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운동에 의한 골격근 내 PGC-1α전사 조절 기전

Mechanism for exercise induced PGC-1α transcription in skeletal muscle.

김기진|고진호|김필상|김상현
한국운동생리학회|2013.08|운동과학 (Exercise Science)|제22권 제3호|pp. 203-211|DOI 10.15857/ksep.2013.22.3.203

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참고문헌

키워드

운동ExerciseSkeletal muscleCREB골격근PGC-1αp38 MAPKATF2β-adrenegic receptor

초록

본 연구는 PGC-1α의 promoter에 존재하는 CRE 서열에 결합하여 PGC-1α의 전사를 유도하는 ATF2와 CREB의 활성화를 중심으로 운동 시 골격근 내 PGC-1α의 전사가 어떻게 이루어지는지 알아보았다. 이를 위해 luciferase reporter system을 이용하여 골격근 내 ATF2와 CREB의 인산화 그리고 PGC-1α의 전사를 확인하기 위해 생쥐의 골격근세포에 clenbuterol(β2-adrenergic agonist)과 anisomycin(p38 MAPK activator)을 처치하였다. 또한 흰쥐 12마리를 무작위로 두 그룹(Sedentary와 Exercise)으로 분류한 후 운동 그룹은 30분간 수영(2 % weight/body weight, 30 min)을 실시하였으며, 운동직후 CREB과 ATF2의 인산화 정도를 확인하기 위해 골격근을 적출하였다. 그 결과 clenbuterol 처치는 CREB의 인산화를 증가시켰으며, anisomycin의 처치는 ATF2의 인산화를 증가시켰다. 그러나 운동에 의해서는 ATF2만 인산화가 증가하였다. 그리고 PGC-1α의 전사 또한 ATF2의 인산화에 의해서만 유도되었으며, DN-ATF2에 의해서는 PGC-1α의 전사가 완벽히 억제되었다. 이러한 결과는 운동 시 골격근 내 p38 MAPK 기전의 활성에 의한 ATF2 인산화가 PGC-1α의 전사를 유도함을 나타낸다.

Abstract

This study determines which transcriptional factors, activating transcription factor 2 (ATF2) and/or cAMP responsive element binding protein (CREB), bind to and activate cAMP response element (CRE) transcriptional binding site of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) promoter during exercise. C2C12 cells were treated clenbuterol(β2-adrenergic agonist) and anisomycin (p38 MAPK activator) to determine weather p-CREB and/or p-ATF2 can activate PGC-1α promoter transcriptional activities using luciferase reporter system. Twelve rats were randomly assigned into 2 groups (Sedentary and Exercise). Exercise group was trained by using a 30min swimming with tail load equivalent to 2 % of animal's own body weight. Muscle samples were harvested immediately after exercise. Clenbuterol and anisomycin increased phosphorylation of CREB and ATF2 respectively in C2C12. The ATF2 phosphorylation was increased in the exercise group compared with sedentary group, but CREB phosphorylation was not changed after exercise. PGC-1α transcription activities were enhanced by ATF2 activation, but not in CREB activated condition. Induction of DN-ATF2 completely blocked PGC-1α promoter activity by p-ATF2. These findings suggest that ATF2 phosphorylation by p38 MAPK system induce PGC-1α transcription in exercised muscle.

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