Cell Biochemistry and Function最新文献

{"title":"P2X7 Receptor Facilitates Cardiomyocyte Autophagy After Myocardial Infarction via Nox4/PERK/ATF4 Signaling Pathway","authors":"Shuhong Zhang,&nbsp;Yingying Bi,&nbsp;Kaili Xiang,&nbsp;Yanhong Tang","doi":"10.1002/cbf.70078","DOIUrl":"10.1002/cbf.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial infarction (MI) represents a critical cardiovascular emergency, standing as a leading cause of global mortality. ATP, a typical damage-associated molecular pattern, is stored in cells at high concentrations. Upon cellular injury, hypoxia, or necrosis, substantial quantities of ATP efflux into the extracellular space, activating P2X₇ receptors, thereby initiating multiple signaling cascades. In vivo studies demonstrated coordinated upregulation of P2X₇ and autophagy-related proteins in the infarcted border zone. Transcriptome sequencing revealed Nox4 overexpression in the myocardial tissue post-infarction; furthermore, administration of the P2X₇ receptor antagonist A740003 effectively reduced both autophagy-related protein levels and Nox4 expression. In vitro experiments indicated that hypoxia induced upregulation of Nox4, p-PERK/PERK, ATF4, Beclin-1, and ATG5 in cardiomyocytes, A740003 could inhibit the expression of these proteins, while overexpression of Nox4 counteracted this effect. Collectively, our findings indicated that the P2X₇ receptor expression was elevated in the infarcted border zone following MI and implicated its role in excessive autophagy induced by hypoxia in cardiomyocytes—at least partially through the Nox4/PERK/ATF4 pathway, thereby exacerbating myocardial injury following MI.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actin Gamma Smooth Muscle 2 Promotes Epithelial Ovarian Cancer Cell Proliferation via the AKT1/NF-κB Signaling Pathway","authors":"Yinjue Yu,&nbsp;Jiangxia Li,&nbsp;Xiaohang Wang,&nbsp;Xiaoxiao Li,&nbsp;Cuiting Lyu,&nbsp;Lina Yang,&nbsp;Yongrui Bai","doi":"10.1002/cbf.70077","DOIUrl":"10.1002/cbf.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Epithelial ovarian cancer (EOC) is associated with high mortality rates worldwide and is characterized as the most lethal gynecological cancer. The study aimed to investigate the functional role and underlying molecular mechanism of actin gamma smooth muscle 2 (<i>ACTG2</i>) in the progression of EOC. Data mining from The Cancer Genome Atlas (TCGA) databases showed the expression of <i>ACTG2</i> was significantly upregulated in EOC and negatively associated with longer overall survival and better prognosis of patients. By using of gain-of-function and loss-of-function experiments in vitro and in vivo, we found that ACTG2 promoted EOC cell proliferation and suppressed cell apoptosis. Mechanistic study revealed that ACTG2 regulates EOC cell proliferation by activating the AKT serine/threonine kinase 1 (AKT1)/nuclear factor-κB (NF-κB) signaling pathway. Importantly, p65 plays a crucial role in this newly identified regulatory mechanism. Our findings demonstrate that ACTG2 may play an oncogenic role in EOC, suggesting its potential as a therapeutic target.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Organ Proteome Analysis Reveals Changes in Protein Expression Related With Glucose and Amino Acid Metabolism in Muscles and Hearts of Torpid Mice","authors":"Hirotaka Miyamoto,&nbsp;Shingo Ito,&nbsp;Seiryo Ogata,&nbsp;Ryoko Shimojima,&nbsp;Keiko Sato,&nbsp;Tomoko Kadowaki,&nbsp;Ayako Tokunaga,&nbsp;Kayoko Sato,&nbsp;Yukinobu Kodama,&nbsp;Mihoko N. Nakashima,&nbsp;Koyo Nishida,&nbsp;Mikiro Nakashima,&nbsp;Sumio Ohtsuki,&nbsp;Kaname Ohyama","doi":"10.1002/cbf.70076","DOIUrl":"10.1002/cbf.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>Mammals undergoing hibernation or torpor can reduce their metabolic rate. However, the mechanisms of hypometabolism in hibernating animals remain unclear. Analysis of hibernation mechanisms, taking into account commonalities and differences among organs, is essential for a comprehensive understanding of this reduction in physiological activity. Therefore, we investigated and compared changes in protein expression in the hearts and skeletal muscles of torpid mice using quantitative proteomics. Most of the 108 proteins commonly decreased in both tissues were related to translation, and the decrease in protein expression under torpid