Cell Stress & Chaperones最新文献

{"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}

{"title":"Editorial Board Members/Copyright","authors":"","doi":"10.1016/S1355-8145(25)00014-8","DOIUrl":"10.1016/S1355-8145(25)00014-8","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 2","pages":"Page i"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628277","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":"CHOP aggravates hepatocyte apoptosis upon endoplasmic reticulum stress by downregulating autophagy","authors":"Jia-Yu Wu ,&nbsp;Bing Han ,&nbsp;Ting Yang ,&nbsp;Lu Zheng ,&nbsp;Yi-Xin Guo ,&nbsp;Jia-Yao Li ,&nbsp;Xiao-Yu Guo ,&nbsp;Huan-Huan Yin ,&nbsp;Ru-Jia Xie","doi":"10.1016/j.cstres.2025.02.005","DOIUrl":"10.1016/j.cstres.2025.02.005","url":null,"abstract":"<div><div>Endoplasmic reticulum (ER) stress-induced apoptosis plays a crucial role in various liver diseases. Hepatocytes respond to ER stress by activating the unfolded protein response and autophagy, which is essential for maintaining ER homeostasis. However, failure to restore ER balance via autophagy contributes to apoptosis. In this study, we aimed to explore the role of C/EBP homologous protein (CHOP) in regulating ER stress-induced apoptosis in rat hepatocytes. We found that CHOP downregulates autophagy, aggravating apoptosis. Our results revealed that inhibition of CHOP expression enhanced autophagy and reduced DTT-induced apoptosis in BRL-3A cells, whereas CHOP overexpression worsened apoptosis. Chromatin immunoprecipitation assays revealed that CHOP negatively regulates autophagy-related genes, such as ATG12, ATG5, and LC3. These findings suggest that CHOP modulation plays a crucial role in ER stress-induced hepatocyte apoptosis by regulating autophagy.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 3","pages":"Pages 109-118"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536593","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":"Low serum HSPA12B levels are associated with an increased risk of sarcopenia in a Chinese population of older adults","authors":"Xin-Feng Jiao ,&nbsp;Yue Gao ,&nbsp;Ran Ni ,&nbsp;Wen-Ya Zhao ,&nbsp;Can Zhao ,&nbsp;Xiang Lu ,&nbsp;Hai-Feng Zhang ,&nbsp;Wei Gao ,&nbsp;Lan Luo","doi":"10.1016/j.cstres.2025.02.003","DOIUrl":"10.1016/j.cstres.2025.02.003","url":null,"abstract":"<div><div>Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass and function. Heat shock protein (HSP) A12B is essential for angiogenesis and endothelial function. However, the association of HSPA12B levels with sarcopenia remains unclear. A total of 936 community-dwelling elderly people were recruited, and serum HSPA12B was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were taken to assess sarcopenia. We found that serum HSPA12B levels in patients with sarcopenia (median [interquartile range] = 182.15 [137.58–225.86] ng/mL) were lower than those in elderly people without sarcopenia (228.96 [193.03–292.93] ng/mL, <em>P</em> &lt; 0.001). Receiver operating characteristic curve analysis indicated that the optimal cut-off value of serum HSPA12B level for predicting sarcopenia was 185.50 ng/mL, with a sensitivity of 52.6% and a specificity of 80.8% (area under curve = 0.742, 95% confidence interval [CI] = 0.711–0.772, <em>P</em> &lt; 0.001). Moreover, serum HSPA12B concentration was positively correlated with ASMI (<em>r</em> = 0.354, <em>P</em> &lt; 0.001), grip strength (<em>r</em> = 0.381, <em>P</em> &lt; 0.001), and gait speed (<em>r</em> = 0.169, <em>P</em> &lt; 0.001). Multivariate logistic regression analysis showed that decreased serum HSPA12B levels (&lt;185.50 ng/mL) were a risk factor for increased risk of sarcopenia (adjusted odds ratio = 4.335, 95% CI = 3.136–5.993, <em>P</em> &lt; 0.001). In addition, serum HSPA12B level was also positively correlated with serum levels of angiogenesis markers, vascular endothelial growth factor (<em>r</em> = 0.080, <em>P</em> = 0.014), and angiopoietin-1 (<em>r</em> = 0.108, <em>P</em> = 0.001). In summary, our results indicate that low serum HSPA12B level is associated with an increased risk of sarcopenia in the elderly, suggesting a potential role of HSPA12B in the development of sarcopenia.