{"title":"Quantitative proteomic analyses uncover regulatory roles of Nrf2 in human endothelial cells.","authors":"Karan Naresh Amin, Palanichamy Rajaguru, Takayoshi Suzuki, Koustav Sarkar, Kumar Ganesan, Kunka Mohanram Ramkumar","doi":"10.1007/s12192-023-01366-5","DOIUrl":"10.1007/s12192-023-01366-5","url":null,"abstract":"<p><p>Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional regulator, is the predominant factor in modulating oxidative stress and other cellular signaling responses. Studies from our lab and others highlighted that activation of the Nrf2 pathway by small molecules improves endothelial function by suppressing oxidative and endoplasmic reticulum (ER) stress. However, the exact mechanisms by which Nrf2 elicits these effects are unknown. In the present study, we developed CRISPR/Cas9-mediated Nrf2 knocked-out human endothelial cells, and proteomic signature was studied using LC-MS/MS. We identified 723 unique proteins, of which 361 proteins were found to be differentially regulated and further screened in the Nrf2ome online database, where we identified a highly interconnected signaling network in which 70 proteins directly interact with Nrf2. These proteins were found to regulate some key cellular and metabolic processes in the regulation actin cytoskeleton, ER stress, angiogenesis, inflammation, Hippo signaling pathway, and epidermal growth factor/fibroblast growth factor (EGF/FGF) signaling pathway. Our findings suggest the role of Nrf2 in maintaining endothelium integrity and its relationship with the crucial cellular processes which help develop novel therapeutics against endothelial dysfunction and its associated complications.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223676","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}
Cell Stress & ChaperonesPub Date : 2023-11-01Epub Date: 2023-11-25DOI: 10.1007/s12192-023-01394-1
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
{"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":"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":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138433481","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}
Michael H Chiu, Benjamin Gershkovich, Ian-Ling Yu, Edward R O'Brien, Jingti Deng, Braedon McDonald
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471566","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}
Cell Stress & ChaperonesPub Date : 2023-11-01Epub Date: 2023-11-23DOI: 10.1007/s12192-023-01390-5
Dongbin Ma, Xuan Wang, Jia Liu, Yang Cui, Shuang Luo, Fanchen Wang
{"title":"The development of necroptosis: what we can learn.","authors":"Dongbin Ma, Xuan Wang, Jia Liu, Yang Cui, Shuang Luo, Fanchen Wang","doi":"10.1007/s12192-023-01390-5","DOIUrl":"10.1007/s12192-023-01390-5","url":null,"abstract":"<p><p>Necroptosis is a new type of programmed cell death discovered in recent years, playing an important role in various diseases. Since it was conceptualized in 2005, research on necroptosis has developed rapidly. However, few bibliometric analyses have provided a comprehensive overview of the field. This study aimed to employ a bibliometric analysis to assess necroptosis research's current status and hotspot, highlight landmark findings, and orientate future research. A total of 3993 publications from the WoSCC were collected for this study. Multiple tools were used for bibliometric analysis and data visualization, including an online website, VOSviewer, CiteSpace, and HistCite. Publications related to necroptosis have increased significantly annually, especially in the last 5 years. Globally, the USA and Harvard University are the most outstanding countries and institutions in this field, respectively. The academic groups managed by Peter Vandenabeele and Junying Yuan both have permanent and intensive research on necroptosis. Cell Death and Differentiation is the most vital journal in this field. The molecular mechanisms of necroptosis and its role in disease are the focus of current research, while the crosstalk between programmed cell death is an emerging direction in the field. The \"reactive oxygen species\", \"innate immunity\", and \"programmed cell death\" may be potential research hotspots. Our results present a comprehensive knowledge map and explore research trends. Researchers and funding agencies on necroptosis can obtain helpful references from our study.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294749","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}
Sercan Kaya, Tuba Yalcın, Ahmet Tektemur, Tuncay Kuloğlu
