PPARδ가 생쥐 골격근의 미토콘드리아 생합성에 미치는 영향
The Role of PPARδ on Mitochondrial Biogenesis of Mouse Skeletal Muscle
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본 연구는 골격근에 PPARδ의 과발현이 미토콘드리아 효소의 발현에 어떠한 영향을 미치는지 확인하는 것이다. 전기자극 유전자 전이기법을 이용하여 생쥐의 골격근에 PPARδ의 과발현을 유도하였으며, PGC-1α가 증가하기 전과 증가된 시점에서 전자전달계 효소인 NADH dehydrogenase(NADH), cytochrome c oxidase subunit Ⅳ(COXⅣ) 및 succinate-ubiquinone oxidoreductase(SUO)와 구연산회로의 효소인 citrate synthase(CS)의 발현을 분석하였다. 생쥐의 골격근에 PPARδ가 2주 또는 4주간 과발현된 근육은 PPARδ가 대조군보다 각각 2.1배 2.8배 증가하였다. PPARδ가 2주간 과발현된 근육은 PGC-1α, COXⅣ, CS가 대조군과 차이가 없는 것으로 나타났으나, NADH와 SUO는 대조군보다 각각 1.5배 2.4배 증가하였다. PPARδ가 4주간 과발현된 근육은 PGC-1α, COXⅣ, CS, NADH 그리고 SUO가 대조군보다 각각 1.6배, 2.1배, 1.8배, 2배 그리고 2.5배 증가하였다. 본 연구는 PPARδ가 PGC-1α의 단백질 발현을 증가시키거나 또는 다른 기전을 통하여 미토콘드리아 효소의 발현을 증가시킬 수 있음을 증명하였다.
Abstract
The purpose of this study was to evaluate the role of PGC-1α and PPARδ on the mitochondrial biogenesis in mouse skeletal muscle. PPARδ overexpression in mouse skeletal muscle was achieved by electroporation (EPO). To evaluate mitochondrial biogenesis, such as NADH dehydrogenase (NADH), cytochrome c oxidase subunit Ⅳ (COXⅣ), citrate synthase (CS) were analyzed 2 and 4 weeks post PPARδ overexpression by EPO. Two and four weeks after PPARδ EPO, PPARδ expression in muscle was increased 2.1 and 2.8 fold respectively when compared to empty vector (EV) treated muscle. Two weeks after PPARδ EPO in muscle, PGC-1α, COXⅣ, and CS were not increased, but NADH and SUO were increased 1.5 and 2.4 fold respectively when compared to EV treated muscle. Four weeks after PPARδ EPO in muscle, PGC-1α, COXⅣ, CS, NADH, and SUO were increased 1.6, 2.1, 1.8, 2, and 2.5 fold respectively when compared to EV treated muscle. Thus, this study demonstrated that PPARδ can increase PGC-1α by posttranscriptional mechanism causing mitochondrial biogenesis, and PPARδ can affect directly or indirectly mitochodrial biogenesis without PGC-1α.
참고문헌 (24)
- Akimoto, T., "Real-time imaging of peroxisome proliferator-activated receptor-gamma coactivator-1alpha promoter activity in skeletal muscles of living mice", American Journal of Physiology. Cell Physiology, 287(3), pp.C790~C796 (2004)
- Baar, K., "Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1", FASEB Journal, 16(14), pp.1879~1886 (2002)
- Braissant, O., "Differential expression of peroxisome proliferatoractivated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat", Endocrinology, 137(1), pp.354~366 (1996)
- Garcia-Roves, P., "Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle", Proceedings of the National Academy of Sciences, 104(25), pp.10709~10713 (2007)
- Goto, M., "cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats", Biochemical and Biophysical Research Communications, 274(2), pp.350~354 (2000)
- Hancock, C. R., "High-fat diets cause insulin resistance despite an increase in muscle mitochondria", Proceedings of the National Academy of Sciences of the United States of America, 105(22), pp.7815~7820 (2008)
- Higashida, K., "Normal adaptations to exercise despite protection against oxidative stress", American Journal of Physiology. Endocrinology and Metabolism, E779(E784) (2011)
- Holloszy, J. O., "Biochemical adaptations in muscle effects of exercise on mitochondrial effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle", The Journal of Biological Chemistry, 242(9), pp.2278~2282 (1967)
- Holloszy, J. O., "Regulation by exercise of skeletal muscle content of mitochondria and GLUT4", Journal of Physiology and Pharmacology, 59(Suppl. 7), pp.5~18 (2008)
- Kelly, D. P., "Transcriptional regulatory circuits controlling mitochondrial biogenesis and function", Genes & Development, 18(4), pp.357~368 (2004)
- Kim, S. H., "β-Adrenergic stimulation does not activate p38 MAP kinase or induce PGC-1 in skeletal muscle. American Journal of Physiology", Endocrinology and Metabolism, 304(8), pp.E844~E852 (2013)
- Lin, J., "Metabolic control through the PGC-1 family of transcription coactivators", Cell Metabolism, 1(6), pp.361~370 (2005)
- Lowry, O. H., "Protein measurement with the Folin phenol reagent", The Journal of Biological Chemistry, 193(1), pp.265~275 (1951)
- Luquet, S., "Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability", FASEB Journal, 17(15), pp.2299~2301 (2003)
- Puigserver, P., "A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis", Cell, 92(6), pp.829~839 (1998)
- Scarpulla, R. C., "Nuclear activators and coactivators in mammalian mitochondrial biogenesis", Biochimica Et Biophysica Acta, 1576(1-2), pp.1~14 (2002)
- Scarpulla, R. C., "Nuclear control of respiratory gene expression in mammalian cells", Journal of Cellular Biochemistry, 97(4), pp.673~683 (2006)
- Tanaka, T., "Activation of peroxisome proliferatoractivated receptor δ induces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome", Proceedings of the National Academy of Sciences, 100(26), pp.15924~15929 (2003)
- Terada, S., "Effects of acute bouts of running and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle", American Journal of Physiology. Endocrinology and Metabolism, 286(2), pp.E208~E216 (2004)
- Terada, S., "Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle", Biochemical and Biophysical Research Communications, 296(2), pp.350~354 (2002)
- Wang, Y. X., "Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity", Cell, 113(2), pp.159~170 (2003)
- Wang, Y. X., "Regulation of muscle fiber type and running endurance by PPARdelta", PLoS Biology, 2(10), pp.e294~ (2004)
- Wende, A. R., "PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism", Molecular and Cellular Biology, 25(24), pp.10684~10694 (2005)
- Terada, S., "Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle", Biochemical and Biophysical Research Communications, 296(2), pp.350~354 (2002)