Cell Stress & Chaperones最新文献

{"title":"Partial limitation of cellular functions and compensatory modulation of unfolded protein response pathways caused by double-knockout of ATF6α and ATF6β","authors":"Ryoko Akai ,&nbsp;Hisayo Hamashima ,&nbsp;Michiko Saito ,&nbsp;Kenji Kohno ,&nbsp;Takao Iwawaki","doi":"10.1016/j.cstres.2023.11.002","DOIUrl":"https://doi.org/10.1016/j.cstres.2023.11.002","url":null,"abstract":"<div><p>Mammalian cells have three types of endoplasmic reticulum (ER) stress-sensing molecules: ATF6, IRE1, and PERK. Among these, ATF6 is unique in that it is processed in an ER-stress-specific manner and functions as a transcription factor for the activation of anti-ER stress genes (such as BiP). ATF6 is known to have two homologues, ATF6α and ATF6β, and a greater understanding of their functions has been achieved through analyses using cultured cells. Physiological functions are also gradually being investigated in mice lacking ATF6α or ATF6β. However, little is known about the effects on mouse organisms of the deletion of both the ATF6α and ATF6β genes, since such double-knockout (DKO) mice suffer embryonic lethality at an early developmental stage. In this study, we generated and analyzed ATF6 DKO mice in which embryonic lethality was evaded by using Cre/loxP technology. Pancreatic β cell-specific ATF6 DKO mice were born normally and lived without dysregulation of blood-glucose levels but had a reduced tolerance to glucose. Islets isolated from ATF6 DKO mice also showed low production and secretion of insulin and mild enhancement of IRE1 and PERK activity. We further examined the developmental abnormalities of systemic ATF6 DKO mice. The phenotypes of ATF6α^−/−; ATF6β^−/− mice were similar to those previously reported, but ATF6α^+/−; ATF6β^−/− and ATF6α^−/−; ATF6β^+/− mice showed embryonic lethality at middle developmental stages, unlike those reported. Analysis of embryonic fibroblasts derived from these mice revealed that ATF6α and ATF6β have a gene-dose-dependent functional redundancy and display distinct differences in their ability to induce BiP expression. (250 words)</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 1","pages":"Pages 34-48"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1355814523022423/pdfft?md5=0a26f91ad555e96cdde3e0902dd50c3e&pid=1-s2.0-S1355814523022423-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139694714","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":"Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway","authors":"Yanjie Lu ,&nbsp;Die Cheng ,&nbsp;Jiayu Pang ,&nbsp;Yuqiao Peng ,&nbsp;Shunkang Jin ,&nbsp;Xinyu Zhang ,&nbsp;Yuhong Li ,&nbsp;Yanzhen Zuo","doi":"10.1016/j.cstres.2024.02.001","DOIUrl":"10.1016/j.cstres.2024.02.001","url":null,"abstract":"<div><p>Chronic stress is a common emotional disorder in cancer patients. Chronic stress promotes progression of gastric cancer (GC) and leads to poor outcomes. However, the underlying mechanisms remain not clear. Herein, we explored the possible mechanisms of chronic stress in GC progression. The Cancer Genome Atlas (TCGA) datasets were analyzed for differentially expressed genes. Clinical data of GC were evaluated for their association with PlexinA1 using TCGA and Kaplan–Meier-plotter databases. Chronic stress of GC patients was evaluated using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Chronic unpredictable mild stress (CUMS) was used to induce chronic stress in mice. Gastric xenograft tumor was constructed using the sewing method. Chronic stress-like behaviors were assessed using light/dark box and tail suspension tests. Protein expression was detected using immunohistochemistry and Western blot analysis. Analyses of TCGA and the Kaplan–Meier-plotter databases showed that patients with high levels of PlexinA1 in GC had worse overall survival than those with low levels of PlexinA1. A total of 36 GC patients were enrolled in the study, and about 33% of the patients had chronic stress. Compared with patients without chronic stress, higher expression levels of adrenoceptor beta 2 and PlexinA1 were observed in patients with chronic stress. The tumor size in mice under CUMS was significantly increased compared with the control mice. Adrenoceptor beta 2, PlexinA1, N-cadherin, and alpha-smooth muscle actin, as well as Ki67 were highly expressed in the tumors of CUMS group. However, E-cadherin was lowly expressed in the tumors of CUMS group. Importantly, chemical sympathectomy with 6-hydroxydopamine or treatment with a selective β2 adrenergic receptor antagonist (ICI118,551) could reverse these effects. Our findings suggest that chronic stress plays an important role in GC progression and there is a potential for blocking the epinephrine-β2AR/PlexinA1 pathway in the treatment of GC.