Cell Stress & Chaperones最新文献

{"title":"Previously unrecognized and potentially consequential challenges facing Hsp90 inhibitors in cancer clinical trials","authors":"Cheng Chang,&nbsp;Xin Tang,&nbsp;David T. Woodley,&nbsp;Mei Chen,&nbsp;Wei Li","doi":"10.1016/j.cstres.2024.08.002","DOIUrl":"10.1016/j.cstres.2024.08.002","url":null,"abstract":"<div><p>Targeting the heat shock protein-90 (Hsp90) chaperone machinery in various cancers with 200 monotherapy or combined-therapy clinical trials since 1999 has not yielded any success of food and drug administration approval. Blames for the failures were unanimously directed at the Hsp90 inhibitors or tumors or both. However, analyses of recent cellular and genetic studies together with the Hsp90 data from the Human Protein Atlas database suggest that the vast variations in Hsp90 expression among different organs in patients might have been the actual cause. It is evident now that Hsp90β is the root of dose-limiting toxicity (DLT), whereas Hsp90α is a buffer of penetrated Hsp90 inhibitors. The more Hsp90α, the safer Hsp90β, and the lower DLT are for the host. Unfortunately, the dramatic variations of Hsp90, from total absence in the eye, muscle, pancreas, and heart to abundance in reproduction organs, lung, liver, and gastrointestinal track, would cause the selection of any fair toxicity biomarker and an effective maximum tolerable dose (MTD) of Hsp90 inhibitor extremely challenging. In theory, a safe MTD for the organs with high Hsp90 could harm the organs with low Hsp90. In reverse, a safe MTD for organs with low or undetectable Hsp90 would have little impact on the tumors, whose cells exhibit average 3–7% Hsp90 over the average 2–3% Hsp90 in normal cells. Moreover, not all tumor cell lines tested follow the “inhibitor binding-client protein degradation” paradigm. It is likely why the oral Hsp90 inhibitor TAS-16 (Pimitespib), which bypasses blood circulation and other organs, showed some beneficiary efficacy by conveniently hitting tumors along the gastrointestinal track. The critical question is what the next step will be for the Hsp90 chaperone as a cancer therapeutic target.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 5","pages":"Pages 642-653"},"PeriodicalIF":3.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001135/pdfft?md5=bb6803984815a0bac43a72463f215aff&pid=1-s2.0-S1355814524001135-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055099","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":"Retraction notice to “Role of mitochondria in doxorubicin-mediated cardiotoxicity: From molecular mechanisms to therapeutic strategies” [Cell Stress Chaperones. 2024;29:349-357]","authors":"Tianen Wang ,&nbsp;Guoli Xing ,&nbsp;Tong Fu ,&nbsp;Yanchun Ma ,&nbsp;Qi Wang ,&nbsp;Shuxiang Zhang ,&nbsp;Xing Chang ,&nbsp;Ying Tong","doi":"10.1016/j.cstres.2024.08.003","DOIUrl":"10.1016/j.cstres.2024.08.003","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 5","pages":"Page 641"},"PeriodicalIF":3.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001147/pdfft?md5=07a98022025dda4830fa82fbcc53b621&pid=1-s2.0-S1355814524001147-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055100","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":"Cracking the chaperone code through the computational microscope","authors":"Federica Guarra ,&nbsp;Cristiano Sciva ,&nbsp;Giorgio Bonollo ,&nbsp;Chiranjeevi Pasala ,&nbsp;Gabriela Chiosis ,&nbsp;Elisabetta Moroni ,&nbsp;Giorgio Colombo","doi":"10.1016/j.cstres.2024.08.001","DOIUrl":"10.1016/j.cstres.2024.08.001","url":null,"abstract":"<div><p>The heat shock protein 90 kDa (Hsp90) chaperone machinery plays a crucial role in maintaining cellular homeostasis. Beyond its traditional role in protein folding, Hsp90 is integral to key pathways influencing cellular function in health and disease. Hsp90 operates through the modular assembly of large multiprotein complexes, with their composition, stability, and localization adapting to the cell's needs. Its functional dynamics are finely tuned by ligand binding and post-translational modifications (PTMs). Here, we discuss how to disentangle the intricacies of the complex code that governs the crosstalk between dynamics, binding, PTMs, and the functions of the Hsp90 machinery using computer-based approaches. Specifically, we outline the contributions of computational and theoretical methods to the understanding of Hsp90 functions, ranging from providing atomic-level insights into its dynamics to clarifying the mechanisms of interactions with protein clients, cochaperones, and ligands. The knowledge generated in this framework can be actionable for the design and development of chemical tools and drugs targeting Hsp90 in specific disease-associated cellular contexts. Finally, we provide our perspective on how computation can be integrated into the study of the fine-tuning of functions in the highly complex Hsp90 landscape, complementing experimental methods for a comprehensive understanding of this important chaperone system.