Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation.

Abstract

This study was to investigate whether sulforaphane (SFN) can prevent diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by multiple intraperitoneal injections with low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without SFN at 0.5mg/kg daily in five days of each week for 3 months and then kept until 6 months. At 3 and 6 months of diabetes, blood pressure and cardiac function were assessed. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot, real-time qPCR, and histopathological examination. SFN significantly prevented diabetes-induced high blood pressure and cardiac dysfunction at both 3 and 6 months, and also prevented diabetes-induced cardiac hypertrophy (increased the ratio of heart weight to tibia length and the expression of atrial natriuretic peptide mRNA and protein) and fibrosis (increased the accumulation of collagen and expression of connective tissue growth factor and tissue growth factor-β). SFN also almost completely prevented diabetes-induced cardiac oxidative damage (increased accumulation of 3-nitrotyrosine and 4-hydroxynonenal) and inflammation (increased tumor necrotic factor-α and plasminogen activator inhibitor 1 expression). SFN up-regulated NFE2-related factor 2 (Nrf2) expression and transcription activity that was reflected by increased Nrf2 nuclear accumulation and phosphorylation as well as the mRNA and protein expression of Nrf2 downstream antioxidants. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the SFN's prevention of high glucose-induced fibrotic response. These results suggest that diabetes-induced cardiomyopathy can be prevented by SFN, which was associated with the up-regulated Nrf2 expression and transcription function.

• Authors: Yang Bai, Wenpeng Cui, Ying Xin, Xiao Miao, Michelle T Barati, Chi Zhang, Qiang Chen, Yi Tan, Taixing Cui, Yang Zheng, Lu Cai
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 57 Pg. 82-95 (Apr 2013) ISSN: 1095-8584 [Electronic] England
• PMID: 23353773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• CCN2 protein, mouse
• Isothiocyanates
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Serpin E2
• Serpine2 protein, mouse
• Sulfoxides
• Thiocyanates
• Connective Tissue Growth Factor
• Catalase
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Sod1 protein, mouse
• Sod1 protein, rat
• Superoxide Dismutase
• Superoxide Dismutase-1
• sulforaphane

Topics

• Animals
• Catalase (metabolism)
• Cell Line
• Connective Tissue Growth Factor (genetics, metabolism)
• Diabetes Mellitus, Experimental (complications, drug therapy, metabolism)
• Diabetic Cardiomyopathies (metabolism, physiopathology, prevention & control)
• Drug Evaluation, Preclinical
• Fibrosis
• Heme Oxygenase-1 (metabolism)
• Hypertrophy, Left Ventricular (etiology, metabolism, prevention & control)
• Isothiocyanates
• Lipid Peroxidation
• Male
• Membrane Proteins (metabolism)
• Mice
• NF-E2-Related Factor 2 (genetics, metabolism)
• Oxidative Stress
• Rats
• Serpin E2 (metabolism)
• Sulfoxides
• Superoxide Dismutase (metabolism)
• Superoxide Dismutase-1
• Thiocyanates (pharmacology, therapeutic use)
• Transcription, Genetic
• Transcriptional Activation
• Up-Regulation