지구성 운동 시 NT-PGC-1α가 흰쥐 골격근 내 미토콘드리아 생합성에 미치는 영향
Role of NT-PGC-1α on endurance exercise induced mitochondiral biogenesis in rat skeletal muscle.
2
조회
0
다운로드
5
인용
0
참고문헌
키워드
초록
NT-PGC-1α는 갈색지방조직에서 PGC-1α와 유사한 생물학적 작용을 하는 것으로 알려져 있으나, 골격근에서는 아직 어떠한 생물학적 효과를 나타내는지 알려지지 않았다. 이에 본 연구의 목적은 PGC-1α의 짧은 형태인 NT-PGC-1α가 골격근 내 미토콘드리아 생합성에 어떠한 영향을 미치는가를 알아보는 것이다. 지구성 운동에 따른 골격근 내 PGC-1α, NT-PGC-1α 그리고 미토콘드리아 생합성 정도를 알아보기 위해 18마리의 흰쥐를 각각 6마리씩 3그룹(sedentary; Sed, 1 day exercise; 1d Ex, 3 day exercise; 3d Ex)으로 분류한 다음 수영을 실시(6 h/day)하였다. 골격근은 마지막 운동훈련 18시간 후 적출하였다. 그 결과 지구성 운동에 따른 골격근 내 PGC-1α의 발현은 1일 운동 후에는 Sed 그룹에 비해 유의하게 증가하였으나, 3일 운동 후에는 1일 운동에 의해 증가된 정도가 Sed 그룹 수준으로 감소하였다. NT-PGC-1α는 1일 운동 후에는 Sed 그룹과 비교해 차이가 없었으나, 3일 운동 후 유의하게 증가하였다. 그리고 지구성 운동에 따른 골격근 내 COXⅠ과 NADH-UO는 1일과 3일 트레이닝 후 모두 유의하게 증가하였다. 또한 NT-PGC-1α가 미토콘드리아 생합성에 어떠한 영향을 미치는지 알아보기 위해 C2C12 골격근 세포에 NT-PGC-1α adenovirus를 처치하여 NT-PGC-1α를 과발현 시킨 후 미토콘드리아 효소의 발현정도를 분석한 결과 미토콘드리아 효소인 cytochrome c, COXⅠ, ATP synthase, citrate synthase 모두 유의하게 증가하였다. 이러한 결과를 종합해 볼 때, PGC-1α는 미토콘드리아 생합성 초기에 관여하고, NT-PGC-1α는 PGC-1α에 의해 증가된 미토콘드리아 생합성을 계속 유지하거나 약간 더 증가시키는데 중요한 역할을 할 것이다.
Abstract
N-truncated peroxisome proliferator-activated receptor γ coactivator-1α splice variant (NT-PGC-1α) has similar biological effects to peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) in brown adipose tissue. But, the effect of NT-PGC-1α on mitochondrial biogenesis in skeletal muscles has not been clearly identified. The purpose of this study is to verify that NT-PGC1 induce the mitocondrial biogenesis in skeletal muscle. Eighteen rats were randomly assigned into 3 groups (Sedentary, Sed; 1 day exercise, 1d Ex; 3 day exercise, 3d Ex). Exercise groups were trained by using a 6 h/day swimming program. Muscle samples for PGC-1α, NT-PGC-1α and mitochondrial enzymes were harvested 18 hours after the last bout of exercise. The expression of PGC-1α was increased in the 1d Ex compared with Sed group, but 3d Ex group was not changed compared with Sed group. NT-PGC-1α was increased in the 3d Ex group from the Sed group. The expressions of cytochrome oxidase subunit I (COXⅠ)and NADH-ubiquinone oxidoreductase (NADH-UO) were increased in the 1d Ex and 3d Ex group from the Sed group. Three day overexpressed NT-PGC-1α C2C12 myotubes were harvested for mitochondrial enzymes. The expressions of mitochondrial enzymes, cytochrome c, COXⅠ, ATP synthase and citrate synthase were increased in the NT-PGC-1α overexpressed C2C12 from the Sed group. These findings suggest that PGC-1α protein is responsible for initial increase in mitochondrial biogenesis. While NT-PGC-1α is important for chronic exercise induced increase in mitochondrial proteins.
