title: Hypoxia Augments Increased HIF-1α and Reduced Survival Protein p-Akt in Gelsolin (GSN)-Dependent Cardiomyoblast Cell Apoptosis.
abstract: Cytoskeleton filaments play an important role in cellular functions such as maintaining cell shape, cell motility, intracellular transport, and cell division. Actin-binding proteins (ABPs) have numerous functions including regulation of actin filament nucleation, elongation, severing, capping, cross linking, and actin monomer sequestration. Gelsolin (GSN) is one of the actin-binding proteins. Gelsolin (GSN) is one of the actin-binding proteins that regulate cell morphology, differentiation, movement, and apoptosis. GSN also regulates cell morphology, differentiation, movement, and apoptosis. In this study, we have used H9c2 cardiomyoblast cell and H9c2-GSN stable clones to understand the roles and mechanisms of GSN overexpression in hypoxia-induced cardiomyoblast cell death. The data show that hypoxia or GSN overexpression induces HIF-1α expression and reduces the expression of survival markers p-Akt and Bcl-2 in H9c2 cardiomyoblast cells. Under hypoxic conditions, GSN overexpression further reduces p-Akt expression and elevates total as well as cleaved GSN levels and HIF-1α levels. In addition, GSN overexpression enhances apoptosis in cardiomyoblasts under hypoxia. Hypoxic challenge further induced activated caspase-3 and cell death that was attenuated after GSN knock down, which implies that GSN is a critical therapeutic target against hypoxia-induced cardiomyoblast cell death.
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.|Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.forename: Wei-Syun
authors.lastname: Hu
authors.affiliation: Graduate Institute of Basic Medical Science, School of Chinese Medicine, China Medical University and Hospital, 91 Hsueh-Shih Road 404, Taichung, Taiwan, ROC.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Ting
authors.affiliation: Department of Nursing, MeiHo University, Pingtung, Taiwan.
authors.forename: Chia-Yao
authors.initials: CY
authors.lastname: Shen
authors.affiliation: Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan County, Taiwan.
authors.forename: Li-Chin
authors.initials: LC
authors.lastname: Chung
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan.
authors.forename: Chuan-Chou
authors.initials: CC
authors.lastname: Tu
authors.affiliation: Department of Health, Tsao-Tun Psychiatric Center, Executive Yuan, Nantou, 54249, Taiwan.
authors.forename: Sheng-Huang
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Department of Nursing, MeiHo University, Pingtung, Taiwan.
authors.forename: Cecilia-Hsuan
authors.initials: CH
authors.lastname: Day
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Basic Medical Science, School of Chinese Medicine, China Medical University and Hospital, 91 Hsueh-Shih Road 404, Taichung, Taiwan, ROC. cyhuang@mail.cmu.edu.tw.|School of Chinese Medicine, China Medical University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D018260:Gelsolin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D010750:Phosphoproteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats
chemical_list: D015415:Biomarkers; D018260:Gelsolin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: Cardiomyoblast cell apoptosis; Gelsolin; HIF-1α; Hypoxia; p-Akt