conditions was greater in muscle than in the heart. Furthermore, glycolysis related to proteins and pyruvate dehydrogenase expression was significantly decreased only in skeletal muscle. In contrast, only three proteins had significantly increased expression in the heart and muscles, with pyruvate dehydrogenase kinase 4 being the most increased. These results suggested that glucose consumption was reduced under torpid conditions. Our results suggest that the heart and muscles respond to low nutritional levels during torpor by reducing glucose and amino acid consumption to preserve energy. Moreover, this adaptation occurs more strongly in skeletal muscle than in the heart.</p>\u0000 </div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydrodiisoeugenol Alleviates Sodium Palmitate-Induced Mitochondrial Dysfunction and Activates Autophagy in VSMCs via the SIRT1/Nrf2 Axis","authors":"Zhiyun Shu,&nbsp;Wenqing Zhang,&nbsp;Mengze Sun,&nbsp;Zixu Huyan,&nbsp;Shishun Xie,&nbsp;Hongyuan Cheng,&nbsp;Xiangjun Li","doi":"10.1002/cbf.70074","DOIUrl":"10.1002/cbf.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>A high-fat model utilizing sodium palmitate (PA) to inhibit vascular smooth muscle cells (VSMCs) was established to evaluate to evaluate the effects of Dehydrodiisoeugenol (Deh) treatment. Proliferative viability was assessed using the CCK8 and EdU assays, while cell migration and autophagy were analyzed via wound healing and Transwell assays, well as the MDC assay. Oxidative stress was measured through reactive oxygen species staining, and superoxide dismutase (SOD) activity was assessed spectrophotometrically. The malondialdehyde (MDA) content was determined using a colorimetric assay. Mitochondrial function was evaluated through membrane potential analysis, and apoptosis was detected using flow cytometry. Bioinformatics and molecular docking studies identified key targets of Deh in treating atherosclerosis (AS), exploring its role in activating autophagy and inhibiting apoptosis through modulation of SIRT1. The results of this study demonstrated that PA significantly inhibited autophagy in VSMCs, suppressed cell proliferation and migration, and promoted oxidative stress, mitochondrial dysfunction, and apoptosis. In contrast, treatment with Deh significantly ameliorated the PA-induced functional impairment of VSMCs. Furthermore, bioinformatics and molecular docking revealed a strong interaction between Deh and SIRT1, suggesting that SIRT1 may serve as a direct therapeutic target for treating AS. The results of the rescue experiments confirmed the relationship between Deh and SIRT1. Compared to Deh administration alone, the combination of Deh with SIRT1 overexpression (OE) further enhanced the proliferation, migration and autophagy of VSMCs while inhibiting oxidative stress, mitochondrial dysfunction, and apoptosis. Additionally, the effects of Deh were reversed by small interfering RNA targeting SIRT1 (si-SIRT1). The Western blot results indicated that Deh could regulate the expression of both SIRT1 and Nrf2, suggesting that the SIRT1/Nrf2 pathway may be involved in the Deh's signaling mechanism. Deh activate autophagy inhibited by PA in VSMCs and mitigates PA-induced mitochondrial dysfunction and apoptosis in these cells through the SIRT1/Nrf2 signaling axis.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosmarinus officinalis Ethanolic Extracts Rescues BV-2 Cells via Modulating Inflammation and Redox Balance: Comparative Study With Carnosol and Carnosic Acid","authors":"Hatice Ors,&nbsp;Ebru Alimogullari,&nbsp;Sinem Aslan Erdem,&nbsp;Zubeyir Elmazoglu,&nbsp;Asli F. Ceylan","doi":"10.1002/cbf.70073","DOIUrl":"10.1002/cbf.70073","url":null,"abstract":"<p>Neuroinflammation generally refers to an inflammatory response within the central nervous system caused by various pathological insults, including infection, trauma, ischemia, and toxins. As the brain's sentinel immune cell, microglia are tasked as the first responders to infection or tissue injury and initiating an inflammatory response. The perennial shrub plant <i>Rosmarinus officinalis</i> L. was reported to possess anti-inflammatory, anticancer, anti-nociceptive, antidiabetic, neuroprotective, and antioxidative properties. The present study aimed to investigate the effects of <i>Rosmarinus officinalis</i> ethanolic extracts on the