Cell Stress & Chaperones最新文献

{"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}

{"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":"2025-05-01","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":"The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury","authors":"Ting Liu ,&nbsp;Lu Li ,&nbsp;Meixia Meng ,&nbsp;Ming Gao ,&nbsp;Jinhua Zhang ,&nbsp;Yuan Zhang ,&nbsp;Yukun Gan ,&nbsp;Yangjie Dang ,&nbsp;Limin Liu","doi":"10.1016/j.cstres.2025.02.004","DOIUrl":"10.1016/j.cstres.2025.02.004","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a common and serious complication resulting from ischemia and hypoxia, leading to significant morbidity and mortality. Autophagy, a cellular process for degrading damaged components, plays a crucial role in kidney protection. The unfolded protein response pathway, particularly the inositol-requiring enzyme 1 (IRE1α)/X-box binding protein 1 (XBP1) signaling cascade, is implicated in regulating autophagy during renal stress. To elucidate the role of the IRE1α/XBP1 pathway in autophagy during hypoxia/reoxygenation (H/R) and ischemia/reperfusion (I/R) injury, renal tubular epithelial cells (TECs) were subjected to H/R conditions, and I/R injury was induced in mice. The expression of autophagy-related and endoplasmic reticulum stress markers (IRE1α, XBP1, GRP78, Beclin1, LC3I/II, and P62) was assessed using immunoblotting and immunofluorescence. Additionally, the impacts of IRE1α overexpression and pharmacological agents, IXA6 (IRE1α agonist), and STF083010 (IRE1α inhibitor) were evaluated on autophagy regulation. H/R injury significantly increased mitochondrial damage and the formation of autophagic vesicles in TECs. Key markers of autophagy were elevated in response to H/R and I/R injury, with activation of the IRE1α/XBP1 pathway enhancing autophagic processes. IXA6 treatment improved renal function and reduced injury in I/R models, while STF083010 exacerbated kidney damage. The IRE1α/XBP1 pathway is a critical regulator of autophagy in renal TECs during ischemic stress, suggesting that pharmacological modulation of this pathway may offer therapeutic avenues for preventing or mitigating AKI. Enhanced understanding of these mechanisms may lead to novel strategies for kidney disease management.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Pages 160-171"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472193","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":"Melatonin ameliorates heat stress-induced oxidative apoptosis in mouse spermatocytes via autophagy and ferroptosis pathways","authors":"Yi-Ping Lei,&nbsp;Jia Wang,&nbsp;Peng-Luo Yin,&nbsp;Hua Jia,&nbsp;Wen-Zhi Ma","doi":"10.1016/j.cstres.2025.100078","DOIUrl":"10.1016/j.cstres.2025.100078","url":null,"abstract":"<div><div>Testicular heat stress is a critical factor contributing to male infertility, with spermatocytes exhibiting heightened sensitivity to temperature elevation. This study systematically elucidates the protective mechanisms of melatonin against heat stress-induced spermatocyte injury. In a murine heat stress model, melatonin intervention significantly reduced testicular accumulation of malondialdehyde (MDA) induced by heat stress, enhanced the activities of catalase (CAT) and superoxide dismutase (SOD), and suppressed germ cell apoptosis by downregulating the pro-apoptotic protein Bax and upregulating GPX4 expression. Sycp3 immunohistochemistry demonstrated that melatonin significantly improved spermatocyte structural integrity. In the GC-2spd (ts) spermatocyte cell line model, melatonin treatment markedly reduced MDA levels and alleviated heat stress-induced oxidative apoptosis and proliferation inhibition by downregulating key apoptotic proteins (Bax, Caspase-3, and cleaved-Caspase-3). Mechanistic studies revealed that melatonin restores autophagic balance by modulating the expression of autophagy-related proteins LC3-I, LC3-II, and P62. Concurrently, melatonin downregulated ferroptosis markers P53 and COX2, inhibiting ferroptosis by blocking DNA damage response and inflammatory amplification pathways. Melatonin synergistically maintained cellular redox homeostasis by downregulating the NRF2/HO-1 pathway and upregulating GPX4 expression, significantly reducing Fe²⁺ accumulation and ameliorating iron metabolism dysregulation. This study unveils the molecular mechanisms by which melatonin mitigates testicular heat stress injury through a multitarget regulatory network, providing novel therapeutic strategies for clinical intervention in heat stress-associated infertility.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100078"},"PeriodicalIF":3.3,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922054","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":"Amyloidogenesis promotes HSF1 activity enhancing cell survival during breast cancer metastatic colonization","authors":"Natasha Hockaden ,&nbsp;Gabi Leriger ,&nbsp;John Wang ,&nbsp;Haimanti Ray ,&nbsp;Sunandan Chakrabarti ,&nbsp;Nicholas Downing ,&nbsp;Jacob Desmond ,&nbsp;David Williams ,&nbsp;Peter C. Hollenhorst ,&nbsp;Gregory Longmore ,&nbsp;Richard L. Carpenter","doi":"10.1016/j.cstres.2025.03.003","DOIUrl":"10.1016/j.cstres.2025.03.003","url":null,"abstract":"<div><div>Breast cancer is the most commonly diagnosed cancer among women and the second leading cause of cancer deaths in women. A majority of these breast cancer deaths are due to metastasis, which occurs when primary tumor cells invade into the blood stream to travel and colonize at distant organ sites. Metastatic