Nrf2 Is Critical in Defense Against High Glucose-Induced Oxidative Damage in Cardiomyocytes

Details

• Personal Author:
  Cai L ; He X ; Kan H ; Ma Q
• Description:
  Exposure to high levels of glucose induces the production of reactive oxygen species (ROS) in cardiomyocytes that may contribute to the development of cardiomyopathy in diabetes. Nuclear factor erythroid 2-related factor 2 (Nrf2) controls the antioxidant response element (ARE)-dependent gene regulation in response to oxidative stress. The role of Nrf2 in defense against high glucose-induced oxidative damage in cardiomyocytes was investigated. Glucose at high concentrations induced ROS production in both primary neonatal and adult cardiomyocytes from the Nrf2 wild type (WT) mouse heart, whereas, in Nrf2 knockout (KO) cells, ROS was significantly higher under basal conditions and high glucose markedly further increased ROS production in concentration and time-dependent manners. Concomitantly, high glucose induced significantly higher levels of apoptosis at lower concentrations and in shorter time in Nrf2 KO cells than in WT cells. Primary adult cardiomyocytes from control and diabetic mice also showed dependence on Nrf2 function for isoproterenol-stimulated contraction. Additionally, cardiomyocytes from Nrf2 KO mice exhibited increased sensitivity to 3-nitropropionic acid, an inhibitor of mitochondrial respiratory complex II, for both ROS production and apoptosis compared with Nrf2 WT cells, further emphasizing the role of Nrf2 in ROS defense in the cells. Mechanistically, Nrf2 was shown to mediate the basal expression and induction of ARE-controlled cytoprotective genes, Nqo1 and Ho1, at both mRNA and protein levels in cardiomyocytes, as both the basal and inducible expressions of the genes were lost in Nrf2 KO cells or largely reduced by Nrf2 SiRNA. The findings, for the first time, established Nrf2 as a critical regulator of defense against ROS in normal and diabetic hearts. [Description provided by NIOSH]
• Subjects:
  Antioxidants Cardiovascular Diseases Cardiovascular System Genetics Occupational Health Safety
• Keywords:
  Antioxidant Antioxidation Author Keywords: Nrf2 Cardiac-function Cardiovascular-system-disease Cardiovascular-system-disorders Cell-biology Cell-function Cellular-reactions Diabetic Cardiomyopathy Genes Genetic-factors Glucose Myocardial-disorders Myocardium Oxidative Stress Reactive Oxygen Species

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• ISSN:
  0022-2828
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Kentucky ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  47-58
• Volume:
  46
• Issue:
  1
• NIOSHTIC Number:
  nn:20034762
• Citation:
  J Mol Cell Cardiol 2009 Jan; 46(1):47-58
• Contact Point Address:
  Qiang Ma, National Institute for Occupational Safety and Health, CDC, Receptor Biology Laboratory, TMBB, HELD, MS 3014, 1095 Willowdale Road, Morgantown, WV 26505; Lu Cai, Dept. of Medicine, Shool of Medicine, Univ. of Louisville, Louistille, KY 40202
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Molecular and Cellular Cardiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cb1732b77c9fa3a5eb0ce205a759586ea9117e2740388c3ef004afd12983dd6a0610f965103a7045df424447d783d3b4cf4032ceab1bd49b0d88f4b9c336869b
• Download URL:
  https://stacks.cdc.gov/view/cdc/186855/cdc_186855_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]