Cell Stress & Chaperones最新文献

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IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-07-01 DOI: 10.1016/S1355-8145(25)00043-4

引用次数: 0

The effect of heat stress on the physiological parameters and blood biomarkers in Malabari goats 热应激对马拉巴里山羊生理参数和血液生物标志物的影响。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-07-01 DOI: 10.1016/j.cstres.2025.100082

Prasannan Gopikrishnan , Roshin Anie Jose , John Abraham , Devasia Kaithakulam Deepak Mathew , Kanakkaparambil Raji , Nalukudy Paramba Sakkariya Ibrahim , Packirisamy Valavan , Thaliyakulam Suresh Nisha , Varun Vijayan

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, hematological, biochemical, and molecular responses to heat stress in livestock is crucial. The present study was designed to assess the physiological, hematological, biochemical, and molecular responses to heat stress in the Malabari goat breed, which originated in South India. The gene expression patterns of heat-shock proteins (HSPs) HSP27, HSP70, and HSP90 were also assessed. Twelve adult does were divided into grazing and nongrazing groups, and the study was conducted for 2 months during winter and summer seasons. Higher ambient temperature and solar radiation were recorded in summer, with a higher temperature-humidity index 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 these parameters differed between grazing and nongrazing goats. The pulse rate was significantly influenced by both season and grazing patterns. The hematological parameters like monocyte count, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration in Malabari goats were mainly influenced by seasonal variations. However, the seasonal shift in hematocrit levels was not uniform across the grazing strategies. Biochemical parameters, including aspartate aminotransferase 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 nongrazing 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 HSPs.

热应激对牲畜健康、生产力和适应能力构成巨大挑战，特别是在热带气候下。在气候变化和全球气温上升的情况下，了解牲畜对热应激的生理、血液学、生化和分子反应至关重要。本研究旨在评估原产于印度南部的马拉巴里山羊品种对热应激的生理、血液学、生化和分子反应。测定热休克蛋白（HSP） HSP27、HSP70和HSP90的基因表达谱。将12只成年公羊分为放牧组和非放牧组，在冬季和夏季进行为期2个月的研究。夏季环境温度和太阳辐射较高，温度湿度指数（THI）较高，表明热应激（77.50±0.27）。山羊呼吸频率、直肠温度和体表温度显著升高，表明动物处于生理应激状态，尤其是在夏季。放牧山羊和非放牧山羊在这些参数的季节变化上存在差异。脉搏率受季节和放牧方式的显著影响。马拉巴利山羊的血液学参数如单核细胞计数、平均红细胞血红蛋白（MCH）、平均红细胞体积（MCV）和平均红细胞血红蛋白浓度（MCHC）主要受季节变化的影响。然而，在不同的放牧策略中，红细胞压积（HCT）水平的季节性变化并不均匀。谷草转氨酶（AST）和丙氨酸转氨酶（ALT）的生化指标表现出显著的季节变化。此外，ALT和总蛋白浓度在放牧组之间存在差异。季节变化对放牧山羊和非放牧山羊葡萄糖浓度的影响有所不同。在我们的研究中，HSP70和HSP90基因的表达在夏季有所增加，但HSP27基因的表达没有表现出任何差异。这些结果表明，作为应激反应机制，马拉巴里山羊在应对热应激时经历了生理、血液学、生化和分子方面的变化，包括重要热休克蛋白的上调。

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引用次数: 0

Hypoxia- and mechanical stress–induced upregulation of mitochondrial HSP60 is associated with phenotypic switching of pulmonary arterial smooth muscle cells 缺氧和机械应力诱导的线粒体HSP60上调与肺动脉平滑肌细胞的表型转换有关。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-07-01 DOI: 10.1016/j.cstres.2025.100089

Geng Liu , Han Nie , Xu Zhang , Zi-Sheng Huang , Koh-Ichiro Yoshiura , Ke-Xiang Liu , Yi Liu , Tao-Sheng Li

Background

Switching from a contractile to a synthetic phenotype of pulmonary arterial smooth muscle cells (PASMCs) is known to play a crucial role in pulmonary arterial hypertension (PAH). We investigated how hypoxia and mechanical stress mediate the phenotypic switching of PASMCs.

