Cell Stress & Chaperones最新文献

Melatonin Mitigates Bisphenol A- and MBP-Induced Damage in Leydig Cells by Alleviating Oxidative Stress and Endoplasmic Reticulum Stress via inhibition of PERK signaling pathway. 褪黑素通过抑制PERK信号通路减轻氧化应激和内质网应激对间质细胞损伤的影响

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-10-15 DOI: 10.1016/j.cstres.2026.100222

Qi Qi, Jijing Xu, Shuang Li, Xiaoyan Pan

{"title":"Melatonin Mitigates Bisphenol A- and MBP-Induced Damage in Leydig Cells by Alleviating Oxidative Stress and Endoplasmic Reticulum Stress via inhibition of PERK signaling pathway.","authors":"Qi Qi, Jijing Xu, Shuang Li, Xiaoyan Pan","doi":"10.1016/j.cstres.2026.100222","DOIUrl":"https://doi.org/10.1016/j.cstres.2026.100222","url":null,"abstract":"<p><p>This study aims to elucidate the protective effects of melatonin against Bisphenol A (BPA) and its metabolite 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP)-induced apoptosis in Leydig cells, focusing on its ability to alleviate oxidative stress and endoplasmic reticulum stress. Results showed that melatonin significantly alleviated testicular damage caused by BPA, increased testicular index in mice, improved the function of seminiferous tubules, and enhanced the survival rate and density of epididymal sperm. Furthermore, melatonin treatment significantly reduced the number and proportion of TUNEL-positive Leydig cells, decreased cleaved caspase-3 expression and the cleaved caspase-3/total caspase-3 ratio, increased testosterone secretion from Leydig cells, and elevated the expression of steroidogenic enzymes cytochrome P450 17α-hydroxylase/20-lyase and 17β-hydroxysteroid dehydrogenase 3. Melatonin also significantly lowered the elevated reactive oxygen species levels in Leydig cells induced by MBP and enhanced the expression of antioxidant enzymes superoxide dismutase 1/2 and catalase. Additionally, melatonin effectively countered endoplasmic reticulum stress in Leydig cells induced by BPA and MBP, significantly decreasing levels of GRP94 and GRP78, while inhibiting activation of the PERK/EIF2α/ATF4/CHOP signaling pathway. Notably, melatonin significantly alleviated endoplasmic reticulum stress and apoptosis in TM3 cells, and this effect was associated with enhanced SIRT1 nuclear localization and deacetylase activity, as demonstrated by reduced acetylated-p53 levels. Collectively, melatonin effectively protects Leydig cells from BPA and MBP-induced damage by alleviating oxidative stress and endoplasmic reticulum stress through inhibition of the PERK signaling pathway, an effect that may involve SIRT1 activation. It may serve as a therapeutic agent to safeguard male reproductive health against environmental pollutants.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"100222"},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191518","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}

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Cover and caption 封面及标题

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-09-01 Epub Date: 2026-09-08 DOI: 10.1016/j.cstres.2026.100213

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Editorial Board Members/Copyright 编辑委员会成员/版权

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-09-01 Epub Date: 2026-09-08 DOI: 10.1016/j.cstres.2026.100214

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Evolution of Hsp90 targeting: From stress biology to clinical translation Hsp90靶向的进化：从应激生物学到临床翻译。

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-07-01 Epub Date: 2026-06-19 DOI: 10.1016/j.cstres.2026.100193