</p></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 1","pages":"Pages 201-215"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S135581452400049X/pdfft?md5=a635e13ec33c557e67cd22186bd9fc94&pid=1-s2.0-S135581452400049X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706203","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":"Human HSP70-escort protein 1 (hHep1) interacts with negatively charged lipid bilayers and cell membranes.","authors":"Milene N O Moritz, Paulo R Dores-Silva, Amanda L S Coto, Heloísa S Selistre-de-Araújo, Andrei Leitão, David M Cauvi, Antonio De Maio, Serena Carra, Júlio Cesar Borges","doi":"10.1007/s12192-023-01394-1","DOIUrl":"https://doi.org/10.1007/s12192-023-01394-1","url":null,"abstract":"<p><p>Human Hsp70-escort protein 1 (hHep1) is a cochaperone that assists in the function and stability of mitochondrial HSPA9. Similar to HSPA9, hHep1 is located outside the mitochondria and can interact with liposomes. In this study, we further investigated the structural and thermodynamic behavior of interactions between hHep1 and negatively charged liposomes, as well as interactions with cellular membranes. Our results showed that hHep1 interacts peripherally with liposomes formed by phosphatidylserine and cardiolipin and remains partially structured, exhibiting similar affinities for both. In addition, after being added to the cell membrane, recombinant hHep1 was incorporated by cells in a dose-dependent manner. Interestingly, the association of HSPA9 with hHep1 improved the incorporation of these proteins into the lipid bilayer. These results demonstrated that hHep1 can interact with lipids also present in the plasma membrane, indicating roles for this cochaperone outside of mitochondria.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"28 6","pages":"1001-1012"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471568","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":"Protein quality control: from molecular mechanisms to therapeutic intervention-EMBO workshop, May 21-26 2023, Srebreno, Croatia.","authors":"Christian Münch, Janine Kirstein","doi":"10.1007/s12192-023-01383-4","DOIUrl":"https://doi.org/10.1007/s12192-023-01383-4","url":null,"abstract":"<p><p>Protein quality control pathways ensure a functional proteome and rely on a complex proteostasis network (PN) that is composed of molecular chaperones and proteases. Failures in the PN can lead to a broad spectrum of diseases, including neurodegenerative disorders like Alzheimer's, Parkinson's, and a range of motor neuron diseases. The EMBO workshop \"Protein quality control: from molecular mechanisms to therapeutic intervention\" covered all aspects of protein quality control from underlying molecular mechanisms of chaperones and proteases to stress signaling pathways and medical implications. This report summarizes the workshop and highlights selected presentations.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"28 6","pages":"631-640"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471712","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":"Melissa officinalis extract suppresses endoplasmic reticulum stress-induced apoptosis in the brain of hypothyroidism-induced rats exposed to γ-radiation.","authors":"Omayma Ar Abo-Zaid, Fatma Sm Moawed, Eman Fs Taha, Esraa S A Ahmed, Ragaa Sm Kawara","doi":"10.1007/s12192-023-01363-8","DOIUrl":"https://doi.org/10.1007/s12192-023-01363-8","url":null,"abstract":"<p><p>The purpose of this study was to demonstrate the neuroprotective effect of Melissa officinalis extract (MEE) against brain damage associated with hypothyroidism induced by propylthiouracil (PTU) and/or γ-radiation (IR) in rats. Hypothyroidism induction and/or exposure to IR resulted in a significant decrease in the serum levels of T3 and T4 associated with increased levels of lipid peroxidation end product, malondialdehyde (MDA), and nitrites (NO) in the brain tissue homogenate. Also, hypothyroidism and /or