참고문헌 (38)
- Baar, K., "Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1", FASEB J, 16(14), pp.1879~1886 (2002)
- Booth, F. W., "Cytochrome c turnover in rat skeletal muscles", J. Biol. Chem, 25(2), pp.416~419 (1977)
- Chang, J. S., "NT-PGC-1α protein is sufficient to link β3-adrenergic receptor activation to transcriptional and physiological components of adaptive thermogenesis", J. Biol.Chem, 287(12), pp.9100~9111 (2012)
- Chang, J. S., "Regulation of NT-PGC-1alpha subcellular localization and function by protein kinase A-dependent modulation of nuclear export by CRM1", J. Biol. Chem, 285(23), pp.18039~18050 (2010)
- Cyert, M. S., "Regulation of lnuclear localization during signaling", J. Biol. Chem, 276(24), pp.20805~20808 (2001)
- Fan. M., "Suppression of lmitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha:modulation by p38 MAPK", Genes Dev., 18(3), pp.278~289 (2004)
- Garcia-Roves, P. M., "Prevention of glycogen supercompensation prolongs the increase in muscle GLUT4 after exercise", Am. J. Physiol. Endocrinol. Metab, 285(4), pp.729~736 (2003)
- Goto, M., "cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats", Biochem Bophys Res Commun, 274(2), pp.350~353 (2000)
- Handschin, C., "Peroxisome proliferator acivated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism", Endocr. Rev, 27, pp.728~735 (2006)
- 김상현, "Normal adaptations to exercise despite protection against oxidative stress", AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 301(5), pp.779~784, AMER PHYSIOLOGICAL SOC
- Holloszy, J. O., "Biochemical adaptations in muscle. Effects of exercise on mitochondrial O2 uptake and respiratory enzyme activity in skeletal muscle", J. Biol. Chem, 242, pp.2278~2282 (1967)
- Holloszy, J. O., "Mitochondrial citric acid cycle and related enzymes:Adaptive response to exercise", Biochem. Biophys. Res. Commun, 40, pp.1368~1373 (1970)
- Holloszy, J. O., "Regulation by exercise of skeletal muscle content of mitochondria and GLUT4", J. Physiol. Pharmacol, 7, pp.5~18 (2008)
- Hoppeler, H., "The ultrastructure of normal hman skeletal musscle. A morphometric analysis on untrained men, women and well-trained orienteers", Pflugers Arch., 344, pp.217~232 (1973)
- Ikeda, S., "Muscle type-specific response of PGC-1 alpha and oxidative enzymes during voluntary wheel running in mouse skeletal muscle", Acta Physiol(Oxf), 188(3-4), pp.217~223 (2006)
- Kiraly, M. A., "Attenuation of type2 diabetes mellitus in the male Zucker diabetic fatty rat:the effects of stress and non-volitional exercise", Metabolism, 56, pp.732~744 (2007)
- Kraft, C., "Control of lmitochondrial biogenesis during myogenesis", Am. J. Physiol. Cell Physiol, 290, pp.1119~1127 (2006)
- Leick, L., "PGC-1alpha is not mandatory for exercise and training-induced adaptive gene responses in mouse skeletal muscle", A. J. Physiol. Endo. Metab, 294, pp.463~474 (2008)
- Lowry, O. H., "Protein measurement with the Folin phenol reagent", J. Biol. Chem, 193((1), pp.265~275 (1951)
- Mole, P. A., "Adaptation of muscle to exercise. Increase in levels of palmityl CoA synthetase, and in the capacity to oxidize fatty acids", J. Clin, Invest, 47, pp.461~467 (1971)
- Monsalve, M., "Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1", Mol. Cell, 6(2), pp.307~316 (2000)
- Olesen, J., "PGC-1alpha-mediated adaptations in skeletal muscle", Pflugers Arch, 460, pp.153~162 (2010)
- Olson, B. L., "SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis", Genes Dev., 22(2), pp.252~264 (2008)
- Oscai, L.B, "Biochemical adaptations in muscle. II. Response of mitochondrial adenosine triphosphatase, creatine phosphokinase, and adenylate kinase activities in skeletal muscle to exercise", J. Biol. Chem, 246(22), pp.6968~6972 (1971)
- Ploug, T. B., "Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle", Am. J. Physiol. Endocrinol. Metab, 259(2), pp.778~786 (1990)
- Puigserver, P, "Peroxisome proliferator activated receptor-gamma coactivator 1 alpha (PGC-1alpha):transcriptional coactivator and metabolic regulator", Endocr. Rev, 24(1), pp.78~90 (2003)
- Puigserver, P., "Activation of PPARgamma coactivator-1 through transcription factor docking", Science, 286(5443), pp.1368~1371 (1999)
- Puigserver, P., "Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1", Mol. Cell, 28(5), pp.971~982 (2001)
- Sano, M., "Intramolecular control of protein stability, subnuclear compartmentalization, and coactivator function of peroxisome proliferator-activated receptor gamma coactivator 1alpha", Biol. Chem, 252(35), pp.25970~25980 (2007)
- Scarpulla, R. C., "Transcriptional paradigms in mammalian mitochonkrial biogenesis and function", Physiol. Rev, 88(2), pp.611~638 (2008)
- Terada, S, "Effects of acute bouts of urnning and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle", Am. J. Physiol. Endocrinol. Metab, 286(2), pp.208~216 (2004)
- Terada, S., "Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle", Biochem. Biophys. Res. Commun, 296, pp.350~354 (2002)
- Vega, R. B., "The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol", Cell Biol, 20(5), pp.1868~1876 (2000)
- Wang, L., "Resistance exercise enhances the molecular signaling of lmitochondrial biogenesis induced by endurance exercise in human skeletal muscle", J. Appl. Physiol, 111(5), pp.1335~1344 (2011)
- Wende, A. R., "PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism", Mol. Cell Biol, 25, pp.10684~10694 (2005)
- Wu, H., "Regulation of mitochondrial biogenesis in skeletal muscle by CaMK", Science, 296(5566), pp.349~352 (2002)
- Wu, Z., "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1", Cell, 98(1), pp.115~124 (1999)
- Zhang, Y., "Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1alpha. J. Biol", J. Biol. Chem, 284(47), pp.32813~32826 (2009)