{"title":"N-Acetylcysteine may exert hepatoprotective effect by regulating Meteorin-Like levels in Adriamycin-induced liver injury.","authors":"Sercan Kaya, Tuba Yalcın, Ahmet Tektemur, Tuncay Kuloğlu","doi":"10.1007/s12192-023-01376-3","DOIUrl":"https://doi.org/10.1007/s12192-023-01376-3","url":null,"abstract":"<p><p>Adriamycin (ADR) is an important chemotherapeutic drug, but it has serious side effects such as hepatotoxicity. This study aimed to evaluate whether N-acetylcysteine (NAC) has hepatoprotective effects against ADR-induced hepatotoxicity in rats. In addition, it was aimed to determine how Meteorin-Like (MtrnL), which has pleiotropic effects on immunology, inflammation, and metabolism, is affected by ADR and/or NAC applications in liver tissue. 28 rats were randomly assigned to one of four equal groups in the study: control (no treatment), NAC (150 mg/kg/day of NAC intraperitoneally (i.p), ADR (15 mg/kg only on the first day of the experiment), and ADR + NAC (ADR 15 mg/kg on the first day of the experiment + 150 mg/kg/day NAC i.p). After 15 days, liver enzyme levels in serum, oxidant/antioxidant parameters in liver tissue, histopathological changes, caspase 3 (Casp3) and heat shock protein 70 (HSP-70) immunoreactivities, and MtrnL levels were examined. Histopathological changes, liver enzyme levels, as well as HSP-70, and Casp3 immunoreactivities increased due to ADR application. Additionally, MtrnL levels in liver tissue were significantly increased as a result of ADR application. However, it was detected that the NAC application significantly regulated the ADR-induced changes. Furthermore, it was determined that NAC administration regulated the changes in ADR-induced oxidative stress parameters. We propose that NAC may exert a hepatoprotective effect by regulating ADR-induced altered oxidative stress parameters, MtrnL levels, Casp3, and HSP-70 immunoreactivities in the liver.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471704","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}
Haotian Chen, Chen Chen, Yuhui Qin, Lei Wang, Jie Zheng, Fabao Gao
{"title":"Protective effects of epigallocatechin-3-gallate counteracting the chronic hypobaric hypoxia-induced myocardial injury in plain-grown rats at high altitude.","authors":"Haotian Chen, Chen Chen, Yuhui Qin, Lei Wang, Jie Zheng, Fabao Gao","doi":"10.1007/s12192-023-01386-1","DOIUrl":"https://doi.org/10.1007/s12192-023-01386-1","url":null,"abstract":"<p><p>Exposure to hypobaric hypoxia (HH) environment causes stress to the body, especially the oxygen-consuming organs. Chronic HH conditions have adverse effects on the myocardium. Thus, we conducted this experiment and aim to evaluate such adverse effects and explore the therapeutic role of epigallocatechin-3-gallate (EGCG) in rats' heart under chronic HH conditions. For that purpose, we transported rats from plain to a real HH environment at high altitude for establishing the HH model. At high altitude, animals were treated with EGCG while the salidroside was used as the positive control. General physiological data were collected, and routine blood test results were analyzed. Cardiac magnetic resonance (CMR) was examined to assess the structural and functional changes of the heart. Serum levels of cardiac enzymes and pro-inflammatory cytokines were examined. Oxidative markers in the left ventricle (LV) were detected. Additionally, ultrastructural and histopathological changes and apoptosis of the LV were assessed. Furthermore, the antioxidant stress-relevant proteins nuclear factor E2-related factor 2 (Nrf2) and the heme oxygenase-1 (HO-1) were detected. The experiment revealed that EGCG treatment decreased HH-induced elevation of cardiac enzymes and relieved mitochondrial damage of the LV. Notably, EGCG treatment significantly alleviated oxidative stress in the LV and inflammatory response in the blood. Western blot confirmed that EGCG significantly upregulated Nrf2 and HO-1. Therefore, EGCG may be considered a promising natural compound for treating the HH-induced myocardial injuries.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471707","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}
Carlos Henrique de Lemos Muller, Cesar Eduardo Jacintho Moritz, Helena Trevisan Schroeder, Ana Maria Oliveira Battastini, Alvaro Reischak-Oliveira, Paulo Ivo Homem de Bittencourt Júnior, Giuseppe De Vito, Maurício Krause
{"title":"Influence of body composition and cardiorespiratory fitness on plasma HSP72, norepinephrine, insulin, and glucose responses to an acute aerobic exercise bout performed in the fed state.","authors":"Carlos Henrique de Lemos Muller, Cesar Eduardo Jacintho Moritz, Helena Trevisan Schroeder, Ana Maria Oliveira Battastini, Alvaro Reischak-Oliveira, Paulo Ivo Homem de Bittencourt Júnior, Giuseppe De Vito, Maurício Krause","doi":"10.1007/s12192-023-01364-7","DOIUrl":"https://doi.org/10.1007/s12192-023-01364-7","url":null,"abstract":"<p><p>Being overweight is already considered a metabolic risk factor, which can be overcome by increasing cardiorespiratory fitness (CRF). Acute exercise is known to induce changes in plasma hormones and heat shock proteins release. However, there is a lack of studies investigating the impact of body composition and CRF on these variables following acute aerobic exercise. To assess the influence of body composition and cardiorespiratory fitness on plasma heat shock protein 72 kDa (HSP72), norepinephrine (NE), insulin, and glucose responses to an acute aerobic exercise bout in the fed state. Twenty-four healthy male adults were recruited and allocated into three groups: overweight sedentary (n = 8), normal weight sedentary (n = 8), and normal weight active (n = 8). The volunteers performed an acute moderate exercise session on a treadmill at 70% of VO<sub>2</sub> peak. Blood samples were drawn at baseline, immediately post-exercise, and at 1-h post-exercise. The exercise session did not induce changes in HSP72 nor NE but changes in glucose and insulin were affected by body mass index. Also, subjects with elevated CRF maintain reduced NE through exercise. At baseline, the overweight sedentary group showed elevated NE, insulin, and glucose; these last two impacting the HOMA-IR index. Thirty minutes of aerobic exercise at 70% VO<sub>2</sub> peak, in the fed state, did not change the levels of plasma NE and HSP72. Elevated body composition seems to impact metabolic profile and increase sympathetic activity. Conversely, subjects with increased cardiorespiratory fitness seem to have attenuated sympathetic activity.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471720","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}