Methods

Human PASMCs were used for experiments. Hypoxia treatment was done by culturing cells under 1% O₂. Mechanical stress was induced by loading cells to 50 mmHg hydrostatic pressure. We analyzed cell morphology, cell proliferation, phenotypic marker protein expression, cytokine release, and the activation of stress-related pathways at 24 h after treatment. Bulk and single-cell RNA-sequencing datasets were used to analyze heat shock protein family D member 1 (HSPD1) expression in PAH lungs and PASMCs. Heat shock protein 60 (HSP60) was knocked down in PASMCs by transfection of HSPD1-siRNA.

Results

Either hypoxia or mechanical stress alone induced the morphology change, increased cell proliferation, and promoted the phenotypic switching and inflammatory cytokines release of PASMCs. Interestingly, all those were dramatically enhanced under the combination of hypoxia and mechanical stress. Mechanistically, we found that the combination of hypoxia and mechanical stress not only significantly enhanced the mitochondrial HSP60 expression but also induced its partial redistribution to the cytosol. Bioinformatic analyses also confirmed the elevated HSPD1 expression in PAH lungs and PASMCs. HSP60 knockdown effectively attenuated the phenotypic switching of PASMCs induced by hypoxia and mechanical stress.

Conclusion

Hypoxia- and mechanical stress-induced upregulation of mitochondrial HSP60 is associated with phenotypic switching of PASMCs.

背景：众所周知，肺动脉平滑肌细胞（PASMCs）从收缩型向合成型的转变在肺动脉高压（PAH）中起着至关重要的作用。我们研究了缺氧和机械应力如何介导PASMCs的表型转换。方法：采用人pasmc进行实验。缺氧处理是在1% O₂下培养细胞。将细胞加载至50mmHg静水压力诱导机械应力。我们分析了治疗后24小时的细胞形态、细胞增殖、表型标记蛋白表达、细胞因子释放和应激相关通路的激活。使用大量和单细胞rna测序数据集分析热休克蛋白家族D成员1 （HSPD1）在PAH肺和pasmc中的表达。热休克蛋白60 （HSP60）通过转染HSPD1-siRNA在PASMCs中表达下调。结果：缺氧或机械应力均可诱导PASMCs形态学改变，细胞增殖增加，促进表型转换和炎性细胞因子释放。有趣的是，在缺氧和机械应力的联合作用下，所有这些都显著增强。在机制上，我们发现缺氧和机械应力的结合不仅显著增强了线粒体HSP60的表达，而且诱导其部分重新分布到细胞质中。生物信息学分析也证实了HSPD1在PAH肺和pasmc中的表达升高。HSP60基因敲低可有效减弱缺氧和机械应力诱导的PASMCs表型转换。结论：缺氧和机械应力诱导的线粒体HSP60上调与肺动脉平滑肌细胞的表型转换有关。

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引用次数: 0

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 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-07-01 DOI: 10.1016/j.cstres.2025.100088

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

Milk-derived extracellular vesicles (MEVs) combat acute and chronic pro-inflammation in peripheral cells and tissues. However, the biological functions of MEVs in the central nervous system require exploration. We investigated whether MEVs activate the heat shock response (HSR) in polarized human microglia. MEVs were isolated from unpasteurized human donor milk (n=12 anonymous donors). Human microglia clone 3 cells were primed with 10 ng/mL interferon-gamma to induce polarization, and a subset of cells was supplemented with 200 µg of MEVs. The abundance of HSF1 and candidate heat shock proteins (Hsp70, Hsp90, Hsp40, Hsp27) was analyzed using quantitative reverse transcription polymerase chain reaction and western immunoblotting at 6 h, 12 h, and 24 h post-MEV treatment. We found that MEV treatment promoted the HSR in polarized microglia, compared to homeostatic cells. Furthermore, MEVs increased the duration of the HSR in polarized microglia, exerting robust and continued pro-survival benefits.

