential therapeutic approach for AD treatment. It has been known that nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit Aβ accumulation. Previously, TKM01, a derivative of 4-anilinoquinazoline, has demonstrated inhibitory effects against GSK-3β—a regulator in AD progression. The current research included molecular docking studies of NSAIDs and TKM01 with Aβ and AChEs as targets. TKM01 exhibited a higher binding affinity with Aβ among all tested compounds. Molecular dynamic (MD) simulations confirmed the stability of the protein-TKM01 complexes. TKM01 also exhibited favorable drug-likeness properties, and no hepatoxicity was visualized in comparison with other compounds. Further, in vitro assay showed an inhibitory action of TKM01 (50–1200 µg/mL) on AChEs. In the in vivo studies on zebrafish larvae brains, we found that TKM01 (120 and 240 µg/mL) reduced the levels of AChEs and lipid peroxidation (LPO) and increased antioxidant superoxide dismutase (SOD) and catalase (CAT) in AlCl<sub>3</sub>(80 µM)-induced AD-like model. Additionally, TKM01 treatment was found to decrease pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. The current study demonstrates that TKM01 can be used to treat AD. Nonetheless, experimental validation is needed to reveal the cellular, sub-cellular, and molecular mechanisms and possible implications at a clinical stage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astaxanthin-S-Allyl Cysteine Ester Protects Pancreatic β-Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation 虾青素-S-烯丙基半胱氨酸酯通过抑制氧化应激、内质网应激和 mTOR 通路失调保护胰腺 β 细胞免受糖脂毒性影响

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70058

Penislusshiyan Sakayanathan, Chitra Loganathan, Palvannan Thayumanavan

{"title":"Astaxanthin-S-Allyl Cysteine Ester Protects Pancreatic β-Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation","authors":"Penislusshiyan Sakayanathan, Chitra Loganathan, Palvannan Thayumanavan","doi":"10.1002/jbt.70058","DOIUrl":"10.1002/jbt.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Glucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT-induced deleterious effect on β-cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin-s-allyl cysteine (AST-SAC) diester was studied against GLT in β-cells. <i>Mus musculus</i> pancreatic β-cell line (βTC-tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST-SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β-cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST-SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β-cells. AST-SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST-SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress-mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST-SAC. Due to these protective effects of AST-SAC the insulin secretion was well-maintained in β-cells under HG + PA exposure conditions. AST-SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER-stress mediated UPR pathway has promoted the β-cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β-cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paeonol Alleviates Subarachnoid Hemorrhage Injury in Rats Through Upregulation of SIRT1 and Inhibition of HMGB1/TLR4/MyD88/NF-κB Pathway 芍药酚通过上调 SIRT1 和抑制 HMGB1/TLR4/MyD88/NF-κB 通路缓解大鼠蛛网膜下腔出血损伤

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70035

Zhao Liu, Jun Zhu, Enyu Pan, Lujun Pang, Xiwei Zhou, Yanjun Che

{"title":"Paeonol Alleviates Subarachnoid Hemorrhage Injury in Rats Through Upregulation of SIRT1 and Inhibition of HMGB1/TLR4/MyD88/NF-κB Pathway","authors":"Zhao Liu, Jun Zhu, Enyu Pan, Lujun Pang, Xiwei Zhou, Yanjun Che","doi":"10.1002/jbt.70035","DOIUrl":"10.1002/jbt.70035","url":null,"abstract":"<div>\u0000 \u0000 <p>Paeonol is a principle bioactive compound separated from the root bark of Cortex Moutan and has been shown to confer various biological functions, including antineuroinflammation and neuroprotection. Inflammation, blood–brain barrier (BBB), permeability, and apoptosis are three major underlying mechanisms involved in early brain injury (EBI) postsubarachnoid hemorrhage (SAH). This study aimed to detect the roles and mechanisms of paeonol in EBI following SAH. A SAH model was established by an endovascular perforation method in Sprague-Dawley rats. The localizations of HMGB1 and p65 were identified by immunofluorescence staining. Protein levels were measured by western blot analysis. The serum levels of HMGB1 and the levels of inflammatory cytokines in the brain cortex were evaluated by ELISA. Hematoxylin and eosin staining was conducted to detect neuronal degeneration. Brain water content and Evans blue extravasation were assessed to determine EBI. Neuronal apoptosis was examined by TUNEL. Paeonol deacetylated HMGB1 by upregulating SIRT1 level. SIRT1 inhibition attenuated the protective effects of paeonol against neurological dysfunctions, brain edema, and BBB disruption. SIRT1 inhibition rescued the paeonol-induced inhibition in inflammatory response. The paeonol-induced decrease in neuronal apoptosis was restored by SIRT1 inhibitor. The paeonol-mediated deactivated TLR4/MyD88/NF-κB pathway was activated by SIRT1 inhibitor. Paeonol alleviates the SAH injury in rats by upregulating SIRT1 to inactivate the HMGB1/TLR4/MyD88/NF-κB pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0