Cell Stress & Chaperones最新文献

英文中文

Molecular response of canine testis to GnRH agonist: Insights into AR, HIF-1α, and HSPs expression during arrest and recovery of spermatogenesis 犬睾丸对GnRH激动剂的分子反应：在精子发生停止和恢复过程中对AR、HIF-1α和HSPs表达的见解

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-01 DOI: 10.1016/j.cstres.2024.11.007

Anastasiia Vasetska , Eva-Maria Packeiser , Hanna Körber , Selim Aslan , Serhan Ay , Murat Findik , Firdevs Binli , Murat Selçuk , Christelle Speiser-Fontaine , Sandra Goericke-Pesch

Slow-release gonadotropin-releasing hormone (GnRH) agonist implants are frequently used for contraception in male dogs. Although the effects are fully reversible, there is still concern about the safety of the implant’s mode of action. Addressing this, we investigated cellular stress and androgen receptor (AR) signaling during downregulation and recovery. Testicular tissues were sampled from dogs castrated at different time points after GnRH implant removal and compared with untreated controls. AR, hypoxia-inducible factor 1 (HIF1A), heat shock proteins heat shock protein 72 (HSP72), heat shock protein 73 (heat shock cognate, HSPA8) (HSP73), heat shock protein A2 (HSPA2), heat shock protein 90 alpha (inducible isoform) (HSP90AA1), and heat shock protein 90 beta (constitutive isoform) (HSP90AB1) were investigated by quantitative real-time polymerase chain reaction and AR, HSP72, HSP73, and HSP90 immunohistochemically. While AR, HIF1A, and HSP70 were upregulated at gene expression level, HSPA8, HSPA2, and HSP90AA1 expression were downregulated during spermatogenic arrest; HSP90AB1 expression did not change. Immunohistochemistry verified AR-expression in Sertoli, peritubular, and Leydig cells, occasionally also in spermatogonia. Stress-inducible HSP72 was occasionally detected, while constitutive HSP73 and HSP90 were abundantly expressed by germ cells. Our results were similar to studies on seasonal breeders such as pine voles, geese, fish, and soft-shelled turtles. Accordingly, GnRH implants did not impose additional cellular stress on testicular cells when compared with natural recrudescence. Since comparative data on HIF1α are scarce, we cannot draw conclusions about hypoxic conditions.

缓慢释放的促性腺激素释放激素（GnRH）激动剂植入物经常用于雄性犬的避孕。虽然这些影响是完全可逆的，但人们仍然担心植入物的作用方式的安全性。为了解决这个问题，我们研究了下调和恢复过程中的细胞应激和雄激素受体信号。从GnRH植入物移除后不同时间点去势的狗的睾丸组织中取样，并与未处理的对照组进行比较。采用qPCR方法检测雄激素受体（AR）、缺氧诱导因子1 （HIF1A）和热休克蛋白HSP72、HSP73、HSPA2、HSP90AA1和HSP90AB1，并用免疫组织化学方法检测AR、HSP72、HSP73和HSP90。AR、HIF1A和HSP70 mRNA水平上调，HSPA8、HSPA2和HSP90AA1 mRNA水平下调；HSP90AB1表达无明显变化。免疫组织化学证实ar在支持细胞、小管周围细胞和间质细胞中表达，偶尔也在精原细胞中表达。胁迫诱导型HSP72偶有检测到，而组成型HSP73和HSP90在生殖细胞中大量表达。我们的研究结果与松田鼠、鹅、鱼和鳖等季节性繁殖动物的研究结果相似。因此，与自然复发相比，GnRH植入物不会对睾丸细胞施加额外的细胞应激。由于HIF1α的比较数据缺乏，我们无法得出关于缺氧条件的结论。

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引用次数: 0

Secreted extracellular heat shock protein gp96 and inflammatory cytokines are markers of severe malaria outcome 分泌的细胞外热休克蛋白gp96和炎症细胞因子是严重疟疾结局的标志。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-01 DOI: 10.1016/j.cstres.2024.12.004

