Dareuosh Shackebaei, Kheirollah Yari, Nader Rahimi, Sara Gorgani, Fatemeh Yarmohammadi
{"title":"Targeting the NLRP3 by Natural Compounds: Therapeutic Strategies to Mitigate Doxorubicin-Induced Cardiotoxicity.","authors":"Dareuosh Shackebaei, Kheirollah Yari, Nader Rahimi, Sara Gorgani, Fatemeh Yarmohammadi","doi":"10.1007/s12013-025-01723-4","DOIUrl":"https://doi.org/10.1007/s12013-025-01723-4","url":null,"abstract":"<p><p>Doxorubicin (DOX), a widely utilized anthracycline chemotherapy agent, is known for its potent anticancer efficacy across various malignancies. However, its clinical use is considerably restricted due to the risk of dose-dependent cardiotoxicity, which can lead to long-term heart dysfunction. The underlying mechanism of DOX-induced cardiotoxicity has been associated with the formation of reactive oxygen species (ROS) and disrupting cellular signaling pathways. This is particularly relevant to the activation of the NLRP3 inflammasome, which triggers inflammation and pyroptosis in cardiac cells. In recent years, there has been growing interest in natural compounds that exhibit potential cardioprotective effects against the adverse cardiac effects of DOX. The present study showed that specific natural compounds, such as honokiol, resveratrol, cynaroside, and curcumin, can confer significant protection against DOX-induced cardiotoxicity through the modulation of NLRP3 inflammasome signaling pathways. In summary, incorporating natural compounds into treatment plans could be a practical approach to improve the safety profile of DOX, thereby protecting cardiac health through the regulation of the NLRP3 pathway.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming-Qiang Chu, Ting-Juan Zhang, Zi-Qi Liu, Qian Yang, Ting-Ting Du, Min-Jie Zhang, Ye Jin, Yong-Jie Cao, Xiang-Mei Wen, Zi-Jun Xu, Yang-Jing Zhao, Jiang Lin, Jun Qian, Jing-Dong Zhou
{"title":"MiR-218 Exhibits Anti-Leukemia Effects by Targeting CTNND2 in Primary Acute Erythroid Leukemia HEL Cells.","authors":"Ming-Qiang Chu, Ting-Juan Zhang, Zi-Qi Liu, Qian Yang, Ting-Ting Du, Min-Jie Zhang, Ye Jin, Yong-Jie Cao, Xiang-Mei Wen, Zi-Jun Xu, Yang-Jing Zhao, Jiang Lin, Jun Qian, Jing-Dong Zhou","doi":"10.1007/s12013-025-01722-5","DOIUrl":"https://doi.org/10.1007/s12013-025-01722-5","url":null,"abstract":"<p><p>Acute erythroid leukemia (AEL) is a rare acute myeloid leukemia (AML) subtype that is highly aggressive and is associated with a poor prognosis. Notably, the blockage of erythroid differentiation represents a significant factor in the pathogenesis of erythroleukemia. Prior studies indicated that miR-218 inhibited the erythroid differentiation in a chronic myeloid leukemia (CML)-derived erythroleukemia cell line K562. However, functions of miR-218 in primary AEL remains to be elucidated. To address this gap, functions of miR-218 in HEL cells were evaluated through cell differentiation, cell proliferation, colony formation, cell cycle and cell apoptosis experiments. Subsequently, the targeted downstream genes of miR-218 were identified by the transcriptome sequencing and bioinformatic research, of which demonstrated by the dual-luciferase reporter experiment. Finally, the underlying mechanism of miR-218 in leukemogenesis was identified by enrichment analysis and was validated by western blot (WB) assays. Intriguingly, enhanced miR-218 showed no effect on the erythroid differentiation in HEL cells by determination of the expression of erythroid markers including GATA1, KLF1, TFRC and GYPA. However, miR-218 overexpression in HEL cells presented a markedly anti-proliferative and pro-apoptotic effects, inhibited colony formation and G0/G1 arrest. Transcriptome sequencing and bioinformatics analysis revealed that CTNND2 as the candidate gene of miR-218 within its 3'-untranslated region (3'-UTR) could be bonded by it. Reduced expression level of CTNND2 was further demonstrated by quantitative-PCR and WB after miR-218 overexpression in HEL cells. Furthermore, the luciferase report assay revealed that the CTNND2 production was reduced with its 3'-UTR region was bonded by miR-218. In addition, MAPK signaling pathway was identified and validated as the potential functional pathway involved in leukemogenesis caused by miR-218 overexpression in HEL cells. In summary, miR-218 exhibits anti-proliferative and pro-apoptotic functions by targeting CTNND2 and modulating MAPK signaling in HEL cells, yet it has no impact on the erythroid differentiation process.