Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Disruption of Nrf2 synergizes with high glucose to cause heightened myocardial oxidative stress and severe cardiomyopathy in diabetic mice.

Authors
He-X; Ma-Q
Source
J Diabetes Metab 2013 Sep; 4(7):002
NIOSHTIC No.
20041271
Abstract
High glucose-induced oxidative stress is a major contributing mechanism to the development of diabetic cardiomyopathy. Nrf2 is an emerging critical regulator of cellular defense against oxidative damage. The role of Nrf2 in diabetic cardiomyopathy was investigated in vivo. Streptozotocin (STZ) induced diabetes in Nrf2 knockout (KO) mice that rapidly progressed to severe conditions with high mortality within two weeks of injection; whereas, in wild type (WT) mice, diabetes was less severe with no death. Severe myocardial lesions were observed in diabetic KO mice that had high, sublethal levels of blood glucose including: (a) irregular myocardial arrangements, myofibrillar discontinuation, and cell death; (b) reduced electron density, discontinuation of myocardial fibers, and mitochondrial damage; and (c) markedly reduced contractility of the cardiomyocytes to beta-agonist stimulation. Parallel to severe cardiomyopathy, the diabetic KO hearts showed: (a) increased apoptosis as revealed by TUNEL and PARP1 cleavage assays; (b) infiltration of granulocytes and macrophages as well as fibrosis indicating robust inflammatory response; and (c) heightened oxidative stress as evidenced by increased levels of 8-hydroxydeoxyquanine, free malondialdehyde, and 3-nitrotyrosine. Increased oxidative stress in the KO hearts was attributed to decrease or loss of the basal and induced expression of Nrf2-dependent cytoprotective genes. Our findings demonstrate that loss of Nrf2 function synergizes with high glucose to cause heightened oxidative stress in the heart leading to severe diabetic cardiomyopathy.
Keywords
Laboratory-animals; Cardiovascular-function; Cardiovascular-system; Myocardial-disorders; Oxidative-processes; In-vivo-study; Mortality-rates; Blood-sugar-disorders; Cellular-function; Cell-alteration; Cell-damage; Heart; Bioassays; Fibrosis; Synergism; Cytology
Contact
Qiang Ma, NIOSH/HELD, Mailstop 3014, 1095 Willowdale Rd., Morgantown, WV 26505, USA
CODEN
JDMOAK
Publication Date
20130901
Document Type
Journal Article
Email Address
qam1@cdc.gov
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
B08142012
Issue of Publication
7
ISSN
2155-6156
NIOSH Division
HELD
Source Name
Journal of Diabetes & Metabolism
State
WV
TOP