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AMP‐kinase prevents oxidative stress‐induced mitochondrial dysfunction through regulation of protein acetylation in cardiomyocytes
Author(s) -
BarretoTorres Giselle A.,
Javadov Sabzali
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.682.6
Subject(s) - ampk , oxidative stress , acetylation , protein kinase a , chemistry , mitochondrion , oxidative phosphorylation , amp activated protein kinase , dephosphorylation , phosphorylation , reactive oxygen species , hydrogen peroxide , kinase , microbiology and biotechnology , biochemistry , biology , phosphatase , gene
Activation of AMP‐kinase (AMPK) has been shown to exert cardioprotective effects against oxidative stress however molecular mechanisms underlying these effects remain elusive. In this study, we examined whether the beneficial effects of AMPK activation by metformin (Met) can be mediated through the acetylation of mitochondrial proteins. H9c2 cardioblast cells were divided into the following groups: 1) Control: no treatment; 2) H 2 O 2 : cells treated for 1 h with 100 μM H 2 O 2 ; 3) Met: cells treated for 1 h with 10 mM Met; 4) Met+H 2 O 2 : cells pre‐treated with 10 mM Met for 1 h followed by 1 h treatment with 100 μM H 2 O 2 . Hydrogen peroxide reduced the P‐AMPK level by 32% ( P <0.05) while Met increased phosphorylation of AMPK by 45% ( P <0.05) compared to control, when both agents were used individually. Dephosphorylation of AMPK induced by oxidative stress was associated with mitochondrial dysfunction (loss of Δψ m ), ROS accumulation, and increased protein acetylation. Pre‐treatment with Met prevented H 2 O 2 ‐induced inactivation of AMPK, enhanced Δψ m , and reduced ROS production. The protective effects of Met against oxidative stress were associated with regulation of protein acetylation in mitochondria. Thus, our data demonstrates that the activation of AMPK has protective effects against oxidative stress in cultured cardiomyocytes due to the normalization of acetylation of proteins. Supported by NHLBI NIH, and APS.