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Computational Development of Allosteric Peptide Inhibitors Targeting LIM Kinases as a Novel Therapeutic Intervention.","authors":"Nagarajan Hemavathy, Sampathkumar Ranganathan, Vetrivel Umashankar, Jeyaraman Jeyakanthan","doi":"10.1007/s12013-025-01718-1","DOIUrl":"https://doi.org/10.1007/s12013-025-01718-1","url":null,"abstract":"<p><p>LIM Kinases (LIMKs) have emerged as critical therapeutic targets in cancer research due to their central role in regulating cytoskeletal dynamics and cell motility via cofilin phosphorylation. Allosteric inhibitors, which bind outside the ATP-binding pocket, offer distinct advantages over ATP-competitive inhibitors, such as increased specificity, reduced off-target effects, and the ability to overcome resistance. This study investigates a series of novel tetrapeptides mimicking the binding mode of TH470, an allosteric LIMK inhibitor, using in silico docking and molecular dynamics simulations to identify potential lead compounds with high specificity, binding affinity, and favorable pharmacokinetic properties. Structural analyses revealed critical interactions between TH470 and LIMKs, particularly with conserved residues such as Thr405 (gatekeeper residue), Ile408 (hinge region), and Asp469 (XDFG motif), which are essential for stabilizing inhibitor binding. Molecular dynamics simulations confirmed the stability of TH470-LIMK1 and TH470-LIMK2 complexes, with lower RMS deviations and robust interaction patterns enhancing binding affinity. From the set of tetrapeptides mimicking TH470 binding mode, only YFYW, WPHW, and YWFP for LIMK1, and PYWG, FYWV, and WFVW for LIMK2 demonstrated high binding affinities, non-toxic profiles, and promising anti-cancer, anti-angiogenic, and anti-inflammatory properties. Among the studied peptides, LIMK1-YFYW and LIMK2-WFVW exhibited the most substantial binding affinities, supported by high hydrogen bond occupancy with key residues such as Ile416 and Thr405. The findings highlight the therapeutic potential of allosteric peptide inhibitors targeting LIMK-mediated pathways in cancer progression. The study underscores the importance of specific interactions with conserved LIMK residues, providing a foundation for further developing selective inhibitors to modulate actin dynamics and combat cancer-related processes.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nidhi N Shah, Bhavarth P Dave, Kashvi C Shah, Disha D Shah, Kunal G Maheshwari, Mehul R Chorawala
{"title":"Retraction Note: Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution.","authors":"Nidhi N Shah, Bhavarth P Dave, Kashvi C Shah, Disha D Shah, Kunal G Maheshwari, Mehul R Chorawala","doi":"10.1007/s12013-025-01715-4","DOIUrl":"10.1007/s12013-025-01715-4","url":null,"abstract":"","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MLC2: Physiological Functions and Potential Roles in Tumorigenesis.","authors":"Jiaxue Lu, Nan Li, Wenling Zhang","doi":"10.1007/s12013-025-01721-6","DOIUrl":"https://doi.org/10.1007/s12013-025-01721-6","url":null,"abstract":"<p><p>The myosin regulatory light chain 2 (MLC2) is a crucial regulator of myosin activity. Its phosphorylation, mediated by various kinases, plays a vital role in maintaining normal physiological functions in skeletal muscle, myocardium, smooth muscle, and nonmuscle cells. Moreover, MLC2 has been implicated in the development of many cancers through its phosphorylation. An increasing number of studies have shown that MLC2 may influence tumor progression by modulating cancer cell growth, migration, invasion, apoptosis, and autophagy. In this paper, we provide a concise overview of the phosphorylation regulatory mechanisms of MLC2 and its roles in both physiology and tumorigenesis. Furthermore, this study proposes potential directions for future research.