Fatou Thiam , Djibaba Djoumoi , Mame Ndew Mbaye , Aminata Fall , Abou Abdallah Malick Diouara , Mamadou Diop , Cheikh Momar Nguer , Babacar Mbengue , Gora Diop , Evelyne Kohli , Alioune Dieye

Malaria caused by Plasmodium spp., is a major public health issue in sub-Saharan Africa. The fight against malaria has stalled due to increasing resistance to treatments and insecticides. There is an urgent need to focus on new therapeutic targets to combat malaria effectively. This study aimed to measure the secreted heat shock protein gp96 levels in both malaria patients and controls. Indeed, gp96 plays a crucial role in parasite survival within the host and in establishing a successful infection. Therefore, gp96 could be a promising target for antimalarial drugs. In our study, we included 60 malaria patients, 30 with severe malaria (SM) and 30 with uncomplicated malaria (UM). Additionally, 28 controls were included. Using the ELISA method, we measured gp96 levels in the participants' blood samples. We then used the Mann–Whitney or analyse of variance tests to calculate descriptive statistics and determined the correlation between gp96 level and parasitemia using Spearman's rank correlation test. The study found that gp96 levels in the plasma significantly increased in malaria patients (23.86 ng/mL) compared to control (5.88 ng/mL), with a P < 0.0001. Interestingly, there was a significant difference between SM (27.56 ng/mL) and UM (13.9 ng/mL), with a P-value of 0.001. These findings are accompanied by significantly higher parasitemia and elevated proinflammatory cytokines such as IL-17A and IL-1β levels in SM patients compared to UM and controls. Furthermore, there was no significant positive correlation between gp96 levels and parasitemia/proinflammatory cytokines. Our research has revealed, for the first time, that individuals with SM have significantly higher levels of gp96 in the context of high parasitemia and proinflammatory cytokines. Our preliminary results will be taken further to evaluate gp96 as a valuable biomarker for the diagnosis of SM and a potential target for antimalarial drug discovery.

由疟原虫引起的疟疾是撒哈拉以南非洲的一个主要公共卫生问题。由于对治疗和杀虫剂的耐药性日益增强，防治疟疾的斗争陷入停滞。迫切需要关注新的治疗靶点，以有效地防治疟疾。本研究旨在测量疟疾患者和对照组中分泌的热休克蛋白gp96水平。事实上，gp96在寄生虫在宿主内的生存和成功感染中起着至关重要的作用。因此，gp96可能是抗疟疾药物的一个有希望的靶点。在我们的研究中，我们纳入了60例疟疾患者，其中30例为重度疟疾（SM）， 30例为非复杂性疟疾（UM）。此外，还纳入了28例对照（CTR）。采用ELISA法测定了受试者血样中的gp96水平。然后，我们使用Mann-Whitney检验或ANOVA检验计算描述性统计量，并使用Spearman秩相关检验确定gp96水平与寄生虫病之间的相关性。研究发现，与对照组（5.88ng/mL）相比，疟疾患者血浆中gp96水平（23.86ng/mL）显著升高，p < 0.0001。有趣的是，SM （27.56ng/mL）和UM （13.9ng/mL）之间存在显著差异，p值为0.001。与UM和对照组相比，这些发现伴随着SM患者明显更高的寄生虫血症和升高的促炎细胞因子如IL-17A和IL-1β水平。此外，gp96水平与寄生虫血症/促炎细胞因子之间无显著正相关。我们的研究首次揭示，在高寄生虫血症和促炎细胞因子的背景下，严重疟疾患者的gp96水平明显较高。我们的初步结果将进一步评估gp96作为诊断严重疟疾的有价值的生物标志物和抗疟疾药物发现的潜在靶点。

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引用次数: 0

Large-scale energy decomposition for the analysis of protein stability

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-01 DOI: 10.1016/j.cstres.2025.01.001

Samman Mansoor , Elena Frasnetti , Ivan Cucchi , Andrea Magni , Giorgio Bonollo , Stefano A. Serapian , Luca F. Pavarino , Giorgio Colombo