Ilham Zarguan, Lamiae Belayachi, Abdelaziz Benjouad, Ahmed Chadli

{"title":"Evolution of Hsp90 targeting: From stress biology to clinical translation","authors":"Ilham Zarguan, Lamiae Belayachi, Abdelaziz Benjouad, Ahmed Chadli","doi":"10.1016/j.cstres.2026.100193","DOIUrl":"10.1016/j.cstres.2026.100193","url":null,"abstract":"<div><div>Hsp90 inhibitors represent a decades-long experimental framework that has progressively uncovered how molecular chaperone systems are organized, regulated, and rewired in disease. Early natural products established that pharmacologic engagement of Hsp90 simultaneously destabilizes broad client networks and exposes a central layer of proteostasis control. Subsequent structural, biochemical, and translational studies revealed the mechanistic importance of nucleotide-driven conformational cycling, cochaperone exchange, paralog specialization, and subcellular compartmentalization, as well as the emergence of disease-specific chaperone assemblies such as the epichaperome. In parallel, adaptive responses to Hsp90 inhibition, including heat-shock factor 1 activation, unfolded-protein-response signaling, autophagy induction, and oncogenic network rewiring, illuminated the resilience built into proteostasis architecture and the conditions under which it can be overcome. Later inhibitor classes, encompassing C-terminal allosteric ligands, middle-domain modulators, isoform-selective agents, epichaperome-directed compounds, and targeted degraders, extended the field from pan-inhibition toward increasingly precise intervention in specific chaperone states. The first regulatory approval of an Hsp90 inhibitor, Pimitespib, for refractory gastrointestinal stromal tumor, marks a translational milestone that validates this framework clinically. Combination studies have further mapped where Hsp90 inhibition is most informative and most effective, demonstrating that benefit is strongest when deployment is guided by defined client dependency, proteostasis burden, immune context, or biomarker selection. Together, these advances position Hsp90 inhibitor research as a major source of mechanistic insight into molecular chaperones and as a foundation for biomarker-guided, context-aware targeting of proteostasis in oncology and beyond.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 4","pages":"Article 100193"},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276016","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}

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Hspa1b attenuates hypoxia/reoxygenation-induced cardiomyocyte injury through dual suppression of P53-driven apoptotic and ferroptotic pathways Hspa1b通过双重抑制p53驱动的凋亡和嗜铁途径减轻缺氧/再氧诱导的心肌细胞损伤。

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-07-01 Epub Date: 2026-06-24 DOI: 10.1016/j.cstres.2026.100194

Chang Liu, Wensheng Qi, Yue Li, Tingting Fan, Yun Lan, Lei Pang, Haichun Ma, Yin Cai

{"title":"Hspa1b attenuates hypoxia/reoxygenation-induced cardiomyocyte injury through dual suppression of P53-driven apoptotic and ferroptotic pathways","authors":"Chang Liu, Wensheng Qi, Yue Li, Tingting Fan, Yun Lan, Lei Pang, Haichun Ma, Yin Cai","doi":"10.1016/j.cstres.2026.100194","DOIUrl":"10.1016/j.cstres.2026.100194","url":null,"abstract":"<div><div>While the cardioprotective role of heat shock proteins (HSPs) in cardiovascular diseases is well established, the isoform-specific functions of HSP70 members in ischemia-reperfusion (I/R) injury remain unclear. This study investigates the role of Hspa1b, a stress-inducible HSP70 isoform, in cardiac I/R injury and elucidates its underlying mechanisms. <em>In vivo</em>, male C57BL/6 J mice were subjected to myocardial I/R surgery. <em>In vitro</em>, H9C2 cardiomyocytes were transfected with siRNA targeting Hspa1b or p53 and subjected to a hypoxia/reoxygenation (H/R) model. Cellular injury was quantified <em>via</em> lactate dehydrogenase (LDH) release, while viability was assessed using the CCK-8 assay. Apoptotic (Bax, Bcl2, and cleaved Caspase3) and ferroptotic (GPX4, XCT/SLC7A11) markers were analyzed by Western blotting. We found that I/R injury in mouse hearts upregulated Hspa1b and p53 protein levels, accompanied by increased infarct size and elevated plasma CK-MB levels. Similarly, H/R treatment in H9C2 cells increased Hspa1b and p53, which coincided with increased apoptosis and ferroptosis. Knockdown of Hspa1b exacerbated H/R-induced cellular injury, as evidenced by further increases in LDH release and reductions in cell viability, and amplified the changes in apoptotic and ferroptotic markers. Crucially, co-silencing Hspa1b and p53 partially rescued these effects, restoring cell viability and suppressing death pathways. Hspa1b confers cardioprotection against H/R injury by suppressing p53-mediated apoptosis and ferroptosis. These findings identify Hspa1b as a key protective regulator that mitigates I/R injury through dual regulation of cell death pathways.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 4","pages":"Article 100194"},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315945","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}

