Cell Stress & Chaperones最新文献

{"title":"Corrigendum to “The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury” [Cell Stress Chaperones. 2025;30(3):160-171]","authors":"Ting Liu , Lu Li , Meixia Meng , Ming Gao , Jinhua Zhang , Yuan Zhang , Yukun Gan , Yangjie Dang , Limin Liu","doi":"10.1016/j.cstres.2025.100094","DOIUrl":"10.1016/j.cstres.2025.100094","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100094"},"PeriodicalIF":3.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722548","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":"In vivo Imaging of Heat shock protein 90: diagnostic tool and support for Hsp90 targeted Therapy.","authors":"Romy Cools, Koen Vermeulen, Guy Bormans","doi":"10.1016/j.cstres.2025.100105","DOIUrl":"https://doi.org/10.1016/j.cstres.2025.100105","url":null,"abstract":"<p><p>The molecular chaperone Heat shock protein 90 (Hsp90), essential for protein homeostasis and cellular stress response, has emerged as a promising therapeutic target across various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions. Although numerous Hsp90 inhibitors have been developed and extensively evaluated in clinical studies, progress has been impeded by limited clinical efficacy, narrow therapeutic windows, and challenges in assessing target engagement. These limitations highlight the importance of developing complementary non-invasive molecular imaging tools to better understand Hsp90 function in vivo and optimize therapeutic strategies, including assessing target engagement, refining dosing strategies, monitoring treatment response, and enabling patient stratification. This review provides a comprehensive overview of the current landscape of Hsp90-targeted molecular imaging. We discuss imaging modalities applicable to Hsp90, optical imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET), and highlight key molecular probes developed to visualize Hsp90 expression and function in vivo using these modalities. Furthermore, we summarize significant findings that have deepened our fundamental understanding of Hsp90's role in disease, supported the development of novel therapeutic approaches, demonstrated imaging effectiveness in preclinical models, and suggested potential for integration into clinical research. We also address current challenges and propose future directions for the field. Through this review, we aim to illustrate the translational potential of molecular imaging in advancing our understanding of Hsp90 in disease and optimizing Hsp90-targeted therapeutics, thereby contributing to precision medicine approaches.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"100105"},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728276","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":"Gangliosides and cholesterol, two major components of the membrane lipid rafts, as new regulatory partners for stress granules assembly","authors":"Anaïs Aulas,&nbsp;Coralie Di Scala","doi":"10.1016/j.cstres.2025.100093","DOIUrl":"10.1016/j.cstres.2025.100093","url":null,"abstract":"<div><div>Stress granules are cytoplasmic inclusions with cyto-protective functions assembling in response to stress. They are now accepted to be part of the pathological mechanism in several diseases, from cancer to neurodegenerative disorders. However, the field is still struggling to find common regulators of their assembly and function. In this study, we describe a mechanism involving lipid rafts (gangliosides and cholesterol), in the regulation of stress granules formation. This study reports that membrane lipid composition is able to regulate the formation of stress granules potentially unraveling several disease mechanisms.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100093"},"PeriodicalIF":3.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682110","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":"Heat-induced phosphatidylserine changes drive HSPA1A's plasma membrane localization","authors":"Jensen Low ,&nbsp;Rachel Altman ,&nbsp;Allen Badolian ,&nbsp;Azalea Blythe Cuaresma ,&nbsp;Carolina Briseño ,&nbsp;Uri Keshet ,&nbsp;Oliver Fiehn ,&nbsp;Robert V. Stahelin ,&nbsp;Nikolas Nikolaidis","doi":"10.1016/j.cstres.2025.100092","DOIUrl":"10.1016/j.cstres.2025.100092","url":null,"abstract":"<div><div>HSPA1A is a molecular chaperone crucial in cell survival. In addition to its cytosolic functions, HSPA1A translocates to heat-shocked and cancer cells' plasma membrane (PM). In cancer, PM-localized HSPA1A (mHSPA1A) is associated