乳源性细胞外囊泡（mev）可以对抗周围细胞和组织中的急性和慢性促炎症。然而，mev在中枢神经系统中的生物学功能还有待探索。我们研究了mev是否通过激活热休克反应（HSR）来增强人小胶质细胞对极化的细胞保护。mev从未经巴氏消毒的人供乳中分离出来。人小胶质细胞克隆3 （HMC3）细胞用10 ng/mL IFN-γ诱导极化，一部分细胞补充200µg mev。在mev处理后6h、12h和24h，通过RT-qPCR和western免疫印迹分析HSF1和候选热休克蛋白（Hsp70、Hsp90、Hsp40、Hsp27）的丰度。我们发现，与稳态细胞相比，MEV治疗促进了极化小胶质细胞的HSR。此外，mev增加了极化小胶质细胞HSR的持续时间，发挥了强大和持续的促进生存的益处。

引用次数: 0

Cover and caption 封面及标题

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-07-01 DOI: 10.1016/S1355-8145(25)00042-2

引用次数: 0

Corrigendum to “Melatonin ameliorates heat stress-induced oxidative apoptosis in mouse spermatocytes via autophagy and ferroptosis pathways” [Cell Stress Chaperones. 2025;30:100078] “褪黑素通过自噬和铁凋亡途径改善热应激诱导的小鼠精细胞氧化凋亡”的更正[细胞应激伴侣];2025;30:10 078]

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-06-26 DOI: 10.1016/j.cstres.2025.100087

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

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 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub 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

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.

致病性突变可以对内在无序蛋白质的构象集合产生很大影响，但揭示这些影响及其生理相关性可能具有挑战性。我们使用大规模的全原子显式溶剂分子动力学模拟和单分子共振能量转移（smFRET）实验来研究与运动神经病变相关的伴侣蛋白HSPB8及其K141E突变体的构象动力学。我们的研究结果表明，与野生型蛋白相比，HSPB8-K141E突变体表现出更高的构象灵活性，特别是在高生理离子强度下，导致更广泛的构象集合。采用贝叶斯最大熵重加权来提高模拟和实验smFRET数据的一致性，进一步强调突变对蛋白质动力学的影响。虽然WT和K141E在重新加权后都显示出相似的初级smFRET峰，但突变体在较低的FRET处显示出更高的次级峰，表明未折叠状态。此外，变体之间盐桥网络的差异突出了离子相互作用在调节蛋白质结构中的作用，并表明快速动力学和构象稳定性之间可能存在联系。这些结果表明，K141E突变的致病性可能，至少部分是由于增强的构象变异性，这对蛋白质功能产生了负面影响。该研究强调了离子强度在HSPB8等内在无序蛋白的结构动力学中的重要性，为这些变化的功能含义以及稳定性变化如何在不同时间尺度上表现出来提供了见解。

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引用次数: 0

Dynamics of heat shock protein 70 kDa in heat-shocked and hypoxic human endothelial cells 热休克蛋白70kda在热休克和缺氧人内皮细胞中的动态变化。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-05-25 DOI: 10.1016/j.cstres.2025.100085

Luiza B.C.T. Coimbra , Andrea Pinto-Martinez , Isadora C.B. Pavan , Everton G. Melo , Thaís L.S. Araujo

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.

热休克蛋白（HSPs）在人内皮细胞迁移和血管生成等功能中起着至关重要的作用。然而，人内皮细胞（ECs）在热休克和缺氧等应激条件下的热休克蛋白动力学是谜，内皮细胞在暴露于热应激和低氧环境后的热休克蛋白特征是未知的。我们假设内皮细胞（ECs）通过调节chaperome寡聚化来适应热休克（HS）和缺氧，并且HSP70是内皮表型的主要决定因素。用VER-155008或YM-1抑制原代人内皮细胞的HSP70可降低基线和热休克恢复后EC的增殖、迁移和血管生成。我们发现，在人类初级静脉（HUVECs）和冠状动脉ECs （HCAECs）中，血管独立的HSC/P70多聚体在HS后积累，并因缺氧而减少。热休克恢复使HSP90二聚体、诱导型HSP70和HSP40大分子复合物的数量增加，而HSC70则恢复到基线水平。我们证明，除了经典的cochaperone/NEF相互作用外，热休克反应和缺氧还通过一个新的复杂性层——寡聚化来调节热休克蛋白。在恢复阶段，分子伴侣的双相时间寡聚化提供了热休克反应的新面孔。此外，亚细胞位置的变化和HSP70的上调也在这里被观察到。缺氧引起的HSP表达减少，增加了伴侣蛋白能力降低导致动脉粥样硬化、血栓形成和癌症中内皮功能障碍的可能性。总之，这些结果表明，HSP70对静脉和冠状动脉的健康内皮反应至关重要，我们揭示了人类HSP在血管对蛋白质毒性应激反应中的动态。