lipopolysaccharide (LPS)-induced neuroinflammation model of BV-2 cells in comparison to carnosol and carnosic acid, phenolic diterpenes of the plant. Ultrasound-assisted extraction was used to have ethanolic extract of the plant. LPS was used to induce inflammation in BV-2 cells. Tumor necrosis alpha (TNF-α), interleukin 1 beta (IL-1β) secretion, reactive oxygen species (ROS) production, GSH/GSSG ratio, protein carbonyl level, and caspase-3 activity were evaluated. Inflammation induced by LPS was reduced by the ethanolic extract. Both carnosol and carnosic acid decreased the TNF-α and IL-1β levels as well. The ethanolic extract reduced ROS production and protein carbonylation, and increased GSH/GSSG ratio more effectively compared to the effects of carnosol and carnosic acid. Results depicted that caspase-3 activity was reduced by the ethanolic extract and this effect was more pronounced compared to carnosol and carnosic acid. The present study indicates the ethanolic extract of <i>Rosmarinus officinalis</i> rescues BV-2 cells from apoptosis via alleviating inflammation and oxidative stress.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th17 Cells in Cardiovascular Disease","authors":"Ke Yang,&nbsp;Qianqian Liu,&nbsp;Aodi Fan,&nbsp;Hanqing Lin,&nbsp;Xizheng Wang,&nbsp;Tianyi Cui,&nbsp;Guanwei Fan,&nbsp;Lan Li","doi":"10.1002/cbf.70069","DOIUrl":"10.1002/cbf.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent research has shown a strong link between Th17 cells and their cytokine IL-17, and various cardiovascular diseases such as atherosclerosis, myocardial infarction, myocarditis, and arrhythmia. Moreover, Th17 cell signalling is likely to be a key factor in cardiovascular disease. Here, we summarize recent advances in the source, function, regulation, and the effects of Th17 signaling in cardiovascular disease. Research on Th17 will suggest more specific strategies to manipulate these functions. Thus, effective treatment of cardiovascular disease and future clinical treatment will be possible.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron Metabolism and Ferroptosis in Diabetic Kidney Disease","authors":"Fangxin Mu,&nbsp;Ping Luo,&nbsp;Yuexin Zhu,&nbsp;Ping Nie,&nbsp;Bing Li,&nbsp;Xue Bai","doi":"10.1002/cbf.70067","DOIUrl":"10.1002/cbf.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic kidney disease (DKD) is a major diabetic microvascular complication that still lacks effective therapeutic drugs. Ferroptosis is a recently identified form of programmed cell death that is triggered by iron overload. It is characterized by unrestricted lipid peroxidation and subsequent membrane damage and is found in various diseases. Accumulating evidence has highlighted the crucial roles of iron overload and ferroptosis in DKD. Here, we review iron metabolism and the biology of ferroptosis. The role of aberrant ferroptosis in inducing diverse renal intrinsic cell death, oxidative stress, and renal fibrosis in DKD is summarized, and we elaborate on critical regulatory factors related to ferroptosis in DKD. Finally, we focused on the significance of ferroptosis in the treatment of DKD and highlight recent data regarding the novel activities of some drugs as ferroptosis inhibitors in DKD, aiming to provide new research targets and treatment strategies on DKD.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen G-Protein Coupled Receptor Antagonist G15 Promotes Tau Clearance in 2D and 3D Tauopathy Models","authors":"Michele Sayuri Nishino,&nbsp;Angélica Jardim da Costa,&nbsp;Taysa Bervian Bassani,&nbsp;Roberta Sessa Stilhano,&nbsp;Rodrigo Portes Ureshino","doi":"10.1002/cbf.70072","DOIUrl":"10.1002/cbf.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Several studies have investigated the efficacy of estrogen in age-related diseases, showing promising results in several models of neurodegeneration, such as Alzheimer's disease. Animal and cellular models indicate that estrogen and related compounds can reduce the accumulation of amyloid plaques and tau protein, which are associated with Alzheimer's disease. Therefore, it is crucial to develop appropriate models to study the neuroprotective effects of estrogen, and three-dimensional (3D) models have recently emerged as a viable alternative to animal testing. This study aimed to investigate the potential of 3D tauopathy models for drug testing, focusing on estrogen-related signaling. The results demonstrate that a scaffold-free neurospheroid with inducible tau protein expression allows for the observation of tau protein distribution throughout the spheroid. Moreover, the study found that the G-protein-coupled estrogen receptor antagonist, G15, reduced tau protein concentration in both 2D and 3D models. Thus, this study highlights the importance of estrogen-related compounds in 3D cultures, which could facilitate investigations into the mechanisms of action and the neuroprotective role of estrogen in neurodegenerative diseases.