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 5","pages":"Pages 626-640"},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S135581452400110X/pdfft?md5=40b052791cb355c02a3a748cc96b76cd&pid=1-s2.0-S135581452400110X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981812","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(24)00112-3","DOIUrl":"10.1016/S1355-8145(24)00112-3","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Page i"},"PeriodicalIF":3.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001123/pdfft?md5=d0ab9a433358e73f3f61e967004b35fd&pid=1-s2.0-S1355814524001123-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998072","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(24)00111-1","DOIUrl":"10.1016/S1355-8145(24)00111-1","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Page OFC"},"PeriodicalIF":3.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001111/pdfft?md5=2c34f2ccc9ca9400a9b3e50aa4a951f8&pid=1-s2.0-S1355814524001111-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998071","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":"Unraveling the intricacies of cold-inducible RNA-binding protein: A comprehensive review","authors":"","doi":"10.1016/j.cstres.2024.07.001","DOIUrl":"10.1016/j.cstres.2024.07.001","url":null,"abstract":"<div><p>Cold-inducible RNA-binding protein (CIRP) is a versatile RNA-binding protein, pivotal in modulating cellular responses to diverse stress stimuli including cold shock, ultraviolet radiation, hypoxia, and infections, with a principal emphasis on cold stress. The temperature range of 32–34 °C is most suitable for CIRP expression. The human CIRP is an 18–21 kDa polypeptide containing 172 amino acids coded by a gene located on chromosome 19p13.3. CIRP has an RNA-recognition motif (RRM) and an arginine-rich motif (RGG), both of which have roles in coordinating numerous cellular activities. CIRP itself also undergoes conformational changes in response to diverse environmental stress. Transcription factors such as hypoxia-inducible factor 1 alpha and nuclear factor-kappa B have been implicated in coordinating CIRP transcription in response to specific stimuli. The potential of CIRP to relocate from the nucleus to the cytoplasm upon exposure to different stimuli enhances its varied functional roles across different cellular compartments. The different functions include decreasing nutritional demand, apoptosis suppression, modulation of translation, and preservation of cytoskeletal integrity at lower temperatures. This review explores the diverse functions and regulatory mechanisms of CIRP, shedding light on its involvement in various cellular processes and its implications for human health and disease.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Pages 615-625"},"PeriodicalIF":3.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001093/pdfft?md5=acb7892ea29c2248f10d390b0323f4e9&pid=1-s2.0-S1355814524001093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537667","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":"Genome-wide DNA methylation profiles regulate distinct heat stress response in zebu (Bos indicus) and crossbred (Bos indicus × Bos taurus) cattle","authors":"Basavaraj Sajjanar ,&nbsp;Mohd Tanzeel Aalam ,&nbsp;Owais Khan ,&nbsp;Sujoy K Dhara ,&nbsp;Jyotirmoy Ghosh ,&nbsp;Ravi Kumar Gandham ,&nbsp;Praveen K Gupta ,&nbsp;Pallab Chaudhuri ,&nbsp;Triveni Dutt ,&nbsp;Gyanendra Singh ,&nbsp;Bishnu Prasad Mishra","doi":"10.1016/j.cstres.2024.06.005","DOIUrl":"10.1016/j.cstres.2024.06.005","url":null,"abstract":"<div><p>Epigenetic variations result from long-term adaptation to environmental factors. The <em>Bos indicus</em> (zebu) adapted to tropical conditions, whereas <em>Bos taurus</em> adapted to temperate conditions; hence native zebu cattle and its crossbred (<em>B indicus</em> × <em>B taurus</em>) show differences in responses to heat stress. The present study evaluated genome-wide DNA methylation profiles of