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Size-dependent internalization of micro- and nanoplastics induces pro-inflammatory and oxidative stress responses in marine and freshwater fish cell lines 大小依赖的微塑料和纳米塑料内化诱导海洋和淡水鱼细胞系的促炎和氧化应激反应。

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-07-01 Epub Date: 2026-07-08 DOI: 10.1016/j.cstres.2026.100195

Kiyun Park, Trang Thi Nguyen, Ihn-Sil Kwak

{"title":"Size-dependent internalization of micro- and nanoplastics induces pro-inflammatory and oxidative stress responses in marine and freshwater fish cell lines","authors":"Kiyun Park, Trang Thi Nguyen, Ihn-Sil Kwak","doi":"10.1016/j.cstres.2026.100195","DOIUrl":"10.1016/j.cstres.2026.100195","url":null,"abstract":"<div><div>Microplastics (MPs) are ubiquitously detected in aquatic ecosystems and represent a growing environmental concern due to their persistence, accumulative toxicity, and ability to cross biological barriers, posing substantial risks to fish species. Although numerous studies have investigated the toxicity of MPs in fish, there is limited data on the potential toxic effects of MP exposure at the cellular level. In this study, we aimed to compare the cellular toxicity of polystyrene MPs of different shapes and sizes in fin and muscle cells derived from marine (red sea bream: PMF) and freshwater (fathead minnow: FHM) fish. Our results showed that exposure to MPs of various shapes and sizes did not cause significant changes in cell viability in either cell line. No significant differences were observed, although exposure to spherical MPs (1 μm) induced a decrease in cell viability at relatively high concentrations. The cellular uptake of MPs was observed following exposure to spherical MPs (0.2 and 1 μm), with internalization occurring at 6 h for 1 μm and 24 h for 0.2 μm of incubation. Internalization efficiency was higher for 1 μm MPs than for 0.2 μm MPs. Exposure to spherical MPs (0.2 and 1 μm) induced alterations in intracellular ROS levels and triggered the up-regulation of the <em>NRF2</em> gene, a transcription factor involved in the stress response. The expression of pro-inflammatory cytokines, including <em>TNF-α</em> and <em>IL1-β</em>, was increased by exposure to spherical MPs (0.2 and 1 μm). In addition, this exposure changed the transcriptional responses of immune defense-related genes. Overall, our results suggest that acute exposure to spherical MPs (0.2 and 1 μm) may be related to the disruption of the immune defense system through continuous inflammation at the cellular level in fish, although it does not directly affect cell viability.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 4","pages":"Article 100195"},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410474","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}

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Insights into the function and structure of the R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) chaperone complex 深入了解R2TP伴侣复合体的功能和结构。

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-07-01 Epub Date: 2026-06-04 DOI: 10.1016/j.cstres.2026.100192