To carry out their functions in cells, proteins are required to fold into well-defined three-dimensional conformations. The stability of the folded state dictates several aspects of protein life, such as their evolution, interactions, and selection of structures that are ultimately linked to activity. Sequence mutations may change the stability profile and consequently impact structure and function. Here, we use a simple, molecular dynamics-based energy decomposition approach to map the response to mutations of each amino acid in the sequences of a set of five test proteins with different lengths, folds, and topologies. To this end, we make use of the decomposition of the residue-pair nonbonded energy matrix. We show that parameters obtained from this analysis, namely the main eigenvalue reporting on the most stabilizing energy contributions and the spectral gap of the matrix (ENergy Gap), reproduce experimentally determined stability trends. At the same time, our approach identifies the residue-pair couplings that play key roles in defining the 3D properties of a certain fold. We discuss the relevance of these results for the design of protein mutants for experimental applications and the possibility for our energy decomposition approach to complement other computational and experimental analyses of conformational stability.

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引用次数: 0

HSP mRNA sequences and their expression under different thermal oscillation patterns and heat stress in two populations of Nodipecten subnodosus 不同热振荡模式和热胁迫下两个种群的HSP mRNA序列及其表达。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-01 DOI: 10.1016/j.cstres.2024.12.002

Axel Bonesteve , Salvador E. Lluch-Cota , Maria Teresa Sicard , Ilie S. Racotta , Miguel A. Tripp-Valdez , Liliana Rojo-Arreola

Understanding the molecular mechanisms underlying thermal acclimation and heat shock responses in marine ectotherms is critical for assessing their adaptive capacity in the context of climate change and climate extremes. This study examines the expression dynamics of heat shock proteins (HSPs) in the scallop Nodipecten subnodosus, shedding light on their role in thermal adaptation. Our analysis revealed the presence of several conserved functional signatures in N. subnodosus HSPs deduced amino acid sequences. Comparative gene expression profiling between two populations of N. subnodosus, maintained for 15 days under constant and oscillatory thermal regimes and then exposed to acute heat stress, revealed conserved adaptive traits. The heat-inducible nature of N. subnodosus HSP70 (HSPA8) gene expression highlights its potential as a stress marker, in contrast to its human homolog, which is constitutively expressed. Furthermore, the identification of HSP90 (HSPC3) and its overexpression during acute heat stress underscores its critical role in initiating a protective stress response. Population-specific responses in the magnitude of gene expression were observed; however, both populations exhibited similar overall patterns of HSP induction, suggesting a shared adaptive response mechanism. This study also elucidated the diversity and expansion of members of the HSP70 family members, specifically the HSPA12 subfamily, in N. subnodosus. This characteristic, previously observed in other bivalves, underscores the role of HSPA12 in environmental adaptation, providing molecular plasticity to withstand varying environmental pressures. These findings offer valuable insights into the molecular basis of thermal adaptation in N. subnodosus, highlighting the importance of HSPs in coping with environmental stochasticity under climate change scenarios.

了解海洋变温动物热适应和热休克反应（HSR）的分子机制对于评估其在气候变化和极端气候背景下的适应能力至关重要。本研究研究了热休克蛋白（HSPs）在扇贝Nodipecten subnodosus中的表达动态，揭示了它们在热适应中的作用。我们的分析揭示了N. subnodosus热休克蛋白的氨基酸序列中存在几个保守的功能特征。在恒定和振荡热环境下维持15天，然后暴露于急性热应激下，两个亚结节棘豆种群的基因表达谱比较揭示了保守的适应特征。N. subnodosus HSP70 （HSPA8）基因表达的热诱导性质突出了其作为应激标记物的潜力，与其人类同源物相比，后者是组成性表达的。此外，HSP90 （hsp3）的鉴定及其在急性热应激中的过表达强调了它在启动保护性应激反应中的关键作用。观察到基因表达量的群体特异性反应；然而，这两个种群表现出相似的热休克诱导总体模式，表明具有共同的适应反应机制。本研究还阐明了HSP70家族成员（特别是HSPA12亚家族）在N. subnodosus中的多样性和扩展。这一特性，之前在其他双壳类动物中观察到，强调了HSPA12在环境适应中的作用，提供分子可塑性以承受不同的环境压力。这些发现为研究亚结节棘藓热适应的分子基础提供了有价值的见解，强调了热敏感蛋白在气候变化情景下应对环境随机性的重要性。

