Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Tirzepatide Induces Ferroptosis in Glioblastoma Cell Lines via the SOX2/SLC7A11 Axis: A Potential Therapeutic Strategy for Glioma Treatment","authors":"Jiangtao Wang,&nbsp;Hang Chen,&nbsp;Xinjun Wang","doi":"10.1002/jbt.70392","DOIUrl":"https://doi.org/10.1002/jbt.70392","url":null,"abstract":"<div>\u0000 \u0000 <p>Tirzepatide, a dual agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors used in type 2 diabetes and obesity management, was investigated for its effects on glioma cells, focusing on its potential to induce ferroptosis. Tirzepatide treatment significantly inhibited glioma cell proliferation and migration, as demonstrated by the CCK-8 and Transwell migration assays. Tirzepatide also induced lipid peroxidation, evidenced by increased ROS levels, elevated MDA production, and reduced SOD activity, while the GSH/GSSG ratio was decreased, reflecting oxidative stress. Ferroptosis was further confirmed by increased Fe²⁺ concentrations and alterations in iron metabolism-related genes (Ferritin and TFR1) and lipid metabolism-related genes (ACSL4 and GPX4). Tirzepatide also inhibited the SOX2/SLC7A11 axis, which plays a critical role in resisting ferroptosis. Fer-1, a ferroptosis inhibitor, or SOX2 overexpression, markedly reduced Tirzepatide's effects on proliferation, migration, lipid peroxidation, and ferroptosis, highlighting the critical role of the SOX2/SLC7A11 axis in mediating these effects. These findings indicate that Tirzepatide inhibits glioma cell growth by inducing ferroptosis, presenting a potential therapeutic approach for glioma.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647163","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}

{"title":"Neuroprotective Potential of Curcumin in Neurodegenerative Diseases: Clinical Insights Into Cellular and Molecular Signaling Pathways","authors":"Md. Rezaul Islam,&nbsp;Abdur Rauf,&nbsp;Sumiya Akter,&nbsp;Happy Akter,&nbsp;Md. Ibrahim Khalil Al-Imran,&nbsp;Md. Naeem Hossain Fakir,&nbsp;Gazi Kaifeara Thufa,&nbsp;Md. Tazul Islam,&nbsp;Hassan A. Hemeg,&nbsp;Waleed Al Abdulmonem,&nbsp;Abdullah S. M. Aljohani,&nbsp;Marcello Iriti","doi":"10.1002/jbt.70369","DOIUrl":"https://doi.org/10.1002/jbt.70369","url":null,"abstract":"<p>Progressive neuronal loss and dysfunction characterize neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, and Huntington's diseases, spinal cord injury, and stroke, making them difficult to treat. Curcumin, a bioactive substance derived from the turmeric plant (<i>Curcuma longa</i>), is interesting due to its potential neuroprotective properties. This review thoroughly shows the cellular and molecular signaling mechanisms that curcumin utilizes to provide neuroprotective effects in NDs. Curcumin regulates several signaling pathways linked to neuroprotection, such as those that reduce oxidative stress, prevent Aβ formation, and decrease neuroinflammation. NF-κB suppression reduces inflammatory responses, while Nrf2 activation boosts antioxidant response element expression. Furthermore, curcumin enhances autophagy and neurotrophic factor expression, facilitating the removal of harmful protein aggregates. The function of curcumin as a metal chelator is emphasized particularly to iron and other metal dysregulations linked to neurodegenerative processes. Curcumin's capacity to regulate metal ion homeostasis is essential since the pathophysiology of NDs is significantly influenced by metal-induced oxidative stress and toxic buildup. It shows potential therapeutic effects by reducing oxidative damage and chelating excess metals. Clinical research indicates that curcumin can penetrate the blood-brain barrier, making it an effective treatment option. The regulation of these pathways reduces neuronal damage and improves neurons' survival and functionality. In addition, curcumin's anti-inflammatory properties and low toxicity make it a promising long-term treatment option for NDs. Therefore, this review emphasizes the potential of curcumin as a targeted neuroprotective compound, presenting recent clinical insights and experimental data. Future studies should optimize curcumin formulations and delivery systems to enhance its bioavailability and therapeutic efficacy.