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Exp Cell Res. 2017 Mar 15;352(2):273-280. doi: 10.1016/j.yexcr.2017.02.015. Epub 2017 Feb 12.

Sulfiredoxin involved in the protection of peroxiredoxins against hyperoxidation in the early hyperglycaemia.

Author information

1
Department of Pathophysiology, Harbin Medical University, Harbin 150081, China.
2
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
3
Department of Blood transfusion, Jiamusi Central Hospital, Jiamusi 154000, China.
4
Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. Electronic address: xzhong1111@163.com.
5
Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. Electronic address: drlihong1971@163.com.

Abstract

As a direct consequence of hyperglycaemia, the excessive generation of ROS is central to the pathogenesis of diabetic cardiomyopathy. We hypothesize that stimulation of high glucose (HG) results in an increased sulfiredoxin (Srx) expression, which regulates ROS signaling through reducing the hyperoxidized peroxiredoxins (Prxs). We show that hyperoxidized Prxs were initially reduced in the preliminary stage but then dramatically increased in advanced stage and these changes corresponded to a significant increase of Srx expression in the heart of diabetic rats. These time-dependent changes were also confirmed in neonatal cardiomyocytes and H9c2 cells treated with HG. Moreover, the reduction rate of hyperoxidized Prxs was greatly improved in the HG 24h group, which had an elevated expression of Srx. Our data also show that HG-induced AP1 activation and Srx expression were almost abolished by JNK inhibitor and N-acetylcysteine (NAC). In addition, siRNA-Srx suppressed HG-induced ANP and β-MHC gene expression. These observations suggest that activation of AP1 induced by HG is important for the expression of Srx and the reduction of hyperoxidized Prxs in cardiomyocytes. This Srx induction maybe is the pivotal compensatory protection mechanism against oxidative stress in diabetes or hyperglycaemia. Most interestingly, hyperoxidized Prxs/Srx pathway may be involved in the cardiac hypertrophy signaling of diabetes.

KEYWORDS:

Cardiomyocyte; High glucose; Hyperoxidation; Peroxiredoxin; Sulfiredoxin

PMID:
28202395
DOI:
10.1016/j.yexcr.2017.02.015
[Indexed for MEDLINE]

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