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Luisa Alvarez-Chávez, Sergio De Los Santos, Ramón Mauricio Coral-Vázquez, Luis Antonio Reyes-Castro, Elena Zambrano, Patricia Canto
{"title":"Interaction of Programmed Obesity and Postnatal High Fat Diet but Not (-)-Epicatechin Treatment Modifies Muscle Atrophy Proteins Levels in Male Wistar Rats.","authors":"Ana Luisa Alvarez-Chávez, Sergio De Los Santos, Ramón Mauricio Coral-Vázquez, Luis Antonio Reyes-Castro, Elena Zambrano, Patricia Canto","doi":"10.1007/s12013-025-01690-w","DOIUrl":"https://doi.org/10.1007/s12013-025-01690-w","url":null,"abstract":"<p><p>We determine whether the offspring of obese mothers and a postnatal high-fat diet (HFD) modify protein levels related to muscle synthesis (p70S6K-alpha) or atrophy (Murf and MAFbx), and if the administration of (-)-epicatechin (Epi) can modify these alterations. We hypothesized that the ubiquitin ligases Murf and MAFbx would be increased in the obesogenic context, either by in utero obesogenic environment or by a postnatal high-fat diet, while the p70S6K-alpha kinase and its activation might be decreased. Eight groups of six male Wistar offspring formed eight experimental groups: control (C), control fed with HFD (CHFD), maternal obesity (MO), maternal obesity fed with HFD (MOHFD), and the groups with Epi intervention: C+Epi long, CHFD+Epi long, MO+Epi long and MOHFD+Epi long. By Western blot, we evaluated the Epi effect on the Murf, MAFbx, and p70S6K-alpha proteins in gastrocnemius and soleus tissues. The Murf level increased 2.59-fold in CHFD vs C group and 2.62-fold for MOHFD vs C group (p = 0.049 and p = 0.048, respectively) in gastrocnemius tissue. In soleus tissue, we observed an increase of MAFbx (1.52-fold) for the MOHFD group versus the C group (p = 0.049). Epi treatment did not modify any protein expression. In conclusion, we found an increase in the Murf1 protein levels in gastrocnemius tissue of the direct model of obesity; as well, we observed an increase of the Murf1 in gastrocnemius and of the MAFbx in soleus muscles in the group of rats obese by programming and fed postnatally with a high-fat diet (doble stimulus). In addition, since obesity could cause muscle atrophy, which results in impaired muscle function, it would be relevant in future research to evaluate these signaling pathways in animals of different ages in order to search for markers of the progression of diseases such as sarcopenia obesity.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenlin Chen, Zhuocen Cha, Saijun Huang, Ruimin Liu, Jiayi Chen, Peter Muiruri Kamau, Xingjia Lu, Bowen Li, Dequan Liu
{"title":"Recombinant α-Toxin BmK-M9 Inhibits Breast Cancer Progression by Regulating β-Catenin In Vivo.","authors":"Wenlin Chen, Zhuocen Cha, Saijun Huang, Ruimin Liu, Jiayi Chen, Peter Muiruri Kamau, Xingjia Lu, Bowen Li, Dequan Liu","doi":"10.1007/s12013-025-01711-8","DOIUrl":"https://doi.org/10.1007/s12013-025-01711-8","url":null,"abstract":"<p><p>Screening bioactive compounds from natural sources, including animals and plants, is a valuable strategy for identifying novel anti-tumor agents. α-Toxin BmK-M9, a key component of scorpion venom, has received limited attention regarding its potential anti-cancer effects and underlying mechanisms in breast cancer. This study investigates the effects and mechanisms of BmK-M9 in breast cancer using in vitro experiments and a nude mouse model. mRNA sequencing was