with increased tumor aggressiveness and therapeutic resistance, suggesting that preventing its membrane localization could have therapeutic value. This translocation depends on HSPA1A's interaction with PM phospholipids, including phosphatidylserine (PS). Although PS binding regulates HSPA1A's membrane localization, the exact trigger for this movement remains unclear. Given that lipid modifications are a cancer hallmark, we hypothesized that PS is a crucial lipid driving HSPA1A translocation and that heat-induced changes in PS levels trigger HSPA1A's PM localization in response to heat stress. We tested this hypothesis using pharmacological inhibition and RNA interference targeting PS synthesis, combined with confocal microscopy, lipidomics, and western blotting. Lipidomic analysis and PS-specific biosensors confirmed a heat shock-induced PS increase, peaking immediately post-stress. Inhibition of PS synthesis with fendiline and RNA interference significantly reduced HSPA1A's PM localization, while depletion of cholesterol or fatty acids had minimal effects, confirming specificity for PS. Further experiments showed that PS saturation and elongation changes did not significantly impact HSPA1A's PM localization, indicating that the total PS increase, rather than specific PS species, is the critical factor. These findings reshape current models of HSPA1A trafficking, demonstrating that PS is a crucial regulator of HSPA1A's membrane translocation during the heat shock response. This work offers new insights into lipid-regulated protein trafficking and highlights the importance of PS in controlling cellular responses to stress.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100092"},"PeriodicalIF":3.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625463","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":"HSPA2 Emerges as a Key Biomarker: Insights from Global Lysine Acetylproteomic Profiling in Idiopathic Male Infertility.","authors":"Lisa Goutami, Soumya Ranjan Jena, Ajaya Kumar Moharana, Anwesha Pradhan, Sujata Kar, Luna Samanta","doi":"10.1016/j.cstres.2025.100090","DOIUrl":"https://doi.org/10.1016/j.cstres.2025.100090","url":null,"abstract":"<p><p>Spermatozoa are highly specialized cells, and any alterations in their protein profiles may affect their function and fertilizing ability. In spermatozoa, which are transcriptionally and translationally inactive, molecular chaperones particularly heat shock proteins play crucial roles in maintaining redox balance and preserving protein integrity. Post-translational modifications, particularly lysine acetylation, influence chaperone function and are lately being recognized in the pathophysiology of male infertility. To assess the impact of lysine acetylation on sperm chaperone proteins in idiopathic infertile patients (IIP) compared to fertile donors (FD), we performed immunoprecipitation coupled with LC-MS/MS analysis of lysine acetylated sperm proteins from both groups. Proteomic analysis revealed 2,988 acetylated proteins, comprising 26 chaperone proteins that were differentially expressed with four upregulated and nine downregulated in the IIP group. Functional analyses demonstrated enrichment of these proteins in protein folding, spermatogenesis, and response to oxidative stress. CytoHubba analysis reported, key HSP70 family members, HSPA2, HSPA4, and HSPA1A as central hub proteins in protein-protein interaction networks. STRING and IPA network analyses further highlighted the central regulatory roles of these chaperones, with HSPA2 emerging as a key hub protein based on friendship analysis. Western blot validation revealed hypoacetylation and downregulation of HSPA2 in spermatozoa from the IIP group, accompanied by elevated levels of 4-Hydroxynonenal (4-HNE), indicating a link between redox imbalance and altered lysine acetylation in chaperone proteins. Additionally, intense aniline blue staining of sperm nuclei in the IIP group suggested aberrant spermiogenesis. Considering HSPA2's well-documented involvement in sperm maturation and oocyte recognition, its diminished acetylation and expression may not only act as a potential biomarker but also contribute mechanistically to the development of idiopathic male infertility. This study underscores the significance of lysine acetylation in HSPA2 in regulating chaperone function and highlights its diagnostic and therapeutic potential in unexplained male infertility.