exposure to IR markedly enhance the endoplasmic reticulum stress by upregulating the gene expressions of the protein kinase RNA-like endoplasmic reticulum kinase (PERK), activated transcription factor 6 (ATF6), endoplasmic reticulum-associated degradation (ERAD), and CCAAT/enhancer-binding protein homologous protein (CHOP) in the brain tissue homogenate associated with a proapoptotic state which indicated by the overexpression of Bax, BCl2, and caspase-12 that culminates in brain damage. Meanwhile, the PTU and /or IR-exposed rats treated with MEE reduced oxidative stress and ERAD through ATF6. Also, the MEE treatment prevented the Bax and caspase-12 gene expression from increasing. This treatment in hypothyroid animals was associated with neuronal protection as indicated by the downregulation in the gene expressions of the microtubule-associated protein tau (MAPT) and amyloid precursor protein (APP) in the brain tissue. Furthermore, the administration of MEE ameliorates the histological structure of brain tissue. In conclusion, MEE might prevent hypothyroidism-induced brain damage associated with oxidative stress and endoplasmic reticulum stress.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"28 6","pages":"709-720"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471746","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":"Transitions.","authors":"R William Currie","doi":"10.1007/s12192-023-01396-z","DOIUrl":"https://doi.org/10.1007/s12192-023-01396-z","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"28 6","pages":"597-598"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471881","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":"Genomic loss of the HSP70cA gene in the vertebrate lineage.","authors":"Alisha Merchant, Bradly I Ramirez, Melinda N Reyes, Dysocheata Van, Marilin Martinez-Colin, Damilola O Ojo, Esmeralda L Mazuca, Heidi J De La O, Abigayle M Glenn, Claudia G Lira, Hashimul Ehsan, Ermeng Yu, Gen Kaneko","doi":"10.1007/s12192-023-01370-9","DOIUrl":"10.1007/s12192-023-01370-9","url":null,"abstract":"<p><p>Metazoan 70 kDa heat shock protein (HSP70) genes have been classified into four lineages: cytosolic A (HSP70cA), cytosolic B (HSP70cB), endoplasmic reticulum (HSP70er), and mitochondria (HSP70m). Because previous studies have identified no HSP70cA genes in vertebrates, we hypothesized that this gene was lost on the evolutionary path to vertebrates. To test this hypothesis, the present study conducted a comprehensive database search followed by phylogenetic and synteny analyses. HSP70cA genes were found in invertebrates and in two of the three subphyla of Chordata, Cephalochordata (lancelets) and Tunicata (tunicates). However, no HSP70cA gene was found in the genomes of Craniata (another subphylum of Chordata; lamprey, hagfish, elephant shark, and coelacanth), suggesting the loss of the HSP70cA gene in the early period of vertebrate evolution. Synteny analysis using available genomic resources indicated that the synteny around the HSP70 genes was generally conserved between tunicates but was largely different between tunicates and lamprey. These results suggest the presence of dynamic chromosomal rearrangement in early vertebrates that possibly caused the loss of the HSP70cA gene in the vertebrate lineage.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"1053-1067"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10367834","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":"A review on oligomeric polydispersity and oligomers-dependent holding chaperone activity of the small heat-shock protein IbpB of Escherichia coli.","authors":"Md Azaharuddin, Anabadya Pal, Sangeeta Mitra, Rakhi Dasgupta, Tarakdas Basu","doi":"10.1007/s12192-023-01392-3","DOIUrl":"10.1007/s12192-023-01392-3","url":null,"abstract":"<p><p>Inclusion body-associated proteins IbpA and IbpB of MW 16 KDa are the two small heat-shock proteins (sHSPs) of Escherichia coli, and they have only holding, but not folding, chaperone activity. In vitro holdase activity of IbpB is more than that of IbpA, and in combination, they synergise. Both IbpA and IbpB monomers first form homodimers, which as building blocks subsequently oligomerize to make heavy oligomers with MW of MDa range; for IbpB, the MW range of heavy oligomers is 2.0-3.0 MDa, whereas for IbpA oligomers, the values in MDa are not so specified/reported. By