performed to identify affected signaling pathways, while Western blotting and immunohistochemistry were utilized to analyze the Wnt/β-catenin signaling pathway. The results demonstrated that BmK-M9 significantly inhibited breast cancer cell invasion and migration in vitro and suppressed tumor growth in vivo. Transcriptomic analysis revealed that BmK-M9 influenced cellular processes related to proliferation, apoptosis, motility, and metabolism. Furthermore, BmK-M9 markedly downregulated β-catenin expression in the Wnt/β-catenin pathway. These findings suggest that BmK-M9 exerts anti-tumor effects in breast cancer by modulating Wnt/β-catenin signaling, highlighting its potential as a promising therapeutic candidate.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ameliorative Effect of Rauwolfia vomitoria Ethanol Extract on the Erectile Dysfunction Complicated with Coronary Artery Disease: An In-Vivo and Molecular Docking Approach.","authors":"Hamdalat Folake Muritala, Ridwan Ayinla Abdulrahman, Habeebat Adekilekun Oyewusi, Hashim Ndaman Muhammad","doi":"10.1007/s12013-025-01713-6","DOIUrl":"https://doi.org/10.1007/s12013-025-01713-6","url":null,"abstract":"<p><p>Erectile dysfunction in men may result as a side effect of the use of serotonin reuptake inhibitors such as paroxetine. Enzymes like phosphodiesterase 5 (PDE-5) and arginase are promising therapeutic targets for managing erectile dysfunction while creatinine kinase-myocardial band (CK-MB) serves as a marker for coronary artery disease. To manage these conditions, it is necessary to seek options in medicinal herbs. Rauwolfia vomitoria (RV) is a plant that has been used as an aphrodisiac but the inhibitory mechanism against these enzymes remain unclear. The study used in-vivo enzymatic biomarkers and molecular docking approach to better understand their inhibitory mechanism. Forty-eight adult male Wistar rats were divided into six groups of eight rats: naive control, paroxetine (PXT, 10 mg/kg), PXT+sildenafil citrate (4 mg/kg), PXT + RVE (12.5, 25 and 50 mg/kg). Exposure to PXT lasted for twenty-one days, and treatment with sildenafil citrate and RVE took place for the next seven days. On day twenty-nine, the rats were sacrificed under anaesthesia and various biochemical assays (PDE-5, Arginase, nitric oxide (NO) were carried out on penile tissue homogenate while CK-MB, lipid profile and testosterone were assayed in the serum of rats. This study also employed gas chromatography -flame ionization detection (GC-FID) to identify the phytoconstituents in RV. From our findings, PXT significantly increased PDE-5, Arginase activities with a concomitant decrease in NO concentration. Rauwolfia vomitoria extract (RVE) decreased the activities of the penile PDE 5 and arginase activities, and increased NO concentrations in dose-dependent ways (12.5, 25, and 50 mg/kg body weight). RVE showed an increase in testosterone and a decrease in CK-MB activities. Moreover, the result of lipid profile revealed the significant reversal of the changes caused by PXT administration, indicating the potential of the extract in ameliorating paroxetine-induced dyslipidemia. All of the phytochemicals found by GC-FID docked against PDE-5 had the lowest binding energies ( - 9.4 to -7.0 kcal/mol) when likened to that of sildenafil citrate ( - 7.4 kcal/mol). The phytochemicals were also docked against arginase which released the lowest binding energy between -10.5 and -9.0 kcal/mol when compared with sildenafil citrate ( - 9.4 kcal/mol). This study is relevant in the design of new treatment option for ED and coronary artery disease.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nurgül Abul, Yeliz Demir, Aykut Öztekin, Hasan Özdemir