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 2","pages":"Pages 100-108"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472192","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":"Increased intracellular stress responses and decreased KLF2 in adult patients with atopic dermatitis","authors":"Shuji Sugiura ,&nbsp;Hiderou Yoshida ,&nbsp;Hisashi Sugiura ,&nbsp;Masami Uehara ,&nbsp;Yasuo Sugiura ,&nbsp;Yoshihiro Maruo ,&nbsp;Yuji Hayashi ,&nbsp;Takefumi Yamamoto ,&nbsp;Takeshi Kato ,&nbsp;Noriki Fujimoto ,&nbsp;Jun Udagawa","doi":"10.1016/j.cstres.2025.02.001","DOIUrl":"10.1016/j.cstres.2025.02.001","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is prone to exacerbations in response to various triggering factors and flare-ups after remission. We searched for molecules associated with relapse/exacerbation of AD among molecules with altered gene expression in the skin of patients with AD. Microarray analyses were performed on lesional and nonlesional skin of adolescent or adult patients with recalcitrant AD and healthy controls. Five chaperones involved in intracellular stress responses, namely heat shock protein family A (Hsp70) member 9 (<em>HSPA9</em>), heat shock protein 90 beta family member 1 (<em>HSP90B1</em>), calnexin (<em>CANX</em>), malectin (<em>MLEC</em>; endoplasmic reticulum-associated degradation), and heat shock protein family D (Hsp60) member 1 (<em>HSPD1</em>), were consistently upregulated in involved and uninvolved skin of patients with AD. Damage-associated molecular patterns were upregulated in involved skin. KLF transcription factor 2 (<em>KLF2</em>) was decreased in involved skin and exhibited a decreasing trend in uninvolved skin of patients with AD. CD4(+)/CD8(+) double-positive cells (1.4% of T cells) were detected in lesions with declined KLF2 levels. WNT inhibitory factor 1 (WIF1) was downregulated in involved skin. Prolactin-induced protein was upregulated in only uninvolved skin of patients with AD. We found increased intracellular stress responses and decreased expression of KLF2 in the skin of patients with AD. Multifactorial genetic diseases, such as asthma, inflammatory bowel disease, type 2 diabetes, and rheumatoid arthritis, are associated with intracellular stress. Intracellular abnormalities may also be responsible for AD. Further research on AD may incorporate enhanced intracellular stress response and the decreased expression of KLF2 into the mechanism underlying AD.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 2","pages":"Pages 84-99"},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406088","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":"FKBP51 functions in the regulation of circadian rhythm and Alzheimer's disease","authors":"Jill L. Johnson","doi":"10.1016/j.cstres.2025.02.002","DOIUrl":"10.1016/j.cstres.2025.02.002","url":null,"abstract":"<div><div>The FK506-binding protein 51 (FKBP51) is an important regulator of glucocorticoid receptor activity and an Hsp90 cochaperone. FKBP51 has previously been identified as a drug target due to its roles in stress-related disorders and pain tolerance. Two recent publications in Cell Stress and Chaperones further explore FKBP51 functions. To understand whether FKBP51 plays a role in sleep disturbances linked to stress disorders, one study examined the role of FKBP51 in regulating the circadian rhythm. Broadening the range of Hsp90 cochaperone function, the other article summarized the role of multiple cochaperones in Alzheimer’s disease, discussing how cochaperones affect both Aβ and tau. They emphasize the role of FKBP51 in promoting tau pathogenesis and discuss the small molecule LA1011, which binds Hsp90 and competes with Hsp90-FKBP51 interaction. Further studies with LA1011 may lead to new treatments for Alzheimer’s disease and will help clarify the contributions of FKBP51 to human disorders.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 2","pages":"Pages 81-83"},"PeriodicalIF":3.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398314","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}