colonization is the rate-limiting step of metastasis. Heat shock factor 1 (HSF1) is a transcription factor that has been shown to be involved in promoting malignancy with a function in metastatic dissemination due to its contribution to promoting epithelial-to-mesenchymal transition. The role of HSF1 in colonization is unclear. In this study, we observed that HSF1 was essential for metastatic colonization. Consistent with these findings, we also observed that HSF1 was more active in human metastatic tumors compared to primary tumors. HSF1 was also seen to be activated during <em>in vitro</em> colony formation, which was accompanied by increases in amyloid beta (Aβ) fibrils, which was also observed in human metastatic tumors. Aβ fibrils led to HSF1 activation and depletion or inhibition of HSF1 led to increases in Aβ fibrils. HSF1 inhibition with small molecule inhibitors suppressed <em>in vitro</em> colony formation and mammosphere growth of metastatic breast cancer cells. These results suggest that colonization increases Aβ fibril formation that subsequently activates HSF1 as a cell survival mechanism that is essential for metastatic initiation and outgrowth.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Pages 143-159"},"PeriodicalIF":3.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728855","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":"Lycium barbarum polysaccharide alleviates H2O2-induced premature senescence by downregulating miRNA-34a-5p in ARPE-19 cells","authors":"Meng Kong ,&nbsp;Jingwen Li ,&nbsp;Rong Jin ,&nbsp;Yi Zhang ,&nbsp;Jia You ,&nbsp;Nan Wang ,&nbsp;Nianting Tong","doi":"10.1016/j.cstres.2025.03.002","DOIUrl":"10.1016/j.cstres.2025.03.002","url":null,"abstract":"<div><div>The premature senescence of retinal pigment epithelium (RPE) plays a significant role in the development of age-related macular degeneration. This study aimed to investigate the potential protective effect of <em>Lycium barbarum</em> polysaccharide (LBP) against H₂O₂-induced premature senescence and to elucidate the underlying mechanisms. The ARPE-19 cell line was subjected to H₂O₂ exposure to create a model of premature senescence. The modulation of microRNA-34a-5p expression was accomplished using antagomir and agomir, as assessed by quantitative real-time polymerase chain reaction. The senescence model was successfully established by treating cells with 200 μM H₂O₂ for 2 hours daily over a span of three consecutive days. This oxidative stress resulted in a notable increase in the proportion of senescence-associated beta-galactosidase-positive cells, reaching 33.5%, without significant alterations in cell viability or apoptosis. In the ARPE-19 cells undergoing premature senescence, there was a marked increase in reactive oxygen species (ROS) production and malondialdehyde levels, coupled with a significant decrease in the activity of total superoxide dismutase, glutathione peroxidase, and catalase. Additionally, microRNA-34a-5p was found to be overexpressed in these cells. Treatment with LBP alleviated H₂O₂-induced premature senescence, diminished the overexpression of microRNA-34a-5p, and suppressed ROS production. Moreover, the incubation with ago-34a reversed the protective effect of LBP in ARPE-19 cells. In conclusion, the overexpression of microRNA-34a-5p contributes to the H₂O₂-induced premature senescence of ARPE-19 cells. LBP appears to mitigate this premature senescence, at least in part, by downregulating microRNA-34a-5p expression and reducing oxidative stress.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Pages 130-142"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669223","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":"Endoplasmic reticulum stress in acute pancreatitis: Exploring the molecular mechanisms and therapeutic targets","authors":"Xiaoliang Zhang ,&nbsp;Chenchen Xu ,&nbsp;LiJuan Ji ,&nbsp;Haiwei Zhang","doi":"10.1016/j.cstres.2025.03.001","DOIUrl":"10.1016/j.cstres.2025.03.001","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is associated with multiple cellular mechanisms that trigger and or are triggered by the inflammatory injury and death of the acinar cells. One of the key mechanisms is the endoplasmic reticulum (ER) stress, which manifests as an accumulation of misfolded proteins within ER, an event that has proinflammatory and proapoptotic consequences. Hence, the degree of cell insult during AP could considerably depend on the signaling pathways that are upregulated during ER stress and its resulting dyshomeostasis such as C/EBP homologous protein (CHOP), cJUN NH2-terminal kinase (JNK), nuclear factor kappa B (NF-κB), and NOD-like receptor protein 3 (NLRP3) inflammasome. Exploring these molecular pathways is an interesting area for translational medicine as it may lead to identifying new therapeutic targets in AP. This review of the literature aims to shed light on the different roles of ER stress in the etiopathogenesis and pathogenesis of AP. Then, it specifically focuses on the therapeutic implications of ER stress in this context.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Pages 119-129"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662307","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":"Cover and caption","authors":"","doi":"10.1016/S1355-8145(25)00013-6","DOIUrl":"10.1016/S1355-8145(25)00013-6","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 2","pages":"Page OFC"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628276","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}