temperature upshift, such large oligomers of IbpB, but not of IbpA, dissociate to make relatively small oligomeric assemblies of MW around 600-700KDa. The larger oligomers of IbpB are assumed to be inactive storage form, which on facing heat or oxidative stress dissociate into smaller oligomers of ATP-independent holding chaperone activity. These smaller oligomers bind with stress-induced partially denatured/unfolded and thereby going to be aggregated proteins, to give them protection against permanent damage and aggregation. On withdrawal of stress, IbpB transfers the bound substrate protein to the ATP-dependent bi-chaperone system DnaKJE-ClpB, having both holdase and foldase properties, to finally refold the protein. Of the two sHSPs IbpA and IbpB of E. coli, this review covers the recent advances in research on IbpB only.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"689-696"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421044","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":"SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway.","authors":"Rabab S Hamad, Hayder M Al-Kuraishy, Athanasios Alexiou, Marios Papadakis, Eman A Ahmed, Hebatallah M Saad, Gaber El-Saber Batiha","doi":"10.1007/s12192-023-01379-0","DOIUrl":"10.1007/s12192-023-01379-0","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leading to pulmonary and extra-pulmonary manifestations due to the development of oxidative stress (OS) and hyperinflammation. The underlying cause for OS and hyperinflammation in COVID-19 may be related to the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidative responses and cellular homeostasis. The Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm and OS in COVID-19. Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Hence, this review aimed to reveal the potential role of the Nrf2 pathway and its activators in the management of COVID-19. As well, we tried to revise the mechanistic role of the Nrf2 pathway in COVID-19.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"657-673"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093120","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":"Heat shock protein 27 in the pathogenesis of COVID-19 and non-COVID acute respiratory distress syndrome.","authors":"Michael H Chiu, Benjamin Gershkovich, Ian-Ling Yu, Edward R O'Brien, Jingti Deng, Braedon McDonald","doi":"10.1007/s12192-023-01381-6","DOIUrl":"10.1007/s12192-023-01381-6","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure in intensive care units that has increased dramatically as a result of the COVID-19 pandemic. In both COVID-19 and non-COVID ARDS, the pathogenesis of lung injury involves local (pulmonary) and systemic inflammation, leading to impaired gas exchange, requirement for mechanical ventilation, and a high risk of mortality. Heat shock protein 27 (HSP27) is a chaperone protein expressed in times of cell stress with roles in modulation of systemic inflammation via the NF-κB pathway. Given its important role as a modulator of inflammation, we sought to investigate the role of HSP27 and its associated auto-antibodies in ARDS caused by both SARS-CoV-2 and non-COVID etiologies. A total of 68 patients admitted to the intensive care unit with ARDS requiring mechanical ventilation were enrolled in a prospective, observational study that included 22 non-COVID-19 and 46 COVID-19 patients. Blood plasma levels of HSP27, anti-HSP27 auto-antibody (AAB), and cytokine profiles were measured on days 1 and 3 of ICU admission along with clinical outcome measures. Patients with COVID-19 ARDS displayed significantly higher levels of HSP27 in plasma, and a higher ratio of HSP27:AAB on both day 1 and day 3 of ICU admission. In patients with COVID-19, higher levels of circulating HSP27 and HSP27:AAB ratio were associated with a more severe systemic inflammatory response and adverse clinical outcomes including more severe hypoxemic respiratory failure. These findings implicate HSP27 as a marker of advanced pathogenesis of disease contributing to the dysregulated systemic inflammation and worse clinical outcomes in COVID-19 ARDS, and therefore may represent a potential therapeutic target.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":" ","pages":"877-887"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590271","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}