these two breeds of cattle that may explain distinct heat stress responses. Physiological responses to heat stress and estimated values of Iberia heat tolerance coefficient and Benezra's coefficient of adaptability revealed better relative thermotolerance of Hariana compared to the Vrindavani cattle. Genome-wide DNA methylation patterns were different for Hariana and Vrindavani cattle. The comparison between breeds indicated the presence of 4599 significant differentially methylated CpGs with 756 hypermethylated and 3845 hypomethylated in Hariana compared to the Vrindavani cattle. Further, we found 79 genes that showed both differential methylation and differential expression that are involved in cellular stress response functions. Differential methylations in the microRNA coding sequences also revealed their functions in heat stress responses. Taken together, epigenetic differences represent the potential regulation of long-term adaptation of Hariana (<em>B indicus</em>) cattle to the tropical environment and relative thermotolerance.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Pages 603-614"},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001081/pdfft?md5=27758b5ec87f0e9fa45caa56cc3037e8&pid=1-s2.0-S1355814524001081-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466372","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":"The influence of HSP inducers on salinity stress in sterlet sturgeon (Acipenser ruthenus): In vitro study on HSP expression, immune responses, and antioxidant capacity","authors":"Sevda Zarei ,&nbsp;Hossein Ghafouri ,&nbsp;Leila Vahdatiraad ,&nbsp;Behrooz Heidari","doi":"10.1016/j.cstres.2024.06.004","DOIUrl":"10.1016/j.cstres.2024.06.004","url":null,"abstract":"<div><p>Heat shock proteins (HSPs) play a crucial role in antioxidant systems, immune responses, and enzyme activation during stress conditions. Salinity changes can cause stress and energy expenditure in fish, resulting in mortality, especially in fingerlings. The purpose of this study was to examine the relationship between salinity and HSPs in stressed fish by assessing the effects of various HSP inducers (HSPis), including Pro-Tex® (800 mM), amygdalin (80 mM), and a novel synthetic compound derived from pirano piranazole (80 µM), on isolated cells from Sterlet Sturgeon (<em>Acipenser ruthenus</em>) exposed to 13 ‰ salinity (S13). After liver, kidney, and gill cells were cultured, the HSPi compounds were treated <em>in vitro</em> in the presence and absence of salinity. The expression patterns of HSP27, HSP70, and HSP90 were assessed by Western blotting. Biochemical enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), cortisol levels, and immune parameters (component 3, immunoglobulin M, and lysozyme) were measured before and after treatment with HSPis and HSPi + S13. According to these findings, HSPis positively modulate HSP expression, immune responses, and antioxidant levels. Furthermore, they increased <em>in vitro</em> cell survival by maintaining cortisol levels and biochemical enzyme activities in <em>A. ruthenus</em> under saline conditions (<em>P</em> &lt; 0.0001). In conclusion, HSPis can increase <em>A. ruthenus</em> resistance to salinity stress. However, the results also indicated that these compounds can reverse the adverse effects of salinity. The effectiveness of this approach depends on further research into the effects of these ecological factors on the health status of the species, especially <em>in vivo</em> and in combination with other stresses.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Pages 552-566"},"PeriodicalIF":3.3,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S135581452400107X/pdfft?md5=2f833a27219496ed1b914784a7d3a04a&pid=1-s2.0-S135581452400107X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442105","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":"Genome-wide identification of the HSP70 genes in Pacific oyster Magallana gigas and their response to heat stress","authors":"Hongbo Lu ,&nbsp;Chang Liu ,&nbsp;Chuanyan Yang ,&nbsp;Zhaoyu He ,&nbsp;Lingling Wang ,&nbsp;Linsheng Song","doi":"10.1016/j.cstres.2024.06.002","DOIUrl":"10.1016/j.cstres.2024.06.002","url":null,"abstract":"<div><p>Heat shock protein 70 (HSP70), the most prominent and well-characterized stress protein in animals, plays an important role in assisting animals in responding to various adverse conditions. In the present study, a total of 113 HSP70 gene family members were identified in the updated genome