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"100090"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616472","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":"Combined approaches to reduce stress and improve livestock well-being: A review","authors":"Ariel Shabtay","doi":"10.1016/j.cstres.2025.100091","DOIUrl":"10.1016/j.cstres.2025.100091","url":null,"abstract":"<div><div>It is well established that various stressors confer hazardous impact on the welfare, health, productive, and reproductive efficiencies of farm animals. Among the major stress stimuli, temperature, transportation, weaning, pathogens, diet quality, and routine handling are cardinal in causing diminished performance of livestock. It is hypothesized that the key to reducing disease incidence and animal discomfort appears to be centered at reducing their response to stress. To this end, strategies that involve thermal conditioning at an early age, dietary interventions, and identification of genetic and biochemical biomarkers to predict the risk for developing stress-related diseases an early, have been studied by our research team during the last two decades as means to alleviate stress in Aves and ruminants. The findings from these studies are presented here to illustrate how the applied strategies have contributed to the following outcomes: 1. In layer hens: Improved regulation of body temperature, reduced mortality rates, and a delayed onset of heat shock protein induction. 2. In cattle: a. mitigation of intestinal diseases and prevention of blood parasite invasion; b. identification of genomic and proteomic biomarkers predictive of susceptibility to bovine respiratory disease, the leading cause of morbidity and mortality among young cattle globally.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100091"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616471","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":"Editorial Board Members/Copyright","authors":"","doi":"10.1016/S1355-8145(25)00043-4","DOIUrl":"10.1016/S1355-8145(25)00043-4","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100098"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686614","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":"The effect of heat stress on the physiological parameters and blood biomarkers in Malabari goats","authors":"Prasannan Gopikrishnan ,&nbsp;Roshin Anie Jose ,&nbsp;John Abraham ,&nbsp;Devasia Kaithakulam Deepak Mathew ,&nbsp;Kanakkaparambil Raji ,&nbsp;Nalukudy Paramba Sakkariya Ibrahim ,&nbsp;Packirisamy Valavan ,&nbsp;Thaliyakulam Suresh Nisha ,&nbsp;Varun Vijayan","doi":"10.1016/j.cstres.2025.100082","DOIUrl":"10.1016/j.cstres.2025.100082","url":null,"abstract":"<div><div>Heat stress poses a great challenge to livestock health, productivity, and adaptability, especially in tropical climates. Under the scenario of climate change and rising global temperatures, understanding the physiological, hematological, biochemical, and molecular responses to heat stress in livestock is crucial. The present study was designed to assess the physiological, hematological, biochemical, and molecular responses to heat stress in the Malabari goat breed, which originated in South India. The gene expression patterns of heat-shock proteins (HSPs) <em>HSP27</em>, <em>HSP70</em>, and <em>HSP90</em> were also assessed. Twelve adult does were divided into grazing and nongrazing groups, and the study was conducted for 2 months during winter and summer seasons. Higher ambient temperature and solar radiation were recorded in summer, with a higher temperature-humidity index indicating heat stress (77.50 ± 0.27). Significant increases in respiratory rate, rectal temperature, and surface body temperature were detected in goats, indicating that the animals were under physiological stress, especially during the summer season. The seasonal changes in these parameters differed between grazing and nongrazing goats. The pulse rate was significantly influenced by both season and grazing patterns. The hematological parameters like monocyte count, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration in Malabari goats were mainly influenced by seasonal variations. However, the seasonal shift in hematocrit levels was not uniform across the grazing strategies. Biochemical parameters, including aspartate aminotransferase and alanine aminotransferase (ALT) levels, exhibited significant seasonal variations. Additionally, ALT and total protein concentrations differed between the grazing groups. The impact of seasonal variations on glucose concentration varied between grazing and nongrazing goats. <em>HSP70</em> and <em>HSP90</em> gene expression increased over the summer, but <em>HSP27</em> gene expression did not show any difference in our study. As a stress response mechanism, these results show that Malabari goats experience physiological, hematological, biochemical, and molecular changes in response to heat stress, including the upregulation of important HSPs.