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-Mannose Upregulates Testin via the NF-κB Pathway to Inhibit Breast Cancer Proliferation","authors":"Xue Cao,&nbsp;Xinlan Liu,&nbsp;Ping Chen,&nbsp;Tingting Wei,&nbsp;Qingxia Zhou,&nbsp;Guoxin Zhang,&nbsp;Tong She,&nbsp;Zhisheng Wang,&nbsp;Yaobang Liu","doi":"10.1002/jbt.70398","DOIUrl":"https://doi.org/10.1002/jbt.70398","url":null,"abstract":"<div>\u0000 \u0000 <p><span>d</span>-Mannose is a naturally occurring monosaccharide known to enhance the effects of chemotherapy, immunotherapy, and radiotherapy in cancer patients. This study aimed to investigate the growth-regulating mechanism of <span>d</span>-mannose on breast cancer (BC) cells. <span>d</span>-mannose was treated on MDA-MB-231 and MCF-7 BC cells. Cell counting kit-8 (CCK-8), wound healing test, transwell invasion, and flow cytometry assays were used to assess the viability, invasion, migration, and apoptosis of <span>d</span>-mannose treated BC cells. Testin (TES) expressions in <span>d</span>-mannose treated BC cells were evaluated using western blot analysis, qRT-PCR, and immunofluorescence assays. The potential regulatory relationship between <span>d</span>-mannose and TES in BC cells were explored by analyzing TES gene expression profile in BC cells using the University of California Santa Cruz (UCSC) Xena browser database. Immunohistochemical analysis of TES protein was performed in BC tissue samples obtained from patients. It was found that <span>d</span>-mannose significantly inhibited the growth of MDA-MB-231 and MCF-7 cells in a concentration and time-dependent manner by activating the NF-κB signaling pathway and upregulating TES expression. TES knockdown downregulated the NF-κB1, NF-κB2, and p65 protein expressions. Therefore, this study highlights that <span>d</span>-mannose have the potential to promote anticancer effects upon further trials using in vivo models and clinical studies.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647536","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}

{"title":"WITHDRAWAL: METTL3-Mediated TIM1 Promotes Macrophage M1 Polarization and Inflammation Through IGF2BP2-Dependent Manner","authors":"","doi":"10.1002/jbt.70396","DOIUrl":"https://doi.org/10.1002/jbt.70396","url":null,"abstract":"<p><b>WITHDRAWAL:</b> Xianrong Du, Yinguang Guo, Xiaoqin Zhao, Lijuan Zhang, Ru Fan, Yafeng Li. METTL3-mediated TIM1 promotes macrophage M1 polarization and inflammation through IGF2BP2-dependent manner, Journal of Biochemical and Molecular Toxicology 38, no. 10 (2024): e23845. https://doi.org/10.1002/jbt.23845.</p><p>The above article, published online on 12 September 2024, on Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, the journal Editor-in-Chief, Dr. Hari K. Bhat, and Wiley Periodicals LLC. The withdrawal has been agreed because the article was published without authorisation of all relevant contributors.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvacrol Coadministration Ameliorates Lambda-Cyhalothrin-Induced Peripheral Neuropathy in Rats: Behavioral and Molecular Evidence","authors":"Özge Kandemir,&nbsp;Mustafa İleritürk,&nbsp;Cihan Gür,&nbsp;Nurhan Akaras,&nbsp;Hasan Şimşek,&nbsp;Selçuk Yılmaz,&nbsp;Fatih Mehmet Kandemir","doi":"10.1002/jbt.70400","DOIUrl":"https://doi.org/10.1002/jbt.70400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>This study aimed to investigate the possible neuroprotective effects of Carvacrol (CRV) against Lambda-cyhalothrin (CYH)-induced peripheral neuropathy. Thirty-five rats were divided into five groups: Control, CRV, CYH, CYH+CRV25, and CYH+CRV50. CRV 25 or 50 mg/kg and CYH 6.23 mg/kg were administered orally for 21 days. The effects of these treatments were evaluated by hot plate and rotarod tests, followed by molecular, biochemical, histopathological, and immunohistochemical analyses of sciatic nerve tissues. CYH administration significantly impaired both sensory and motor functions. CRV doses (25 mg/kg and 50 mg/kg) administered with CYH significantly improved these impairments (<i>p</i> &lt; 0.001). Additionally, CYH increased MDA levels and decreased antioxidants, while CRV treatment reversed these effects. CRV also suppressed inflammation (<i>p</i> &lt; 0.01), apoptosis (<i>p</i> &lt; 0.001), and endoplasmic reticulum stress (<i>p</i> &lt; 0.001), with the 50 mg/kg dose being more effective. Morphological and immunohistochemical analyses showed that CRV treatment partially repaired CYH-induced nerve damage, with both doses reducing 8-OHdG and beclin-1 immunoreactions. The data revealed that CYH induced inflammation, oxidative stress, ER stress, and apoptosis in sciatic tissue, while CRV exhibited antioxidant, anti-inflammatory, and antiapoptotic effects, reducing the damage and suggesting its potential as a supportive treatment for CYH-induced sciatic damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGR3 Transcriptionally Upregulates the Expression of DCN in Liver Cancer to Inhibit Tumor Progression","authors":"Hong Yang,&nbsp;Da Sun,&nbsp;Bin Zhang,&nbsp;Chun