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSD3: A Promising Target for Cancer Therapy","authors":"Ting Huang,&nbsp;Bowen Zhang,&nbsp;Yifan Yang,&nbsp;Qiong Lin,&nbsp;Genbao Shao","doi":"10.1002/cbf.70071","DOIUrl":"10.1002/cbf.70071","url":null,"abstract":"<div>\u0000 \u0000 <p>Over the past 24 years, nuclear receptor-binding SET domain protein 3 (NSD3) has emerged as a critical regulator of cellular physiological processes. As a histone methyltransferase targeting H3K36, NSD3 catalyzes the addition of methyl groups to histone residues, a process that profoundly influences genome imprinting, gene transcription, and genome stability, thereby modulating gene expression. Amplification, mutations, and fusion events involving the <i>NSD3</i> gene have been strongly linked to the pathogenesis of various cancers, highlighting its role as a key regulator of tumorigenesis. This review provides an overview of the general structure and biological functions of NSD3, followed by an analysis of NSD3's role in relation to the hallmarks of cancer as described by Hanahan and Weinberg. Targeting NSD3 has become a major focus of research, with significant efforts directed toward the development and clinical application of NSD3 inhibitors. However, challenges related to specificity and selectivity have hindered progress in this area. Despite these obstacles, the successful development and clinical advancement of other histone methyltransferase inhibitors have provided encouragement to researchers, driving the active pursuit of NSD3-targeted therapies for cancer treatment.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing the Role of Endocannabinoid Receptor Cnr1 in Mouse Ovarian Granulosa Cells","authors":"Jasmine Randhawa,&nbsp;Ejimedo Madogwe,&nbsp;Aire McCall,&nbsp;Jaswinder Singh,&nbsp;Raj Duggavathi","doi":"10.1002/cbf.70070","DOIUrl":"10.1002/cbf.70070","url":null,"abstract":"<p>The endocannabinoid receptors Cnr1 and Cnr2 have been found in reproductive organs such as the oviduct and uterus. These receptors bind to endocannabinoids, the arachinodoylethanolamine (AEA) and arachinodoylglycerol (2-AG), respectively. Both cannbinoid receptors have been investigated for their role in implantation and fertilization. However, not much is explored in terms of their role in ovarian granulosa cells. As these two receptors (especially Cnr1) have affinity towards the major component of Cannabis, tetrahydrocannabinol (THC), its usage raises concerns about the potential effects of THC on ovarian functions. Hence, it is important to characterize the role of endocannabinoid system in the ovarian granulosa cells. The objectives of this study were to use the mouse model to: (1) profile the expression pattern of the <i>Cnr1</i> and <i>Cnr2</i> and the endocannabinoid metabolizing enzymes (<i>Faah</i> and <i>Mgll</i>) in granulosa cells and (2) to determine the effect of the Cnr1 antagonist, AM251 on ovarian functions. We found that <i>Cnr1</i> transcript abundance was higher (<i>p</i> &lt; 0.05) at 4 h hCG than 24 h and 48 h eCG timepoints, whereas <i>Cnr2</i> transcript decreased (<i>p</i> &lt; 0.05) with follicular development. Conversely, <i>Faah</i> and <i>Mgll</i> transcripts were higher at 14 h hCG (<i>p</i> &lt; 0.05) suggesting their upregulation after ovulation. The ovulation rate was lower in AM251 than vehicle-treated mice (<i>p</i> &lt; 0.05), indicating that <i>Cnr1</i> signaling may regulate ovulation. Further investigating the effect of AM251, we found that it significantly downregulated <i>Ptgs2</i> and <i>Pappa</i> (<i>p</i> &lt; 0.05). Overall, these data suggest that Cnr1, an important player in the endocannabinoid system, is important for ovulation.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}