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6. Proteomic Profiling Reveals Roles of Stress Response, Ca2+ Transient Dysregulation, and Novel Signaling Pathways in Alcohol‐Induced Cardiotoxicity.

Author

Liu, Rui, Sun, Fangxu, Forghani, Parvin, Armand, Lawrence C., Rampoldi, Antonio, Li, Dong, Wu, Ronghu, and Xu, Chunhui

Subjects
COMPLICATIONS of alcoholism, CARDIOTOXICITY, CELLULAR signal transduction, PSYCHOLOGICAL stress, TUMOR necrosis factors, BIOINFORMATICS, PROTEOMICS, QUANTITATIVE research, TREATMENT effectiveness, GENE expression profiling
Abstract

Background: Alcohol use in pregnancy increases the risk of abnormal cardiac development, and excessive alcohol consumption in adults can induce cardiomyopathy, contractile dysfunction, and arrhythmias. Understanding molecular mechanisms underlying alcohol‐induced cardiac toxicity could provide guidance in the development of therapeutic strategies. Methods: We have performed proteomic and bioinformatic analysis to examine protein alterations globally and quantitatively in cardiomyocytes derived from human‐induced pluripotent stem cells (hiPSC‐CMs) treated with ethanol (EtOH). Proteins in both cell lysates and extracellular culture media were systematically quantitated. Results: Treatment with EtOH caused severe detrimental effects on hiPSC‐CMs as indicated by significant cell death and deranged Ca2+ handling. Treatment of hiPSC‐CMs with EtOH significantly affected proteins responsible for stress response (e.g., GPX1 and HSPs), ion channel‐related proteins (e.g. ATP1A2), myofibril structure proteins (e.g., MYL2/3), and those involved in focal adhesion and extracellular matrix (e.g., ILK and PXN). Proteins involved in the TNF receptor‐associated factor 2 signaling (e.g., CPNE1 and TNIK) were also affected by EtOH treatment. Conclusions: The observed changes in protein expression highlight the involvement of oxidative stress and dysregulation of Ca2+ handling and contraction while also implicating potential novel targets in alcohol‐induced cardiotoxicity. These findings facilitate further exploration of potential mechanisms, discovery of novel biomarkers, and development of targeted therapeutics against EtOH‐induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Published
2020
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7. Proteomic Profiling Reveals Roles of Stress Response, Ca2+Transient Dysregulation, and Novel Signaling Pathways in Alcohol‐Induced Cardiotoxicity

Author

Liu, Rui, Sun, Fangxu, Forghani, Parvin, Armand, Lawrence C., Rampoldi, Antonio, Li, Dong, Wu, Ronghu, and Xu, Chunhui

Abstract

Alcohol use in pregnancy increases the risk of abnormal cardiac development, and excessive alcohol consumption in adults can induce cardiomyopathy, contractile dysfunction, and arrhythmias. Understanding molecular mechanisms underlying alcohol‐induced cardiac toxicity could provide guidance in the development of therapeutic strategies. We have performed proteomic and bioinformatic analysis to examine protein alterations globally and quantitatively in cardiomyocytes derived from human‐induced pluripotent stem cells (hiPSC‐CMs) treated with ethanol (EtOH). Proteins in both cell lysates and extracellular culture media were systematically quantitated. Treatment with EtOH caused severe detrimental effects on hiPSC‐CMs as indicated by significant cell death and deranged Ca2+handling. Treatment of hiPSC‐CMs with EtOH significantly affected proteins responsible for stress response (e.g., GPX1 and HSPs), ion channel‐related proteins (e.g. ATP1A2), myofibril structure proteins (e.g., MYL2/3), and those involved in focal adhesion and extracellular matrix (e.g., ILK and PXN). Proteins involved in the TNF receptor‐associated factor 2 signaling (e.g., CPNE1 and TNIK) were also affected by EtOH treatment. The observed changes in protein expression highlight the involvement of oxidative stress and dysregulation of Ca2+handling and contraction while also implicating potential novel targets in alcohol‐induced cardiotoxicity. These findings facilitate further exploration of potential mechanisms, discovery of novel biomarkers, and development of targeted therapeutics against EtOH‐induced cardiotoxicity. Treatment of human stem cell‐derived cardiomyocytes with ethanol results in cell death and abnormal Ca2+handling. Proteomic profiling and bioinformatic analysis reveal that ethanol treatment affects the expression of proteins involved in oxidative stress, ion channels, myofibril structure, focal adhesion, extracellular matrix and TRAF2 signaling.

Published
2020
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8. Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques

Author

Luo, Kan, primary, Liao, Hua-Xin, additional, Zhang, Ruijun, additional, Easterhoff, David, additional, Wiehe, Kevin, additional, Gurley, Thaddeus C., additional, Armand, Lawrence C., additional, Allen, Ashley A., additional, Von Holle, Tarra A., additional, Marshall, Dawn J., additional, Whitesides, John F., additional, Pritchett, Jamie, additional, Foulger, Andrew, additional, Hernandez, Giovanna, additional, Parks, Robert, additional, Lloyd, Krissey E., additional, Stolarchuk, Christina, additional, Sawant, Sheetal, additional, Peel, Jessica, additional, Yates, Nicole L., additional, Dunford, Erika, additional, Arora, Sabrina, additional, Wang, Amy, additional, Bowman, Cindy M., additional, Sutherland, Laura L., additional, Scearce, Richard M., additional, Xia, Shi-Mao, additional, Bonsignori, Mattia, additional, Pollara, Justin, additional, Edwards, R. Whitney, additional, Santra, Sampa, additional, Letvin, Norman L., additional, Tartaglia, James, additional, Francis, Donald, additional, Sinangil, Faruk, additional, Lee, Carter, additional, Kaewkungwal, Jaranit, additional, Nitayaphan, Sorachai, additional, Pitisuttithum, Punnee, additional, Rerks-ngarm, Supachai, additional, Michael, Nelson L., additional, Kim, Jerome H., additional, Alam, S. Munir, additional, Vandergrift, Nathan A., additional, Ferrari, Guido, additional, Montefiori, David C., additional, Tomaras, Georgia D., additional, Haynes, Barton F., additional, and Moody, M. Anthony, additional

Published
2016
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9. HIV-1 Vaccine-Induced C1 and V2 Env-Specific Antibodies Synergize for Increased Antiviral Activities

Author

Pollara, Justin, primary, Bonsignori, Mattia, additional, Moody, M. Anthony, additional, Liu, Pinghuang, additional, Alam, S. Munir, additional, Hwang, Kwan-Ki, additional, Gurley, Thaddeus C., additional, Kozink, Daniel M., additional, Armand, Lawrence C., additional, Marshall, Dawn J., additional, Whitesides, John F., additional, Kaewkungwal, Jaranit, additional, Nitayaphan, Sorachai, additional, Pitisuttithum, Punnee, additional, Rerks-Ngarm, Supachai, additional, Robb, Merlin L., additional, O'Connell, Robert J., additional, Kim, Jerome H., additional, Michael, Nelson L., additional, Montefiori, David C., additional, Tomaras, Georgia D., additional, Liao, Hua-Xin, additional, Haynes, Barton F., additional, and Ferrari, Guido, additional

Published
2014
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