Yu","doi":"10.1002/jbt.70399","DOIUrl":"https://doi.org/10.1002/jbt.70399","url":null,"abstract":"<div>\u0000 \u0000 <p>Decorin (DCN), a multifunctional extracellular matrix protein, has been reported to exhibit tumor-suppressive effects in various cancers, including liver cancer. However, the transcriptional regulatory mechanisms of DCN in liver cancer remains unclear. We analyzed DCN expression in liver cancer cells using qPCR and Western blot. Functional assays (CCK-8, colony formation, flow cytometry, and Transwell) were performed to assess the effects of DCN overexpression (via pcDNA3.1-DCN) on proliferation, apoptosis, invasion, and migration. Bioinformatics tools (PROMO and UCSC) predicted EGR3 as a potential transcriptional regulator of DCN, which was validated through ChIP and luciferase reporter assays. Rescue experiments (si-EGR3+pcDNA3.1-DCN cotransfection) were conducted to confirm the DCN-EGR3 regulatory axis. DCN was significantly downregulated in liver cancer cells. Its overexpression suppressed proliferation, invasion, and migration while promoting apoptosis. Mechanistically, EGR3 was identified as a transcriptional activator of DCN, and EGR3 knockdown reversed the tumor-suppressive effects of DCN. Our findings demonstrated that DCN exerted antitumor effects in liver cancer via transcriptional activation by EGR3, providing a novel therapeutic target for liver cancer treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624514","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}

{"title":"Blockade of Interferon-Induced Protein 35 Alleviates Cisplatin-Induced Ferroptosis in Acute Kidney Injury Through Activation of the NRF2","authors":"Juan Zhou,&nbsp;Ye Liu,&nbsp;Fang Sun","doi":"10.1002/jbt.70383","DOIUrl":"https://doi.org/10.1002/jbt.70383","url":null,"abstract":"<div>\u0000 \u0000 <p>Ferroptosis is a non-regulatory cell death closely related to the process of cisplatin-induced acute kidney injury (AKI). We sought to explore the ability of inhibited Interferon-induced protein 35 (IFI35) to alleviate cisplatin-induced AKI by modulating ferroptosis. Expression of IFI35 was investigated in the cisplatin-induced AKI mouse model and cisplatin-induced HK2 cells. The potential molecular mechanisms were examined in cells by detecting ferroptosis-related indicators following the addition of ferroptosis inducer (Erastin) and the antioxidant transcription factor NRF2 pathway inhibitor (ML385), respectively. Higher levels of IFI35 were observed in AKI mouse model and HK2 cells. IFI35 deficiency enhanced cell viability and antioxidant capacity, reducing ferroptosis-related parameters like Fe²⁺ accumulation and ROS production while upregulating GPX4 and FSP1 protein levels. In mice, IFI35 blockade attenuated cisplatin-induced renal injury, as evidenced by decreased serum urea nitrogen and creatinine levels, and improved histopathological changes. Mechanistically, IFI35 inhibition reduced peroxide production, reversed iron-dependent mitochondrial damage, and inhibited ferroptosis via upregulating NRF2 activity. Our study suggested that IFI35 inhibition inhibits ferroptosis in AKI by upregulating NRF2 expression, targeting IFI35 may offer a promising therapeutic option for AKI.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615314","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}

{"title":"Elevated BCRP Transporter and Altered NF-кB Pathway Mediate Zoledronic Acid Resistance in MCF-7 Cells","authors":"Öykü Irmak Dikkatli,&nbsp;Yunus Emre Cavlak,&nbsp;Yaprak Dönmez Çakıl,&nbsp;Sueda Atılkan,&nbsp;Erkan Yurtcu,&nbsp;Özlem Darcansoy İşeri","doi":"10.1002/jbt.70397","DOIUrl":"https://doi.org/10.1002/jbt.70397","url":null,"abstract":"<p>Zoledronic acid (ZA), a bisphosphonate derivate, became the standard for preserving bone structure in cancer. Using various intracellular signaling pathways, including NF-κB, ZA inhibits tumor cell proliferation, induces apoptosis, and has additive and synergistic effects with cytotoxic agents. However, it has been observed that resistance has developed against ZA. This study aims to explore the underlying mechanisms of ZA resistance in MCF-7 breast cancer cells by investigating the activity and localization of the human breast cancer resistance protein (BCRP), changes in the NF-κB pathway, and the markers of epithelial-mesenchymal transition (EMT). Previously, MCF-7 cells were stepwise selected in increasing concentrations of ZA and became resistant to 8 µM ZA (MCF-7/Zol). We determined that BCRP levels were elevated with altered intracellular localization in ZA resistant MCF-7 cells, and BCRP pump caused a decrease in the substrate accumulation in the MCF-7/Zol cells whereas no change in intercellular substrate accumulation was observed in parental cells. MCF-7/Zol cells have increased amount of phosphorylated IκB which is associated with increased nuclear translocation of NF-κB. Concordantly, BCRP upregulation may be associated with increased nuclear NF-κB in ZA resistant cells. MCF-7/Zol cells did not harbor EMT markers. Elucidation of molecular mechanisms of resistance developed against chemotherapeutic agents is important to target critical pathways and proteins to eliminate the resistant clones as well as for determining biomarkers for MDR.