Cell Stress & Chaperones最新文献

{"title":"In memoriam: Leonard M. Neckers (1949–2025)","authors":"Luke Whitesell","doi":"10.1016/j.cstres.2025.100110","DOIUrl":"10.1016/j.cstres.2025.100110","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100110"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925426","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":"Heat shock induces alternative polyadenylation through dynamic DNA methylation and chromatin looping","authors":"Emily E. Fink ,&nbsp;Yi Zhang ,&nbsp;Briana Santo ,&nbsp;Anwita Siddavatam ,&nbsp;Rosie Ou ,&nbsp;Vishal Nanavaty ,&nbsp;Byron H. Lee ,&nbsp;Angela H. Ting","doi":"10.1016/j.cstres.2025.100084","DOIUrl":"10.1016/j.cstres.2025.100084","url":null,"abstract":"<div><div>Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood. Previously, we elucidated a DNA methylation-regulated APA mechanism, in which gene body DNA methylation enhances distal poly(A) isoform expression by blocking CCCTC-binding factor (CTCF) binding and chromatin loop formation at APA control regions. We hypothesized that DNA methylation-regulated APA is one mechanism cells employ to induce proteostasis-promoting poly(A) isoforms. At the <em>DNAJB6</em> cochaperone locus, acute heat shock resulted in binding of stress response transcription factors heat shock factor 1, ATF6, and YY1 at the APA control region and an increase in the expression of the proximal poly(A) isoform known to prevent protein aggregation. Furthermore, TET1 was recruited to rapidly demethylate DNA, facilitating CTCF binding and chromatin loop formation, thereby reinforcing preferential proximal poly(A) isoform expression. As cells recovered, the transcription factors vacated the APA control region, and DNMT1 was recruited to remethylate the region. This process resolved chromatin looping and reset the poly(A) isoform expression pattern. Our findings unveil an epigenetic mechanism enabling cells to dynamically modulate poly(A) isoforms in response to stress while shedding light on the interplay between DNA methylation, transcription factor binding, and chromatin looping.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100084"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141512","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":"Innate extracellular mouse Hsp70 inflammatory properties are mediated by the interaction of Siglec-E and LOX-1 receptors","authors":"Thiago J. Borges ,&nbsp;Karina Lima ,&nbsp;Ayesha Murshid ,&nbsp;Isadora T. Lape ,&nbsp;Maurício M. Rigo ,&nbsp;Benjamin J. Lang ,&nbsp;Thais J. Teani ,&nbsp;Shoib S. Siddiqui ,&nbsp;Leonardo V. Riella ,&nbsp;Cristina Bonorino ,&nbsp;Stuart K. Calderwood","doi":"10.1016/j.cstres.2025.100083","DOIUrl":"10.1016/j.cstres.2025.100083","url":null,"abstract":"<div><div>Innate immune responses to cell damage-associated molecular patterns induce a controlled degree of inflammation, ideally avoiding the promotion of intense unwanted inflammatory adverse events. When released by damaged cells, Hsp70 can stimulate different responses that range from immune activation to immune suppression. The effects of Hsp70 are mediated through innate receptors expressed primarily by myeloid cells, such as dendritic cells (DCs). The regulatory innate receptors that bind to extracellular mouse Hsp70 (mHsp70) are not fully characterized, and neither are their potential interactions with activating innate receptors. Here, we show that extracellular mHsp70 interacts with a receptor complex formed by both inhibitory Siglec-E and activating lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) on DCs. We also find that this interaction takes place in lipid microdomains within the plasma membrane, and that Siglec-E acts as a negative regulator of LOX-1-mediated innate activation upon mHsp70 or oxidized LDL binding. Thus, Hsp70 can both bind to and modulate the interaction of inhibitory and activating innate receptors on the cell surface. These findings add another dimension of regulatory mechanism to indicate how self-molecules contribute to dampening of exacerbated inflammatory responses.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100083"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141453","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":"Corrigendum to “Melatonin ameliorates heat stress-induced oxidative apoptosis in mouse spermatocytes via autophagy and ferroptosis pathways” [Cell Stress Chaperones. 2025;30:100078]","authors":"Yi-Ping Lei,&nbsp;Jia Wang,&nbsp;Peng-Luo Yin,&nbsp;Hua Jia,&nbsp;Wen-Zhi Ma","doi":"10.1016/j.cstres.2025.100087","DOIUrl":"10.1016/j.cstres.2025.100087","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100087"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479993","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":"JNK signaling dominance in hyperthermia","authors":"Atsushi Enomoto ,&nbsp;Takemichi Fukasawa","doi":"10.1016/j.cstres.2025.100080","DOIUrl":"10.1016/j.cstres.2025.100080","url":null,"abstract":"<div><div>Hyperthermia is a promising anticancer treatment that induces heat stress, stimulating various signal transduction pathways to maintain cellular homeostasis. Mitogen-activated protein kinases (MAPKs) link various extracellular stimuli with cytoplasmic and nuclear mediators through a three-tiered cascade of kinases, including MAPKs, MAP2Ks, and MAP3Ks. In mammals, three major groups of MAPKs have been characterized: extracellular signal-regulated protein kinases (ERK), p38 MAPKs, and c-Jun NH₂-terminal kinases (JNK). Each group of MAPKs is heat-activated and exhibits distinct biological functions. However, the differences and advantages of the regulation of each MAPK with temperature changes remain unknown. Our results demonstrated that JNK was activated in a temperature-dependent manner, with degradation of the JNK phosphatases despite transient phosphorylation of ERK with induction of the ERK phosphatases. This brief insight deepens our current understanding of the deregulation of the ERK and JNK cascades in hyperthermia.