Cell Stress & Chaperones最新文献

{"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, Jia Wang, Peng-Luo Yin, Hua Jia, 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":"2025-06-26","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":"Pathogenic mechanism of the K141E mutation in HSPB8: Insights from smFRET and simulations","authors":"Daniele Montepietra ,&nbsp;Sveinn Bjarnason ,&nbsp;Kristinn R. Óskarsson ,&nbsp;Ciro Cecconi ,&nbsp;Serena Carra ,&nbsp;Pétur O. Heidarsson ,&nbsp;Giorgia Brancolini","doi":"10.1016/j.cstres.2025.100086","DOIUrl":"10.1016/j.cstres.2025.100086","url":null,"abstract":"<div><div>Pathogenic mutations can have a large impact on the conformational ensemble of intrinsically disordered proteins, but revealing those effects and their physiological relevance can be challenging. We used large-scale all-atom explicit-solvent molecular dynamics simulations and single-molecule Förster resonance energy transfer (smFRET) experiments to investigate the conformational dynamics of the chaperone protein HSPB8 and its K141E mutant that is linked to motor neuropathies. Our findings revealed that the HSPB8-K141E mutant exhibits increased conformational flexibility compared to the wild-type protein, particularly at high physiological ionic strengths, leading to a more extended conformational ensemble. Bayesian maximum entropy reweighting was applied to improve agreement between simulated and experimental smFRET data, further emphasizing the mutation’s influence on protein dynamics. While both WT and K141E showed similar primary smFRET peaks after reweighting, the mutant displayed a higher occurrence of a secondary peak at lower FRET, indicative of an unfolded state. Additionally, differences in salt bridge networks between the variants highlighted the role of ionic interactions in modulating protein structure and suggest a possible connection between rapid dynamics and conformational stability. These results suggest that the pathogenicity of the K141E mutation may be, at least in part, due to the enhanced conformational variability that negatively influences the protein function. The study underscores the significance of ionic strength in the structural dynamics of intrinsically disordered proteins like HSPB8, providing insights into the functional implications of these changes and how stability changes can manifest across different timescales.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100086"},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191561","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":"2025-05-25","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":"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":"2025-05-22","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":"2025-05-22","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":"The effect of heat stress on the physiological parameters and blood biomarkers in Malabari goats.","authors":"P Gopikrishnan, Roshin Anie Jose, John Abraham, D K Deepak Mathew, K Raji, N P Sakkariya Ibrahim, P Valavan, T S Nisha, Varun Vijayan","doi":"10.1016/j.cstres.2025.100082","DOIUrl":"https://doi.org/10.1016/j.cstres.2025.100082","url":null,"abstract":"<p><p>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, haematological, biochemical and molecular responses to heat stress in livestock is crucial. The present study was designed to assess the physiological, haematological, biochemical and molecular responses to heat stress in Malabari goat breed, originated in South India. The gene expression patterns of heat shock proteins (HSP) HSP27, HSP70 and HSP90 were also assessed. Twelve adult does were divided into grazing and non-grazing groups and the study was conducted for two months during winter and summer seasons. Higher ambient temperature and solar radiation were recorded in summer with a higher temperature humidity index (THI) 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 theses parameters differed between grazing and non-grazing goats. The pulse rate was significantly influenced by both season and grazing patterns. The haematological parameters like monocyte count, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) in Malabari goats were mainly influenced by seasonal variations. However, the seasonal shift in haematocrit (HCT) levels was not uniform across the grazing strategies. Biochemical parameters, including aspartate aminotransferase (AST) 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 non-grazing goats. HSP70 and HSP90 gene expression increased over the summer, but HSP27 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 heat shock proteins.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"100082"},"PeriodicalIF":3.3,"publicationDate":"2025-05-12","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":"COL5A2-mediated endoplasmic reticulum stress promotes macrophage M2 polarization in lung adenocarcinoma","authors":"Gaozhong Sun ,&nbsp;Yanzhe Wang ,&nbsp;Kewei Ni ,&nbsp;Jian Shen ,&nbsp;Dongdong Liu ,&nbsp;Haitao Wang","doi":"10.1016/j.cstres.2025.100081","DOIUrl":"10.1016/j.cstres.2025.100081","url":null,"abstract":"<div><div>Collagen is a major component of the extracellular matrix. Type V collagen α2 (COL5A2), a common collagen subtype, plays a crucial role in immune regulation, angiogenesis, and tumor metastasis. It is highly expressed in various malignancies, but its mechanistic role in lung adenocarcinoma (LUAD) remains unclear. Therefore, this study aims to investigate the regulatory mechanism of COL5A2 in mediating macrophage M2 polarization in LUAD. We analyzed COL5A2 expression in LUAD samples from the TCGA-LUAD database. Using GSEA, we sought to identify the signaling pathways influenced by COL5A2 expression. mRNA levels of COL5A2, TGF-β, and IL-10 were quantified via qPCR analysis, and protein levels of COL5A2, PD-L1, and endoplasmic reticulum (ER) stress-related proteins (GRP78 and CHOP) were assessed using western blot. Immunofluorescence assay detected the fluorescence signal of CD206 in M2 macrophages, while flow cytometry assessed the M2 macrophage marker CD206, flow cytometry determined the positive rates for CD68 and CD206. Exosome uptake by macrophages was examined using confocal microscopy, and cell viability was measured with cell counting kit-8. KI-67 protein expression was analyzed by immunohistochemistry, and in vivo assays in animals verified our findings. The results showed that elevated COL5A2 levels in LUAD were found to correlate with a shift toward M2 macrophage polarization. Specifically, the overexpression of COL5A2 amplified ER stress, which led to an increase in PD-L1 exosome release and macrophage uptake of PD-L1, thus driving the M2 phenotype. In conclusion, COL5A2 in LUAD induces ER stress, which is associated with elevated PD-L1 exosome secretion and macrophage PD-L1 uptake, ramping up M2 polarization in macrophages.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100081"},"PeriodicalIF":3.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965775","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":"2025-05-06","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":"Editorial Board Members/Copyright","authors":"","doi":"10.1016/S1355-8145(25)00025-2","DOIUrl":"10.1016/S1355-8145(25)00025-2","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Page i"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071185","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":"Cover and caption","authors":"","doi":"10.1016/S1355-8145(25)00024-0","DOIUrl":"10.1016/S1355-8145(25)00024-0","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Page OFC"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071184","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}