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引用次数: 0

Heat shock induces alternative polyadenylation through dynamic DNA methylation and chromatin looping 热休克通过动态DNA甲基化和染色质环诱导选择性聚腺苷化。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-05-22 DOI: 10.1016/j.cstres.2025.100084

Emily E. Fink , Yi Zhang , Briana Santo , Anwita Siddavatam , Rosie Ou , Vishal Nanavaty , Byron H. Lee , Angela H. Ting

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 DNAJB6 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.

选择性切割和聚腺苷酸化（APA）是一种基因调控机制，在应激条件下细胞使用该机制来上调促蛋白酶转录物，但细胞如何实现这一目标仍然知之甚少。此前，我们阐明了DNA甲基化调控的APA机制，其中基因体DNA甲基化通过阻断CTCF结合和APA控制区染色质环的形成来增强远端poly(a)异构体的表达。我们假设DNA甲基化调控的APA是细胞诱导促进蛋白稳定的聚(A)亚型的一种机制。在DNAJB6共伴侣位点，急性热休克导致应激反应转录因子HSF1、ATF6和YY1在APA控制区结合，并增加了已知可阻止蛋白质聚集的近端聚(A)异构体的表达。此外，TET1被招募来快速去甲基化DNA，促进CTCF结合和染色质环的形成，从而加强近端聚(A)异构体的优先表达。随着细胞恢复，转录因子清空APA控制区，DNMT1被招募到该区域进行再甲基化。这个过程解决了染色质环并重置了poly(A)异构体表达模式。我们的发现揭示了一种表观遗传机制，使细胞能够动态调节poly(A)亚型以响应应激，同时揭示了DNA甲基化，转录因子结合和染色质环之间的相互作用。

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引用次数: 0

Innate extracellular mouse Hsp70 inflammatory properties are mediated by the interaction of Siglec-E and LOX-1 receptors 先天细胞外小鼠Hsp70炎症特性是由siglece和LOX-1受体的相互作用介导的。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-05-22 DOI: 10.1016/j.cstres.2025.100083

Thiago J. Borges , Karina Lima , Ayesha Murshid , Isadora T. Lape , Maurício M. Rigo , Benjamin J. Lang , Thais J. Teani , Shoib S. Siddiqui , Leonardo V. Riella , Cristina Bonorino , Stuart K. Calderwood

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.

先天免疫应答细胞损伤相关的分子模式诱导炎症的控制程度，理想地避免促进强烈的不想要的炎症不良事件。当受损细胞释放Hsp70时，可以刺激从免疫激活到免疫抑制的不同反应。Hsp70的作用是通过主要由髓细胞（如树突状细胞）表达的先天受体介导的。结合细胞外小鼠Hsp70 （mHsp70）的调节先天受体尚未完全表征，它们与激活先天受体的潜在相互作用也尚未完全确定。在这里，我们发现细胞外mHsp70与抑制siglece和激活dc上的LOX-1形成的受体复合物相互作用。我们还发现这种相互作用发生在质膜内的脂质微域，并且siglece作为lox -1介导的mHsp70先天激活或氧化LDL结合的负调节因子。因此，Hsp70可以结合并调节细胞表面抑制和激活先天受体的相互作用。这些发现增加了调节机制的另一个维度，表明自我分子如何有助于抑制加剧的炎症反应。

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