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100080"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955159","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":"Dynamics of heat shock protein 70 kDa in heat-shocked and hypoxic human endothelial cells","authors":"Luiza B.C.T. Coimbra ,&nbsp;Andrea Pinto-Martinez ,&nbsp;Isadora C.B. Pavan ,&nbsp;Everton G. Melo ,&nbsp;Thaís L.S. Araujo","doi":"10.1016/j.cstres.2025.100085","DOIUrl":"10.1016/j.cstres.2025.100085","url":null,"abstract":"<div><div>Heat shock proteins (HSPs) play crucial roles in human endothelial cell functions such as migration and angiogenesis. However, human HSP dynamics under stress conditions such as heat shock (HS) and hypoxia in human endothelial cells (ECs) are enigmatic, and the characteristics of HSPs in ECs after exposure to thermal stress and a low-oxygen environment are unknown. We hypothesized that ECs adapt to HS and hypoxia by modulating chaperome oligomerization and that HSP70 is a major determinant of the endothelial phenotype. HSP70 inhibition with VER-155008 or YM-1 in primary human endothelial cells decreases EC proliferation, migration, and angiogenesis at baseline and after heat shock recovery. We showed that vascular-independent HSC/P70 multimeric complexes in primary human veins (HUVEC) and coronary artery ECs (HCAEC) accumulate after HS and are decreased by hypoxia. HS recovery increases the number of HSP90 dimers, inducible HSP70, and HSP40 macromolecular complexes, whereas HSC70 returns to baseline. We demonstrated that the HS response and hypoxia regulate HSPs through a new layer of complexity, oligomerization, in addition to classical cochaperone/NEF interactions. The biphasic temporal oligomerization of molecular chaperones in the recovery phase provides a novel face of the heat shock response. In addition, shifts in the subcellular location and upregulation of HSP70 were also observed here. The decrease in HSP expression caused by hypoxia raises the possibility that decreased chaperone power contributes to the endothelial dysfunction found in atherosclerosis, thrombosis, and cancer. Together, these results show that HSP70 is pivotal to the healthy endothelial response in veins and coronary arteries, and we revealed human HSP dynamics in the vascular response to proteotoxic stress.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100085"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157196","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":"HDAC1 is involved in the destabilization of the HSF2 protein under nonstress and stress conditions","authors":"Kevin Daupin ,&nbsp;Véronique Dubreuil ,&nbsp;Johanna K. Ahlskog ,&nbsp;Annalisa Verrico ,&nbsp;Lea Sistonen ,&nbsp;Valérie Mezger ,&nbsp;Aurélie de Thonel","doi":"10.1016/j.cstres.2025.100079","DOIUrl":"10.1016/j.cstres.2025.100079","url":null,"abstract":"<div><div>Heat shock transcription factors 1 and 2 (HSF1 and HSF2) are the major regulators of the cellular response to stressors, notably to heat shock and to oxidative stress. HSF1 and HSF2 are also important contributors in devastating human pathologies like cancer, neurodegenerative disorders, and neurodevelopmental disorders. Under physiological conditions, nuclear HSF2 is detected in only a few cell types in human adult healthy tissues. In contrast, HSF2 protein levels are elevated at some embryonic stages, but greatly vary among cell types and fluctuate during the cell cycle in diverse cell lines. HSF2 is a short-lived protein whose rapid turnover is controlled by the components of the ubiquitin-proteasome degradation pathway, and the stabilization of HSF2 constitutes an important step that regulates its DNA-binding activity and mediates its roles in nonstress, physiological processes. The control of HSF2 abundancy is therefore critical for its regulatory roles in stress responses as well as under physiological conditions. In this regard, the fetal brain cortex is a singular context where HSF2 is strikingly abundant, exhibits constitutive DNA-binding activity and, by controlling a specific repertoire of target genes that play important roles at multiple steps of neurodevelopment. Recently, we showed that the lysine-acetyl-transferases CBP and EP300 stabilize the HSF2 protein under both unstressed and stressed conditions and that the integrity of the CBP/EP300-HSF2 pathway is important for neurodevelopment. Here, we identify the lysine-deacetylase histone-deacetylase 1 (HDAC1) as a novel HSF2-interacting protein partner and regulator, in an unbiased manner, and show that HSF2 and HDAC1 localize in the same cells in the developing mouse cortex and human cerebral organoids. We also demonstrate that HDAC1, through its catalytic activity, destabilizes the HSF2 protein, through HSF2 poly-ubiquitination and proteasomal degradation, under both normal and stress conditions.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100079"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968527","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}