{"title":"Determination of the Inhibitory Potential of Chalcones on Myeloperoxidase Enzyme Activity: In vitro and Molecular Docking Studies.","authors":"Nurgül Abul, Yeliz Demir, Aykut Öztekin, Hasan Özdemir","doi":"10.1007/s12013-025-01719-0","DOIUrl":"https://doi.org/10.1007/s12013-025-01719-0","url":null,"abstract":"<p><p>Myeloperoxidase (MPO) is a highly abundant hemoprotein in neutrophils and monocytes. It has a crucial function in immunological surveillance and the body's defensive systems. Nevertheless, there is a strong correlation between elevated MPO activity and the development and advancement of inflammatory processes. Chalcone derivatives serve as fundamental components of pharmaceutical raw materials, which have been extensively utilized for the treatment of several ailments. In this study, it was studied the effect of some chalchones on MPO activity. Chalcones (1-6) strongly inhibited MPO with IC<sub>50s</sub> in the micromolar range of 0.05-0.828 µM. In particular, 4,4'-difluorochalcone (3) exhibited the best MPO inhibitory impact with IC<sub>50</sub> of 0.05 µM. Additionally, molecular docking experiments were conducted to predict the binding affinities and interactions of the chalcone derivatives with the MPO active site. The docking results revealed that all tested compounds exhibited favorable binding energies, with ΔG Vina values ranging from -7.6 to -8.4 kcal/mol. Compound 3 demonstrated the strongest binding affinity (-8.4 kcal/mol), forming key hydrogen bonds with Gln91 and His95, and halogen interactions with the fluorine atoms, which may account for its enhanced inhibitory activity. These combined in vitro and in silico results suggest that chalcone derivatives hold significant potential as therapeutic candidates targeting MPO.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"sPLA2-IB and PLA2R Mediate Aberrant Glucose Metabolism in Podocytes via Hyperactivation of the mTOR/HIF-1α Pathway.","authors":"Jiwen Bao, Binbin Dai, Liyan Yang, Zikang Liu, Yuxuan Jin, Hanxue Zhao, Yangbin Pan","doi":"10.1007/s12013-025-01714-5","DOIUrl":"https://doi.org/10.1007/s12013-025-01714-5","url":null,"abstract":"<p><p>Secretory phospholipase A2 group IB (sPLA2-IB) and M-type phospholipase A2 receptor (PLA2R) are closely related to proteinuria and idiopathic membranous nephropathy (IMN). Podocytes are important components of the glomerular filtration barrier and glucose metabolism, including glycolysis and tricarboxylic acid (TCA) cycle, is crucial for maintaining podocyte physiological function. Aberrant energy metabolism has been reported in proteinuria diseases, including diabetic nephropathy. However, altering energy states in podocytes in IMN remain unknown. The study aimed to determine whether sPLA2-IB induces energy metabolism abnormalities in podocytes. Cultured podocytes were treated with sPLA2-IB. siRNAs were used to knockdown expression of HIF-1α and PLA2R. Adenosine triphosphate (ATP) levels, the oxygen consumption rate and lactate content were assessed. Key enzyme of glycolysis, PKM2 and LDHA, TCA cycle-related enzymes and mTOR/HIF-1α pathway, were analyzed by PCR and immunoblotting. MTT assay was used for cell viability and phalloidin for cytoskeleton staining. sPLA2-IB induced insufficient energy states in podocytes, by decreased ATP production, increased lactate accumulation and reduced oxygen consumption rates. Under sPLA2-IB stimulation, LDHA and PKM2 were increased, while TCA cycle-related enzymes (CS, FH and SDHD) were decreased, with upregulated mTOR and HIF-1α. Mechanically, HIF-1α knockdown mitigated sPLA2-IB -induced LDHA upregulation and downregulated TCA cycle-related enzymes. Rapamycin (inhibitor of mTOR) reversed decreased ATP levels and oxygen consumption. 3-MA (activator of mTOR) aggravated lactate production. PLA2R knockdown reversed PKM2 and LDHA upregulation, FH and SDHD downregulation, and increased mTOR and HIF-1α expression. PLA2R activation by sPLA2-IB caused abnormal energy states in podocytes. The underlying mechanism involved the activation of mTOR/HIF-1α pathway.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}