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引用次数: 0

Ceapin-A7 suppresses the protective effects of Octreotide in human and bovine lung endothelial cells Ceapin-A7抑制奥曲肽对人和牛肺内皮细胞的保护作用。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-01 DOI: 10.1016/j.cstres.2024.12.001

Saikat Fakir, Madan Sigdel, Md Matiur Rahman Sarker, Joy T. Folahan, Nektarios Barabutis

Endothelial injury can be the cause and consequence of severe inflammation and injury. Synthetic somatostatin analogs—which suppress Growth Hormone—are clinically-approved drugs associated with anti-inflammatory activities. In the present study, we suggest that the protective activities of Octreotide in human and bovine endothelial cells are mitigated by Ceapin-A7, which is an activating transcription factor 6 inhibitor. To study endothelial function, we assessed protein expression levels of key cytoskeletal proteins, as well as paracellular permeability. To evaluate inflammation, we measured factors that promote vascular leak, as well as reactive oxygen species generation. Collectively, our study supports the involvement of activating transcription factor 6 in the protective effects of Octreotide in endothelial barrier function.

内皮损伤可能是严重炎症和损伤的原因和后果。合成的生长抑素类似物——抑制生长激素——是fda批准的具有抗炎活性的药物。在本研究中，我们认为奥曲肽对人和牛内皮细胞的保护作用被Ceapin-A7（一种激活转录因子6的抑制因子）所减弱。为了研究内皮功能，我们评估了关键细胞骨架蛋白的蛋白表达水平以及细胞旁通透性。为了评估炎症，我们测量了促进血管泄漏的因素，以及活性氧的产生。总的来说，我们的研究支持激活转录因子6参与奥曲肽对内皮屏障功能的保护作用。

引用次数: 0

FKBP51 overexpression in the corticolimbic system stabilizes circadian rhythms 皮质边缘系统中 FKBP51 的过度表达可稳定昼夜节律

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-01 DOI: 10.1016/j.cstres.2024.12.003

Niat T. Gebru , David Beaulieu-Abdelahad , Danielle Gulick , Laura J. Blair

Circadian rhythm disruptions have been associated with a wide range of health issues and complications, including an increased risk of circadian rhythm sleep disorders (CRSDs). CRSDs are common among individuals who have been through a traumatic event, particularly in those who have post-traumatic stress disorder (PTSD). Allelic variations in the gene encoding for FK506-binding protein 51 (FKBP51) can increase the susceptibility for PTSD and other stress-related disorders following trauma. At least one of these variants increases the levels of FKBP51 following stress through a glucocorticoid receptor-mediated process. Here, we used a mouse model that overexpresses human FKBP51 throughout the forebrain, rTgFKBP5, to investigate if elevated FKBP51 contributes to circadian rhythm disruption. Surprisingly, our findings indicate a greater rhythm amplitude and decreased rhythm fragmentation in rTgFKBP5 mice, particularly females, compared to controls. Female rTgFKBP5 mice also showed higher corticosterone levels basally and following stress exposure. Overall, this study associates FKBP51 overexpression with beneficial circadian rhythm outcomes.

昼夜节律紊乱与广泛的健康问题和并发症有关，包括昼夜节律睡眠障碍（crsd）的风险增加。crsd在经历过创伤性事件的个体中很常见，特别是在那些患有创伤后应激障碍（PTSD）的个体中。编码fk506结合蛋白51 （FKBP51）基因的等位基因变异可增加创伤后应激障碍和其他应激相关疾病的易感性。这些变体中至少有一种通过糖皮质激素受体介导的过程增加应激后FKBP51的水平。在这里，我们使用了一个在整个前脑过度表达人类FKBP51的小鼠模型，rTgFKBP5，来研究FKBP51的升高是否会导致昼夜节律紊乱。令人惊讶的是，我们的研究结果表明，与对照组相比，rTgFKBP5小鼠（尤其是雌性）的节律幅度更大，节律碎片化程度更低。雌性rTgFKBP5小鼠在应激暴露基础上和应激暴露后也表现出更高的皮质酮水平。总的来说，本研究将FKBP51过表达与有益的昼夜节律结果联系起来。

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引用次数: 0

Hsp90: Bringing It All Together.

