Open AccessAcute hyperglycaemia enhances oxidative stress and aggravates myocardial ischaemia/reperfusion injury: role of thioredoxin‐interacting protein
Author(s) -
Su Hui,
Ji Lele,
Xing Wenjuan,
Zhang Wei,
Zhou Heping,
Qian Xinhong,
Wang Xiaoming,
Gao Feng,
Sun Xin,
Zhang Haifeng
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01661.x
Subject(s) - txnip , thioredoxin interacting protein , oxidative stress , thioredoxin , medicine , reperfusion injury , apoptosis , myocardial infarction , ischemia , protein kinase b , endocrinology , p38 mitogen activated protein kinases , chemistry , pharmacology , mapk/erk pathway , signal transduction , biochemistry
Hyperglycaemia during acute myocardial infarction is common and associated with increased mortality. Thioredoxin‐interacting protein (Txnip) is a modulator of cellular redox state and contributes to cell apoptosis. This study aimed to investigate whether or not hyperglycaemia enhances Txnip expression in myocardial ischaemia/reperfusion ( MI /R) and consequently exacerbates MI /R injury. Rats were subjected to 30 min. of left coronary artery ligation followed by 4 hrs of reperfusion and treated with saline or high glucose (HG, 500 g/l, 4 ml/kg/h intravenously). In vitro study was performed on cultured rat cardiomyocytes subjected to simulated ischaemia/reperfusion (SI/R) and incubated with HG (25 mM) or normal glucose (5.6 mM) medium. In vivo HG infusion during MI /R significantly impaired cardiac function, aggravated myocardial injury and increased cardiac oxidative stress. Meanwhile, Txnip expression was enhanced whereas thioredoxin activity was inhibited following HG treatment in ischaemia/reperfusion (I/R) hearts. In addition, HG activated p38 MAPK and inhibited Akt in I/R hearts. In cultured cardiomyocytes subjected to SI /R, HG incubation stimulated Txnip expression and reduced thioredoxin activity. Overexpression of Txnip enhanced HG ‐induced superoxide generation and aggravated cardiomyocyte apoptosis, whereas Txnip RNA i significantly blunted the deleterious effects of HG . Moreover, inhibition of p38 MAPK or activation of Akt markedly blocked HG ‐induced Txnip expression in I/R cardiomyocytes. Most importantly, intramyocardial injection of Txnip si RNA markedly decreased Txnip expression and alleviated MI /R injury in HG ‐treated rats. Hyperglycaemia enhances myocardial Txnip expression, possibly through reciprocally modulating p38 MAPK and Akt activation, leading to aggravated oxidative stress and subsequently, amplification of cardiac injury following MI /R.