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100082"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076224","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":"Hypoxia- and mechanical stress–induced upregulation of mitochondrial HSP60 is associated with phenotypic switching of pulmonary arterial smooth muscle cells","authors":"Geng Liu ,&nbsp;Han Nie ,&nbsp;Xu Zhang ,&nbsp;Zi-Sheng Huang ,&nbsp;Koh-Ichiro Yoshiura ,&nbsp;Ke-Xiang Liu ,&nbsp;Yi Liu ,&nbsp;Tao-Sheng Li","doi":"10.1016/j.cstres.2025.100089","DOIUrl":"10.1016/j.cstres.2025.100089","url":null,"abstract":"<div><h3>Background</h3><div>Switching from a contractile to a synthetic phenotype of pulmonary arterial smooth muscle cells (PASMCs) is known to play a crucial role in pulmonary arterial hypertension (PAH). We investigated how hypoxia and mechanical stress mediate the phenotypic switching of PASMCs.</div></div><div><h3>Methods</h3><div>Human PASMCs were used for experiments. Hypoxia treatment was done by culturing cells under 1% O₂. Mechanical stress was induced by loading cells to 50 mmHg hydrostatic pressure. We analyzed cell morphology, cell proliferation, phenotypic marker protein expression, cytokine release, and the activation of stress-related pathways at 24 h after treatment. Bulk and single-cell RNA-sequencing datasets were used to analyze heat shock protein family D member 1 (HSPD1) expression in PAH lungs and PASMCs. Heat shock protein 60 (HSP60) was knocked down in PASMCs by transfection of HSPD1-siRNA.</div></div><div><h3>Results</h3><div>Either hypoxia or mechanical stress alone induced the morphology change, increased cell proliferation, and promoted the phenotypic switching and inflammatory cytokines release of PASMCs. Interestingly, all those were dramatically enhanced under the combination of hypoxia and mechanical stress. Mechanistically, we found that the combination of hypoxia and mechanical stress not only significantly enhanced the mitochondrial HSP60 expression but also induced its partial redistribution to the cytosol. Bioinformatic analyses also confirmed the elevated HSPD1 expression in PAH lungs and PASMCs. HSP60 knockdown effectively attenuated the phenotypic switching of PASMCs induced by hypoxia and mechanical stress.</div></div><div><h3>Conclusion</h3><div>Hypoxia- and mechanical stress-induced upregulation of mitochondrial HSP60 is associated with phenotypic switching of PASMCs.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100089"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564622","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":"Human milk-derived extracellular vesicles promote the heat shock response in polarized microglia","authors":"Jasmyne A. Storm,&nbsp;Jueqin Lu,&nbsp;Mon Francis Obtial,&nbsp;Sanoji Wijenayake","doi":"10.1016/j.cstres.2025.100088","DOIUrl":"10.1016/j.cstres.2025.100088","url":null,"abstract":"<div><div>Milk-derived extracellular vesicles (MEVs) combat acute and chronic pro-inflammation in peripheral cells and tissues. However, the biological functions of MEVs in the central nervous system require exploration. We investigated whether MEVs activate the heat shock response (HSR) in polarized human microglia. MEVs were isolated from unpasteurized human donor milk (n=12 anonymous donors). Human microglia clone 3 cells were primed with 10 ng/mL interferon-gamma to induce polarization, and a subset of cells was supplemented with 200 µg of MEVs. The abundance of HSF1 and candidate heat shock proteins (Hsp70, Hsp90, Hsp40, Hsp27) was analyzed using quantitative reverse transcription polymerase chain reaction and western immunoblotting at 6 h, 12 h, and 24 h post-MEV treatment. We found that MEV treatment promoted the HSR in polarized microglia, compared to homeostatic cells. Furthermore, MEVs increased the duration of the HSR in polarized microglia, exerting robust and continued pro-survival benefits.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100088"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526582","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}