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin Modulates Expression Pattern of Cancer Multidrug Resistance Proteins in Non-Small Lung Cancer Cell Line","authors":"Khurshid Ahmad Padder","doi":"10.1002/jbt.70394","DOIUrl":"https://doi.org/10.1002/jbt.70394","url":null,"abstract":"<div>\u0000 \u0000 <p>Multidrug resistance (MDR), the most common cause of waning in cancer chemotherapy, hampers the effectiveness of available different anticancer drugs in treating this disease. This MDR is triggered by a class of membrane transporter proteins called ATP-binding cassette (ABC) transporters via drug efflux mechanism which is ATP-dependent. P-glycoprotein (P-gp), an ABC transporter is encoded by the MDR1/ABCB1 gene, is normally involved in the expulsion of toxins from normal cells and also confers resistance to certain chemotherapeutic agents. Inhibition of these membrane bound ABC transporters in drug resistant cells to reverse this MDR mechanism is a well-known approach to enhance the safety and efficacy of cancer chemotherapy. The molecular docking studies between apigenin &amp; P-glycoprotein (P-gp)/ABCB1/MDR1 revealed that apigenin possesses greater binding affinity with transmembrane domain (TMD) region of P-gp/ABCB1/MDR1. In this study, pretreatment with apigenin significantly enhanced antiproliferative effect of PTX in NCI-H460 cells. Comparing Rhodamine-123 (Rh-123) drug efflux mechanism studies among the treatment groups, revealed that apigenin significantly and PTX moderately inhibit transport function when compared to control. Additionally, in comparison to control cells, apigenin treatment drastically decreased the mRNA expression levels of ABCB1/MDR1. Furthermore, expression of ABCB1/MDR1 was found to be downregulated during apigenin treatment. In this study, apigenin enhanced cytotoxicity of PTX in NCI-H460 cells. This might be due to enhanced PTX availability as apigenin inhibits membrane transport function. Thus, the present findings illustrate the modulatory role of apigenin on PTX sensitization in relatively resistant NCI-H460 cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615502","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}

{"title":"SRSF3 Inhibits High Glucose and Palmitic Acid-Induced Cardiomyocyte Apoptosis Through the PI3K/AKT and NF-κB Pathways","authors":"Peng Gao,&nbsp;Shuhua Chen,&nbsp;Hong Xiang,&nbsp;Zhihao Shu,&nbsp;Xuewen Wang,&nbsp;Jing Zhang,&nbsp;Huiqin Liu,&nbsp;Yanfei Chai,&nbsp;Quanjun Liu,&nbsp;Zishun Zhan,&nbsp;Jie Ouyang,&nbsp;Jianing Fan,&nbsp;Xiao Zhang,&nbsp;Xinru Zheng,&nbsp;Jingjing Li,&nbsp;Shiying Qin,&nbsp;Hongwei Lu","doi":"10.1002/jbt.70395","DOIUrl":"https://doi.org/10.1002/jbt.70395","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic cardiomyopathy (DCM) has emerged as a leading cause of mortality among elderly patients with diabetes mellitus (DM). Currently, the pathogenic mechanisms underlying diabetic cardiomyopathy remain elusive. In the present study, we treated with H9C2 cells high glucose (Glu) and palmitic acid (PA) to establish an in vitro model, followed by proteomic profiling. The proteomic analysis revealed that high glucose and palmitic acid levels downregulated the expression of SRSF3. Cell viability was assessed using the CCK-8 assay, whereas flow cytometry and western blot analysis were utilized to analyze cellular apoptosis. Quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) was employed to examine the expression of SRSF3 and western blot analysis was conducted to assess the levels of Bax, Bcl-2, and proteins involved in the PI3K/AKT and nuclear factor (NF)-κB signaling pathways. The TUNEL assay was utilized to measure the myocardial apoptosis rate, and immunofluorescence was employed to evaluate the expression of SRSF3 and pathway proteins in a mice model of diabetic cardiomyopathy. Diabetic cardiomyopathy downregulated the expression of SRSF3, which mediated apoptosis through the PI3K/AKT and NF-κB signaling pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581849","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}