Cell Stress & Chaperones最新文献_第8页

Human milk-derived extracellular vesicles promote the heat shock response in polarized microglia 人乳源性细胞外囊泡促进极化小胶质细胞的热休克反应。

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-07-01 Epub Date: 2025-06-26 DOI: 10.1016/j.cstres.2025.100088

Jasmyne A. Storm, Jueqin Lu, Mon Francis Obtial, Sanoji Wijenayake

引用次数: 0

COL5A2-mediated endoplasmic reticulum stress promotes macrophage M2 polarization in lung adenocarcinoma col5a2介导的内质网应激促进肺腺癌中巨噬细胞M2极化。

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-07-01 Epub Date: 2025-05-07 DOI: 10.1016/j.cstres.2025.100081

Gaozhong Sun , Yanzhe Wang , Kewei Ni , Jian Shen , Dongdong Liu , Haitao Wang

{"title":"COL5A2-mediated endoplasmic reticulum stress promotes macrophage M2 polarization in lung adenocarcinoma","authors":"Gaozhong Sun , Yanzhe Wang , Kewei Ni , Jian Shen , Dongdong Liu , 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":"2025-07-01","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}

引用次数: 0

Melatonin ameliorates heat stress-induced oxidative apoptosis in mouse spermatocytes via autophagy and ferroptosis pathways 褪黑素通过自噬和铁下垂途径改善热应激诱导的小鼠精细胞氧化凋亡

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-07-01 Epub Date: 2025-04-20 DOI: 10.1016/j.cstres.2025.100078

Yi-Ping Lei, Jia Wang, Peng-Luo Yin, Hua Jia, Wen-Zhi Ma

{"title":"Melatonin ameliorates heat stress-induced oxidative apoptosis in mouse spermatocytes via autophagy and ferroptosis pathways","authors":"Yi-Ping Lei, Jia Wang, Peng-Luo Yin, Hua Jia, 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":"2025-07-01","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}

引用次数: 0

Pathogenic mechanism of the K141E mutation in HSPB8: Insights from smFRET and simulations HSPB8中K141E突变的致病机制：来自smFRET和模拟的见解。

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-07-01 Epub Date: 2025-05-29 DOI: 10.1016/j.cstres.2025.100086

Daniele Montepietra , Sveinn Bjarnason , Kristinn R. Óskarsson , Ciro Cecconi , Serena Carra , Pétur O. Heidarsson , Giorgia Brancolini

{"title":"Pathogenic mechanism of the K141E mutation in HSPB8: Insights from smFRET and simulations","authors":"Daniele Montepietra , Sveinn Bjarnason , Kristinn R. Óskarsson , Ciro Cecconi , Serena Carra , Pétur O. Heidarsson , 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":"2025-07-01","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}

引用次数: 0

Cover and caption 封面及标题

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-07-01 Epub Date: 2025-07-23 DOI: 10.1016/S1355-8145(25)00042-2

引用次数: 0

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

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-05-01 Epub Date: 2025-05-16 DOI: 10.1016/S1355-8145(25)00025-2

引用次数: 0

Amyloidogenesis promotes HSF1 activity enhancing cell survival during breast cancer metastatic colonization 淀粉样蛋白形成促进HSF1活性，增强乳腺癌转移定殖过程中的细胞存活。

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1016/j.cstres.2025.03.003

Natasha Hockaden , Gabi Leriger , John Wang , Haimanti Ray , Sunandan Chakrabarti , Nicholas Downing , Jacob Desmond , David Williams , Peter C. Hollenhorst , Gregory Longmore , Richard L. Carpenter

{"title":"Amyloidogenesis promotes HSF1 activity enhancing cell survival during breast cancer metastatic colonization","authors":"Natasha Hockaden , Gabi Leriger , John Wang , Haimanti Ray , Sunandan Chakrabarti , Nicholas Downing , Jacob Desmond , David Williams , Peter C. Hollenhorst , Gregory Longmore , 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":"2025-05-01","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}

引用次数: 0

Lycium barbarum polysaccharide alleviates H2O2-induced premature senescence by downregulating miRNA-34a-5p in ARPE-19 cells 枸杞多糖通过下调ARPE-19细胞中的miRNA-34a-5p，缓解H2O2诱导的早衰。

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-05-01 Epub Date: 2025-03-18 DOI: 10.1016/j.cstres.2025.03.002

Meng Kong , Jingwen Li , Rong Jin , Yi Zhang , Jia You , Nan Wang , Nianting Tong

{"title":"Lycium barbarum polysaccharide alleviates H2O2-induced premature senescence by downregulating miRNA-34a-5p in ARPE-19 cells","authors":"Meng Kong , Jingwen Li , Rong Jin , Yi Zhang , Jia You , Nan Wang , 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 H<sub>2</sub>O<sub>2</sub>-induced premature senescence and to elucidate the underlying mechanisms. The ARPE-19 cell line was subjected to H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-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":"2025-05-01","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}

引用次数: 0

Cover and caption 封面及标题

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-05-01 Epub Date: 2025-05-16 DOI: 10.1016/S1355-8145(25)00024-0

引用次数: 0

The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury IRE1α/XBP1信号级联在缺血应激和急性肾损伤自噬中的保护作用

IF 3.3 3区生物学

Cell Stress & Chaperones Pub Date : 2025-05-01 Epub Date: 2025-02-19 DOI: 10.1016/j.cstres.2025.02.004

Ting Liu , Lu Li , Meixia Meng , Ming Gao , Jinhua Zhang , Yuan Zhang , Yukun Gan , Yangjie Dang , Limin Liu

{"title":"The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury","authors":"Ting Liu , Lu Li , Meixia Meng , Ming Gao , Jinhua Zhang , Yuan Zhang , Yukun Gan , Yangjie Dang , Limin Liu","doi":"10.1016/j.cstres.2025.02.004","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}

引用次数: 0