Cell Stress & Chaperones最新文献

英文中文

Amyloidogenesis promotes HSF1 activity enhancing cell survival during breast cancer metastatic colonization

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub 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

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 in vitro 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 in vitro 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.

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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 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub 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

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 Lycium barbarum 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.

背景：视网膜色素上皮（RPE）的过早衰老在老年性黄斑变性的发生中起着重要作用。本研究旨在探讨枸杞多糖（LBP）对H2O2诱导的过早衰老的保护作用，并阐明其潜在机制：方法：将ARPE-19细胞系置于H2O2暴露下，建立早衰模型。方法：ARPE-19 细胞系暴露于 H2O2，以建立早衰模型。模型建立后，细胞在枸杞多糖存在或不存在的情况下维持。使用 antagomir 和 agomir 对 microRNA（miRNA）-34a-5p 的表达进行调节，并通过定量实时聚合酶链反应进行评估：连续三天每天用 200μM H2O2 处理细胞 2 小时，成功建立了衰老模型。这种氧化应激导致衰老相关的 beta-半乳糖苷酶阳性细胞比例明显增加，达到 33.5%，但细胞活力和凋亡没有明显变化。在过早衰老的 ARPE-19 细胞中，活性氧（ROS）生成和丙二醛（MDA）水平明显增加，同时总超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH px）和过氧化氢酶（CAT）的活性显著下降。此外，还发现 miRNA-34a-5p 在这些细胞中过度表达。用枸杞多糖处理可缓解 H2O2 诱导的早衰，减少 miRNA-34a-5p 的过表达，并抑制 ROS 的产生。此外，与 ago-34a 一起孵育可逆转枸杞多糖对 ARPE-19 细胞的保护作用：结论：miRNA-34a-5p的过表达是H2O2诱导ARPE-19细胞早衰的原因之一。枸杞多糖似乎可以通过下调 miRNA-34a-5p 的表达和减少氧化应激来缓解这种过早衰老，至少部分是这样。

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引用次数: 0

Endoplasmic reticulum stress in acute pancreatitis: Exploring the molecular mechanisms and therapeutic targets

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-17 DOI: 10.1016/j.cstres.2025.03.001

Xiaoliang Zhang , Chenchen Xu , LiJuan Ji , Haiwei Zhang

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.

引用次数: 0

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IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-01 DOI: 10.1016/S1355-8145(25)00013-6

引用次数: 0

Editorial Board Members/Copyright

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-01 DOI: 10.1016/S1355-8145(25)00014-8

引用次数: 0

CHOP aggravates hepatocyte apoptosis upon endoplasmic reticulum stress by downregulating autophagy

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-27 DOI: 10.1016/j.cstres.2025.02.005

Jia-Yu Wu , Bing Han , Ting Yang , Lu Zheng , Yi-Xin Guo , Jia-Yao Li , Xiao-Yu Guo , Huan-Huan Yin , Ru-Jia Xie

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.

背景：与内质网（ER）应激相关的细胞凋亡涉及多种肝脏疾病，包括肝纤维化、非酒精性脂肪肝和肝硬化。肝细胞通过引发未折叠蛋白反应（UPR）和增强自噬来应对ER应激。自噬是维持ER正常功能的关键机制，它通过降解受损的ER片段和清除ER腔中的异常蛋白质聚集体来实现。如果不能通过自噬恢复ER平衡，就会对肝细胞造成危害，并导致与ER应激相关的细胞凋亡。最近的研究结果表明，C/EBP同源蛋白（CHOP）可通过下调自噬作用加剧ER应激相关的细胞凋亡，但其潜在机制仍难以确定。目的：研究CHOP对ER应激诱导的大鼠肝细胞凋亡的影响及其潜在的分子机制：方法：用雷帕霉素（RAP）和 3-甲基腺嘌呤预处理 BRL-3A 细胞，然后用二硫苏糖醇（DTT）处理。分别使用实时细胞分析（RTCA）和流式细胞仪检测细胞的生长率和凋亡率。ER应激相关分子水平通过Western印迹法测定。使用 CHOP、小干扰 RNA 和慢病毒载体系统转染 BRL-3A 细胞，观察 CHOP 基因沉默或过表达对自噬和细胞凋亡的影响。染色质免疫共沉淀（ChIP）被用来确认CHOP是否直接与ER应激下的ATG12、ATG5和LC3启动子区域结合：结果：ER应激相关分子在BRL-3A肝细胞中急剧上调，肝细胞凋亡增加。RAP 预处理明显降低了 DTT 诱导的 ER 应激相关分子的表达；相反，3-MA 预处理促进了 DTT 诱导的 ER 应激相关凋亡分子的水平。随着肝细胞中 CHOP 表达的减少，自噬相关分子的水平急剧上升，DTT 诱导的肝细胞凋亡也随之减少。然而，在过表达 CHOP 的细胞中却观察到了相反的趋势。通过 ChIP 检测发现，DTT 处理后，CHOP 对 BRL-3A 细胞中的 ATG12、ATG5 和 LC3 等自噬相关分子有负向调节作用：结论：CHOP在ER应激过程中的增强抑制了自噬，促进了肝细胞凋亡；然而，CHOP基因表达的减少可减轻DTT诱导的肝细胞凋亡。过表达 CHOP 会加重 DTT 诱导的肝细胞凋亡。

