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Exerc Sci > Volume 20(3); 2011 > Article
Exercise Science 2011;20(3): 205-214. doi: https://doi.org/10.15857/ksep.2011.20.3.205
SAMS-GFP 펩티드에 의한 AMP-activated protein kinase 기능 차단이 골격근 내 당 수송에 미치는 영향
김상현1, Kawuhiko Higashida2, 김기진1
1계명대학교
2워싱턴대학
Inhibition of AMP-activated protein kinase by SAMS-GFP peptide on glucose transport in skeletal muscle.
ABSTRACT
Glucose transport in skeletal muscle during exercise is mainly accomplished by AMP-activated protein kinase (AMPK) and Ca2+/calmodulin-dependent protein kinase (CaMK) signaling pathways. AMPK exists as heterotrimeric αβγ complexes, while the catalytic subunit has two isoforms (α1 and α2) with different tissue distributions. AMPK complexes containing the α2, rather than the α1 isoform, have a greater dependency on AMP both in direct allosteric activation and in covalent activation by the upstream kinase, LKB1. Therefore, AMPKα2 is thought to be the main isoform in skeletal muscle. Although in AMPKα2 KO mice AMPKα2 activity is abolished, AMPKα1 activity is compensatorily increased. To overcome these obstacles, we designed a SAMS-GFP pseudo peptide vector to block the function of both AMPKα1 and AMPKα2 in skeletal muscle. SAMS-GFP peptide overexpression in rat epitrochlearis muscle was accomplished by using an electric pulse-mediated gene transfer technique. Induction of AMPK pseudo peptide, SAMS-GFP completely blocked AICAR stimulated glucose transport activity. Hypoxia and muscle contraction induce an increase of glucose transport by 6.5 and 4.4 times, respectively. But, this hypoxia- and contraction- induced increase of glucose transport is decreased about 50% by SAMS-GFP. SAMS-GFP peptide overexpression did not change muscle GLUT4 content. These findings suggestthat AMPK with CaMK signaling pathways play a key role on glucose transport by contraction in skeletal muscle. And SAMS-GFP inhibitory peptide completely blocked the function of AMPKα1 and AMPKα2, contrary to AMPKα2 KO mice, in which only α2 is blocked.
Key words: AMPK, glucose transport, muscle contraction, Hypoxia SAMS peptide
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