of <em>Magallana gigas</em> (designated <em>Mg</em>HSP70) (previously known as <em>Crassostrea gigas</em>). There were 75, 12, 11, and 8 HSP70s located in the cytoplasm, nucleus, mitochondria, and endoplasmic reticulum, respectively, and 7 HSP70s were located in both the nucleus and cytoplasm. Among 113 <em>Mg</em>HSP70 genes, 107 were unevenly distributed in 8 chromosomes of <em>M. gigas</em> with the greatest number in chromosome 07 (61 genes, 57.01%). The <em>Mg</em>HSP70 gene family members were mainly assigned into five clusters, among which the HSPa12 subfamily underwent lineage-specific expansion, consisting of 89 members. A total of 68 <em>Mg</em>HSP70 genes (60.18%) were tandemly duplicated and formed 30 gene pairs, among which 14 gene pairs were under strong positive selection. In general, the expression of <em>Mg</em>HSP70s was tissue-specific, with the highest expression in labial palp and gill and the lowest expression in adductor muscle and hemocytes. There were 35, 31, and 47 significantly upregulated genes at 6, 12, and 24 h after heat shock treatment (28 °C), respectively. The expression patterns of different tandemly duplicated genes exhibited distinct characteristics after shock treatment, indicating that these genes may have different functions. Nevertheless, genes within the same tandemly duplicated group exhibit similar expression patterns. Most of the tandemly duplicated HSP70 gene pairs showed the highest expression levels at 24 h. This study provides a comprehensive description of the <em>Mg</em>HSP70 gene family in <em>M. gigas</em> and offers valuable insights into the functions of HSP70 in the mollusc adaptation of oysters to environmental stress.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Pages 589-602"},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001056/pdfft?md5=ec23a97084c8a16561a542b74788cdac&pid=1-s2.0-S1355814524001056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440200","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":"Biochemical characterization of ClpB and DnaK from Anaplasma phagocytophilum","authors":"Chathurange B. Ranaweera ,&nbsp;Sunitha Shiva ,&nbsp;Swetha Madesh ,&nbsp;Deepika Chauhan ,&nbsp;Roman R. Ganta ,&nbsp;Michal Zolkiewski","doi":"10.1016/j.cstres.2024.06.003","DOIUrl":"10.1016/j.cstres.2024.06.003","url":null,"abstract":"<div><p><em>Anaplasma phagocytophilum</em> is an intracellular tick-transmitted bacterial pathogen that infects neutrophils in mammals and causes granulocytic anaplasmosis. In this study, we investigated the molecular chaperones ClpB and DnaK from <em>A. phagocytophilum</em>. In <em>Escherichia coli</em>, ClpB cooperates with DnaK and its co-chaperones DnaJ and GrpE in ATP-dependent reactivation of aggregated proteins. Since ClpB is not produced in metazoans, it is a promising target for developing antimicrobial therapies, which generates interest in studies on that chaperone’s role in pathogenic bacteria. We found that ClpB and DnaK are transcriptionally upregulated in <em>A. phagocytophilum</em> 3–5 days after infection of human HL-60 and tick ISE6 cells, which suggests an essential role of the chaperones in supporting the pathogen’s intracellular life cycle. Multiple sequence alignments show that <em>A. phagocytophilum</em> ClpB and DnaK contain all structural domains that were identified in their previously studied orthologs from other bacteria. Both <em>A. phagocytophilum</em> ClpB and DnaK display ATPase activity, which is consistent with their participation in the ATP-dependent protein disaggregation system. However, despite a significant sequence similarity between the chaperones from <em>A. phagocytophilum</em> and those from <em>E. coli</em>, the former were not as effective as their <em>E. coli</em> orthologs during reactivation of aggregated proteins <em>in vitro</em> and in supporting the survival of <em>E. coli</em> cells under heat stress. We conclude that the <em>A. phagocytophilum</em> chaperones might have evolved with distinct biochemical properties to maintain the integrity of pathogenic proteins under unique stress conditions of an intracellular environment of host cells.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 4","pages":"Pages 540-551"},"PeriodicalIF":3.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814524001068/pdfft?md5=49daff0ee5c7e6a52943d2057ee3c41f&pid=1-s2.0-S1355814524001068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440199","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}