引用次数: 0

The Protective Role of the IRE1α/XBP1 Signaling Cascade in Autophagy During Ischemic Stress and Acute Kidney Injury.

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub 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

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 (UPR) pathway, particularly the IRE1α/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 ER 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.

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引用次数: 0

Low serum HSPA12B levels are associated with an increased risk of sarcopenia in a Chinese population of older adults

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-19 DOI: 10.1016/j.cstres.2025.02.003

Xin-Feng Jiao , Yue Gao , Ran Ni , Wen-Ya Zhao , Can Zhao , Xiang Lu , Hai-Feng Zhang , Wei Gao , Lan Luo

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, P < 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, P < 0.001). Moreover, serum HSPA12B concentration was positively correlated with ASMI (r = 0.354, P < 0.001), grip strength (r = 0.381, P < 0.001), and gait speed (r = 0.169, P < 0.001). Multivariate logistic regression analysis showed that decreased serum HSPA12B levels (<185.50 ng/mL) were a risk factor for increased risk of sarcopenia (adjusted odds ratio = 4.335, 95% CI = 3.136–5.993, P < 0.001). In addition, serum HSPA12B level was also positively correlated with serum levels of angiogenesis markers, vascular endothelial growth factor (r = 0.080, P = 0.014), and angiopoietin-1 (r = 0.108, P = 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.

{"title":"Low serum HSPA12B levels are associated with an increased risk of sarcopenia in a Chinese population of older adults","authors":"Xin-Feng Jiao , Yue Gao , Ran Ni , Wen-Ya Zhao , Can Zhao , Xiang Lu , Hai-Feng Zhang , Wei Gao , 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> < 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> < 0.001). Moreover, serum HSPA12B concentration was positively correlated with ASMI (<em>r</em> = 0.354, <em>P</em> < 0.001), grip strength (<em>r</em> = 0.381, <em>P</em> < 0.001), and gait speed (<em>r</em> = 0.169, <em>P</em> < 0.001). Multivariate logistic regression analysis showed that decreased serum HSPA12B levels (<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> < 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}

引用次数: 0

Increased intracellular stress responses and decreased KLF2 in adult patients with atopic dermatitis

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-10 DOI: 10.1016/j.cstres.2025.02.001

Shuji Sugiura , Hiderou Yoshida , Hisashi Sugiura , Masami Uehara , Yasuo Sugiura , Yoshihiro Maruo , Yuji Hayashi , Takefumi Yamamoto , Takeshi Kato , Noriki Fujimoto , Jun Udagawa

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 (HSPA9), heat shock protein 90 beta family member 1 (HSP90B1), calnexin (CANX), malectin (MLEC; endoplasmic reticulum-associated degradation), and heat shock protein family D (Hsp60) member 1 (HSPD1), 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 (KLF2) 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.

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FKBP51 functions in the regulation of circadian rhythm and Alzheimer's disease FKBP51 在调节昼夜节律和阿尔茨海默病中的功能

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-09 DOI: 10.1016/j.cstres.2025.02.002

Jill L. Johnson

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.

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