Maryama Mohamed, Ruikai Wu, Walid A. Houry

{"title":"Insights into the function and structure of the R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) chaperone complex","authors":"Maryama Mohamed, Ruikai Wu, Walid A. Houry","doi":"10.1016/j.cstres.2026.100192","DOIUrl":"10.1016/j.cstres.2026.100192","url":null,"abstract":"<div><div>The R2TP chaperone complex comprises two AAA+ proteins, RUVBL1 and RUVBL2, along with RPAP3 and PIH1D1. R2TP functions in concert with other chaperones, such as HSP90 and HSP70, to facilitate the assembly of macromolecular complexes integral to the regulation of cell growth and proliferation. Moreover, several adaptors interact with R2TP to impart substrate specificity. Nevertheless, the precise mechanism underlying R2TP-mediated complex assembly remains unknown. This review summarizes the current knowledge regarding R2TP’s involvement in the assembly, stabilization, and activity of multiple protein complexes, including box C/D and H/ACA small nucleolar ribonucleoproteins (snoRNPs), spliceosome small nuclear ribonucleoproteins (snRNPs), the tuberous sclerosis complex (TSC) , axonemal dynein arms, RNA polymerases, phosphatidylinositol 3-kinase-related kinases (PIKK), and the MRE11-RAD50-NBS1 (MRN) complex. Additionally, the role of R2TP in ciliogenesis, circadian rhythm regulation, and transcriptional condensate formation is discussed. Finally, the latest structural studies pertaining to R2TP and its related complexes are examined.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 4","pages":"Article 100192"},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175586","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}

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Editorial Board Members/Copyright 编辑委员会成员/版权

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-07-01 Epub Date: 2026-07-23 DOI: 10.1016/j.cstres.2026.100198

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Cover and caption 封面及标题

IF 4.1 3区生物学

Cell Stress & Chaperones Pub Date : 2026-07-01 Epub Date: 2026-07-23 DOI: 10.1016/j.cstres.2026.100197

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Nucleotide-dependent domain interactions of Aha1-type co-chaperones with Hsp90 reveal evolutionarily conserved binding determinants aha1型共伴侣蛋白与Hsp90的核苷酸依赖结构域相互作用揭示了进化上保守的结合决定因子。

IF 3.2 3区生物学

Cell Stress & Chaperones Pub Date : 2026-05-01 Epub Date: 2026-04-21 DOI: 10.1016/j.cstres.2026.100179

Desmond Prah Amoah , Rakesh Bhat , Malak Trad , Solomon K. Hussein , Michael Overduin , Paul LaPointe

{"title":"Nucleotide-dependent domain interactions of Aha1-type co-chaperones with Hsp90 reveal evolutionarily conserved binding determinants","authors":"Desmond Prah Amoah , Rakesh Bhat , Malak Trad , Solomon K. Hussein , Michael Overduin , Paul LaPointe","doi":"10.1016/j.cstres.2026.100179","DOIUrl":"10.1016/j.cstres.2026.100179","url":null,"abstract":"<div><div>Hsp90 is a dimeric molecular chaperone essential for the maturation, activation, stabilization, and folding of numerous clients required for cellular functions. Hsp90 progresses through a dynamic ATP-driven conformational cycle that is precisely regulated by accessory proteins known as co-chaperones. Here, we show that the isolated N-domain of Aha1 (Aha1N156) binds the apo state of Hsp90 but fails to associate with the closed, nucleotide-bound state. In contrast, the full-length Aha1 binds Hsp90 in both conformational states, suggesting a key role for the Aha1 C domain in binding to the nucleotide-bound, closed state of Hsp90. Surprisingly, the Aha1 paralogue Hch1, which corresponds to the Aha1 N domain, was capable of binding to Hsp90 in both the apo and nucleotide-bound states. Interestingly, the addition of a 14 amino acid residues section of the linker to the Aha1 N domain restores closed-state binding, indicating an unexpected role for the linker in stabilizing nucleotide-dependent interactions. Analysis of yeast-human Aha1 chimeras further demonstrates that the C-terminal domain of Aha-type co-chaperones serves as an evolutionarily conserved anchoring module, enabling stable engagement of the ATP-bound state despite significant sequence divergence. This work allows us to propose a model in which the Aha1 C domain allows for the repositioning of the Aha1 N domain that occurs during the transition from the apo to the ATP-bound state of Hsp90.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 3","pages":"Article 100179"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763451","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}

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