title: Short-Term Hypoxia Reverses Ox-LDL-Induced CD36 and GLUT4 Switching Metabolic Pathways in H9c2 Cardiomyoblast Cells.
abstract: High levels of circulating low-density lipoproteins (LDL, plasma proteins that carry cholesterol and triglycerides) are associated with type 2 diabetes, arteriosclerosis, obesity, and hyperlipidemia. In the heart, the accumulation of oxidized low-density lipoprotein (Ox-LDL) has been proposed to play a role in the development of cardiovascular disease. We obtain cholesterol from animals and animal-derived foods such as milk, eggs, and cheese. In previous studies, the ratio of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) was shown to be important for our health. High levels of LDL cholesterol lead to atherosclerosis, increasing the risk of heart attack and ischemic stroke. In this study, we utilized Ox-LDL-treated H9c2 cardiomyoblast cells as a simulated hyperlipidemia model. CD36 metabolism pathway proteins (phospho-Akt, SIRT1, PGC1α, PPARα, CPT1β, and CD36) increased at low doses of Ox-LDL. However, high doses (150 and 200 mg/dL) of Ox-LDL reduced the levels of these proteins. Interestingly, expression of GLUT4 metabolism pathway proteins (phospho-PKCζ) were reduced at low doses, while the expression of phospho-AMPK, phospho-PI3K, phospho-PKCζ, GLUT4, and PDH proteins increased at high doses. Ox-LDL acute treatment induces apoptosis in cardiomyocytes as evidenced by apoptotic nuclei apparition, caspase-3 activation, and cytochrome c release from mitochondria. In our results, Ox-LDL induced lipotoxicity in cardiomyocytes, and subsequent exposure to short-term hypoxia or reversed the Ox-LDL-induced metabolic imbalance. The same result was obtained with the pharmacological activation of SIRT1 by resveratrol and si-PKCζ. The mechanism of metabolic switching during Ox-LDL lipotoxicity seems to be mediated by SIRT1 and PKC ζ. J. Cell. Biochem. 118: 3785-3795, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Ph.D. Program for Aging, China Medical University, Taichung, Taiwan.|Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Yeh-Peng
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.|Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Rathinasamy
authors.initials: R
authors.lastname: Baskaran
authors.affiliation: Mackay Medicine, Nursing and Management College, Taipei, Taiwan.|Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wen
authors.affiliation: Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan.
authors.forename: Chia-Yao
authors.initials: CY
authors.lastname: Shen
authors.affiliation: Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan.
authors.forename: Cecilia-Hsuan
authors.initials: CH
authors.lastname: Day
authors.affiliation: Chinese Medicine Department, China Medical University Beigang Hospital, Taichung, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore, 641046, India.
authors.forename: Viswanadha
authors.identifier: 0000-0001-9154-027X
authors.initials: V
authors.lastname: Vijaya Padma
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.identifier: 0000-0003-2347-0411
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006949:Hyperlipidemias / Q000378:metabolism* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D032386:Myoblasts, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats
chemical_list: D018955:CD36 Antigens; C008132:Cd36 protein, rat; D051275:Glucose Transporter Type 4; D008077:Lipoproteins, LDL; C495694:Slc2a4 protein, rat; C099252:oxidized low density lipoprotein
keywords: CARDIO-MYOBLAST CELLS; CONTRACTION PATHWAY; FATTY ACID METABOLISM; GLUCOSE METABOLISM; INSULIN SIGNALING PATHWAY; OXIDIZED LOW-DENSITY LIPOPROTEIN