Heloina Nathalliê Mariano da Silva, Daniela Sayuri Mizobuti, Valéria Andrade Pereira, Guilherme Luiz da Rocha, Marcos Vinícius da Cruz, André Gustavo de Oliveira, Leonardo Reis Silveira, Elaine Minatel
{"title":"LED therapy plus idebenone treatment targeting calcium and mitochondrial signaling pathways in dystrophic muscle cells.","authors":"Heloina Nathalliê Mariano da Silva, Daniela Sayuri Mizobuti, Valéria Andrade Pereira, Guilherme Luiz da Rocha, Marcos Vinícius da Cruz, André Gustavo de Oliveira, Leonardo Reis Silveira, Elaine Minatel","doi":"10.1007/s12192-023-01369-2","DOIUrl":"https://doi.org/10.1007/s12192-023-01369-2","url":null,"abstract":"<p><p>Intracellular calcium dysregulation, oxidative stress, and mitochondrial dysfunction are some of the main pathway contributors towards disease progression in Duchenne muscular dystrophy (DMD). This study is aimed at investigating the effects of light emitting diode therapy (LEDT) and idebenone antioxidant treatment, applied alone or together in dystrophic primary muscle cells from mdx mice, the experimental model of DMD. Mdx primary muscle cells were submitted to LEDT and idebenone treatment and evaluated for cytotoxic effects and calcium and mitochondrial signaling pathways. LEDT and idebenone treatment showed no cytotoxic effects on the dystrophic muscle cells. Regarding the calcium pathways, after LEDT and idebenone treatment, a significant reduction in intracellular calcium content, calpain-1, calsequestrin, and sarcolipin levels, was observed. In addition, a significant reduction in oxidative stress level markers, such as H<sub>2</sub>O<sub>2</sub>, and 4-HNE levels, was observed. Regarding mitochondrial signaling pathways, a significant increase in oxidative capacity (by OCR and OXPHOS levels) was observed. In addition, the PGC-1α, SIRT-1, and PPARδ levels were significantly higher in the LEDT plus idebenone treated-dystrophic muscle cells. Together, the findings suggest that LEDT and idebenone treatment, alone or in conjunction, can modulate the calcium and mitochondrial signaling pathways, such as SLN, SERCA 1, and PGC-1α, contributing towards the improvement of the dystrophic phenotype in mdx muscle cells. In addition, data from the LEDT plus idebenone treatment showed slightly better results than those of each separate treatment in terms of SLN, OXPHOS, and SIRT-1.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471723","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":"Responses of multifunctional immune complement component 1q (C1q) and apoptosis-related genes in Macrophthalmus japonicus tissues and human cells following exposure to environmental pollutants.","authors":"Kiyun Park, Byoung-San Moon, Ihn-Sil Kwak","doi":"10.1007/s12192-023-01389-y","DOIUrl":"https://doi.org/10.1007/s12192-023-01389-y","url":null,"abstract":"<p><p>Apoptosis is a key defense process for multiple immune system functions, playing a central role in maintaining homeostasis and cell development. The purpose of this study was to evaluate the effects of environmental pollutant exposure on immune-related apoptotic pathways in crab tissues and human cells. To do this, we characterized the multifunctional immune complement component 1q (C1q) gene and analyzed C1q expression in Macrophthalmus japonicus crabs after exposure to di(2-ethylhexyl) phthalate (DEHP) or hexabromocyclododecanes (HBCDs). Moreover, the responses of apoptotic signal-related genes were observed in M. japonicus tissues and human cell lines (HEK293T and HCT116). C1q gene expression was downregulated in the gills and hepatopancreas of M. japonicus after exposure to DEHP or HBCD. Pollutant exposure also increased antioxidant enzyme activities and altered transcription of 15 apoptotic signaling genes in M. japonicus. However, patterns in apoptotic signaling in response to these pollutants differed in human cells. HBCD exposure generated an apoptotic signal (cleaved caspase-3) and inhibited cell growth in both cell lines, whereas DEHP exposure did not produce such a response. These results suggest that exposure to environmental pollutants induced different levels of immune-related apoptosis depending on the cell or tissue type and that this induction of apoptotic signaling may trigger an initiation of carcinogenesis in M. japonicus and in humans as consumers.</p>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471820","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}