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-01-29 DOI: 10.1016/j.cstres.2025.01.002

Georgios Ioannis Karras, Giorgio Colombo, Andrea N Kravats

Heat-shock protein 90 (Hsp90) is an ancient and multifaceted protein-folding machine essential for most organisms. The past 40 years have uncovered remarkable complexity in the regulation and function of Hsp90, which dwarfs in sophistication most other machines in the cell. Here, we propose four analogies to illustrate Hsp90's sophistication: a multifunctional Swiss Army knife, an automobile engine and its controls, a switchboard acting as a hub and directing signals, and an orchestra conductor setting the tempo of a symphony. Although each of these analogies represents some key Hsp90 activities, none of them captures the entirety of Hsp90's complexity. Together, these roles enable Hsp90 to support both homeostasis and differentiation, both cellular stability and adaptability. At the 11th International Conference on the Hsp90 Chaperone Machine, the consensus was that to understand this major guardian of proteostasis, we need to study how the many facets of Hsp90's function influence each other. We hope that these analogies will help to conceptually integrate the many roles of Hsp90 in proteostasis and help the field develop the practical applications of Hsp90 modulators.

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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 : 2024-12-01 DOI: 10.1016/S1355-8145(24)00137-8

引用次数: 0

Cover and caption

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2024-12-01 DOI: 10.1016/S1355-8145(24)00136-6

引用次数: 0

Endoplasmic reticulum stress-mediated apoptosis and autophagy in osteoarthritis: From molecular mechanisms to therapeutic applications 骨关节炎中内质网应激介导的细胞凋亡和自噬：从分子机制到治疗应用。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2024-12-01 DOI: 10.1016/j.cstres.2024.11.005

Yifan Lu , Jing Zhou , Hong Wang , Hua Gao , Eryu Ning , Zhiqiang Shao , Yuefeng Hao , Xing Yang

Osteoarthritis (OA) is characterized primarily by the degeneration of articular cartilage, with a high prevalence and disability rate. The functional phenotype of chondrocytes, as the sole cell type within cartilage, is vital for OA progression. Due to the avascular nature of cartilage and its limited regenerative capacity, repair following injury poses significant challenges. Various cellular stressors, including hypoxia, nutrient deprivation, oxidative stress, and collagen mutations, can lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), resulting in ER stress (ERS). In response to restore ER homeostasis as well as cellular vitality and function, a series of adaptive mechanisms are triggered, including the unfolded protein response, ER-associated degradation, and ER-phagy. Prolonged or severe ERS may exceed the adaptive capacity of cells, leading to dysregulation in apoptosis and autophagy—key pathogenic factors contributing to chondrocyte damage and OA progression. This review examines the relationship between ERS in OA chondrocytes and both apoptosis and autophagy in order to identify potential therapeutic targets and strategies for prevention and treatment of OA.

骨关节炎（OA）的主要特征是关节软骨退化，发病率和致残率都很高。软骨细胞作为软骨内唯一的细胞类型，其功能表型对 OA 的发展至关重要。由于软骨的无血管性质及其有限的再生能力，损伤后的修复面临着巨大的挑战。各种细胞应激因素，包括缺氧、营养匮乏、氧化应激和胶原突变，都可能导致折叠错误的蛋白质在内质网（ER）中堆积，造成ER应激（ERS）。为了恢复ER的平衡以及细胞的活力和功能，一系列适应机制被触发，包括未折叠蛋白反应（UPR）、ER相关降解（ERAD）和ER吞噬。长期或严重的ERS可能会超出细胞的适应能力，导致细胞凋亡和自噬失调--这是导致软骨细胞损伤和OA进展的主要致病因素。本综述探讨了 OA 软骨细胞的 ERS 与细胞凋亡和自噬之间的关系，以确定预防和治疗 OA 的潜在治疗靶点和策略。

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