Open AccessDeficiency of insulin‐like growth factor 1 reduces vulnerability to chronic alcohol intake‐induced cardiomyocyte mechanical dysfunction: role of AMPK
Author(s) -
Ge Wei,
Li Qun,
Turdi Subat,
Wang XiaoMing,
Ren Jun
Publication year - 2011
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.1582-4934.2010.01158.x
Subject(s) - endocrinology , medicine , ampk , aldh2 , alcoholic cardiomyopathy , intracellular , insulin like growth factor , amp activated protein kinase , protein kinase a , biology , aldehyde dehydrogenase , kinase , growth factor , heart failure , biochemistry , receptor , cardiomyopathy , enzyme
Circulating insulin‐like growth factor I (IGF‐1) levels are closely associated with cardiac performance although the role of IGF‐1 in alcoholic cardiac dysfunction is unknown. This study was designed to evaluate the impact of severe liver IGF‐1 deficiency (LID) on chronic alcohol‐induced cardiomyocyte contractile and intracellular Ca 2+ dysfunction. Adult male C57 and LID mice were placed on a 4% alcohol diet for 15 weeks. Cardiomyocyte contractile and intracellular Ca 2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time‐to‐relengthening (TR 90 ), change in fura‐fluorescence intensity (ΔFFI) and intracellular Ca 2+ decay. Levels of apoptotic regulators caspase‐3, Bcl‐2 and c‐Jun NH2‐terminal kinase (JNK), the ethanol metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), as well as the cellular fuel gauge AMP‐activated protein kinase (AMPK) were evaluated. Chronic alcohol intake enlarged myocyte cross‐sectional area, reduced PS, ± dL/dt and ΔFFI as well as prolonged TR 90 and intracellular Ca 2+ decay, the effect of which was greatly attenuated by IGF‐1 deficiency. The beneficial effect of LID against alcoholic cardiac mechanical defect was ablated by IGF‐1 replenishment. Alcohol intake increased caspase‐3 activity/expression although it down‐regulated Bcl‐2, ALDH2 and pAMPK without affecting JNK and AMPK. IGF‐1 deficiency attenuated alcoholism‐induced responses in all these proteins with the exception of Bcl‐2. In addition, the AMPK agonist 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside abrogated short‐term ethanol incubation‐elicited cardiac mechanical dysfunction. Taken together, these data suggested that IGF‐1 deficiency may reduce the sensitivity to ethanol‐induced myocardial mechanical dysfunction. Our data further depicted a likely role of Caspase‐3, ALDH2 and AMPK activation in IGF‐1 deficiency induced ‘desensitization’ of alcoholic cardiomyopathy.