수태 전과 수태 중 모체운동 훈련이 어미 쥐와 새끼 쥐의 골격근 세포 내 미토콘드리아 생합성 요소에 미치는 영향
Mitochondrial Biosynthesis Factors of Offspring before and during Maternal Training Exercise in Rat Skeletal Muscle
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
이 연구는 수태 전 혹은 수태 중 모체의 유산소 운동 훈련이 자식의 근 세포 내 미토콘드리아 생합성 요소에 미치는 영향을 평가하려는 목적으로 계획되었다. 10주령 Sprague-Dawley 암컷 쥐(Samtako, Korea)를 대조(CON), 수태 전 운동(EBP), 수태 중 운동(EDP) 그룹으로 구분하여 각각 7마리씩 총 21마리를 사용하였다. 운동그룹은 총 10주(EBP) 및 3주(EDP)간 주 5회, 일일 1시간, 동물용 트레드밀에서 60-75 %VO2max 강도로 운동훈련을 실시하였다. 수태 전·중 모체의 운동훈련 효과와 태어난 새끼 쥐의 미토콘드리아 생합성 요소를 시기별(출산 직후, 출산 8주후)로 평가하기 위해 미토콘드리아 생합성(COX-Ⅳ, mtTFA, PGC-1α)과 모세혈관형성(VEGF165, VEGFtotal, HIF-1α) 인자들의 발현을 western blot 기법으로 분석하였다. 실험결과 수태 전 운동수행 그룹(EBP)과 수태 중 운동수행 그룹(EDP)에서 모체의 mtTFA(15%, 19%), PGC-1α(28%, 33%), VEGF165(14%, 19%) 단백질 발현이 대조그룹(CON)에 비해 높게 나타났다. Off-EDP 그룹의 골격근에서 출산 직후 COX-Ⅳ(35%), mtTFA(24%), PGC-1α(25%), VEGF165(17%), VEGFtotal(25%) 단백질 발현이 Off-CON 그룹에 비해 높게 나타났으며 그 영향은 8주 후까지 지속되었다. 이상의 결과를 요약하면, 수태 중인 모체의 규칙적인 유산소 훈련이 모체 뿐 만 아니라 새끼 쥐의 미토콘드리아 산화 능력과 혈관 생성을 향상시키며, 새끼 쥐의 유산소 대사능력은 모체가 수태 전에 운동 한 경우보다 수태 중에 운동하는 것이 출산 후 새끼의 대사능력에 보다 더 긍정적인 영향을 미친다.
Abstract
The present study was to investigate whether mitochondrial biosynthetic markers of offspring is affected by maternal exercise training during pregnancy. Twenty-one SD rats (10 wks) were randomly assigned into CON (control, n=7), EBP (exercise before pregnancy, n=7) and EDP (exercise during pregnancy, n=7) group. Exercise groups ran on the rodent treadmill at 60-75 %VO2max for 10 weeks (1 h/d, 5 d/wk). Muscle samples were obtained from offsprings at immediately after and 8 weeks after birth, and mother rats were also sacrificed 4 weeks after delivering the offspring. Mitochondrial biosynthetic markers, COX-Ⅳ, mtTFA, PGC-1α proteins and angiogenesis factors, VEGF165, VEGFtotal, HIF-1α proteins were measured by western blotting. The expression of maternal PGC-1α, mtTFA, and COX-Ⅳ proteins in both EBP and EDP groups were significantly upregulated than CON group after aerobic exercise training. The expression of maternal VEGF165, VEGFtotal were significantly upregulated than CON group after aerobic exercise training, whereas no difference in HIF-1α protein level were found among the groups. The expression of COX-Ⅳ, mtTFA, PGC-1α protein levels of offsprings in EDP group were similar to maternal values and significantly higher than EBP and CON groups immediately after birth and maintained up to 8 weeks after birth. The trend of angiogenesis factors, VEGF165, VEGFtotal, HIF-1α proteins of offsprings also similar to mitochondrial biosynthetic markers immediately after and 8 weeks after birth as well. In summary, prolonged and regular maternal aerobic exercise during pregnancy increases mitochondrial biosynthetic and angiogenetic factors in skeletal muscles in both maternal and offsprings. Furthermore, prolonged and regular maternal aerobic exercise during pregnancy maintains upregulated levels of mitochondrial biosynthetic and angiogenetic factors during growth and development of offsprings.
참고문헌 (33)
- Alam, T. I., "Human mitochondrial DNA is packaged with TFAM", Nucleic Acids Res, 31(6), pp.1640~1645 (2003)
- Anderson, S., "Sequence and organization of the human mitochondrial genome", Nature, 290(5806), pp.457~465 (1981)
- Bibb, M. J., "Sequence and gene organization of mouse mitochondrial DNA", Cell, 26(2 Pt 2), pp.167~180 (1981)
- Boney, C . M., "Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus", Pediatrics, 115(3), pp.e290~e296 (2005)
- Briston, T., "HIF-1α localization with mitochondria: a new role for an old favorite", Cell Cycle, 10(23), pp.4170~4171 (2011)
- Bustamante-Ara, N., "ACE and ACTN3 genes and muscle phenotypes in nonagenarians", Int. J. Sports Med, 31(4), pp.221~224 (2010)
- Carter, L. G., "Maternal exercise improves insulin sensitivity in mature rat offspring", Med. Sci. Sports Exerc, 45(5), pp.832~840 (2013)
- Catalano, P. M., "Perinatal risk factors for childhood obesity and metabolic dysregulation", Am. J. Clin. Nutr, 90(5), pp.1303~1313 (2009)
- Catalano, P. M., "Fetuses of obese mothers develop insulin resistance in utero", Diabetes Care, 32(6), pp.1076~1080 (2009)
- Dabelea, D., "Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity:a study of discordant sibships", Diabetes, 49(12), pp.2208~2211 (2000)
- Ekstrand, M. I., "Mitochondrial transcription factor A regulates mtDNA copy number in mammals", Hum. Mol. Genet, 13(9), pp.935~944 (2004)
- Falkenberg, M., "DNA replication a nd t ranscription in m ammalian mitochondria", Annu. Rev. Biochem, 76, pp.679~699 (2007)
- Ferrara, N., "Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene", Nature, 380(6573), pp.439~442 (1996)
- Geng, T., "PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle", Am. J. Physiol. Cell Physiol, 298(3), pp.c572~c579 (2010)
- Gluckman, P. D., "Epigenetic mechanisms that underpin metabolic and cardiovascular diseases", Nat. Rev. Endocrinol, 5(7), pp.401~408 (2009)
- Herrera, E., "Maternal lipid metabolism and placental lipid transfer", Horm. Res, 65(Suppl 3), pp.59~64 (2006)
- Jirtle, R. L., "Environmental epigenomics and disease susceptibility", Nat. Rev. Genet, 8(4), pp.253~262 (2007)
- Johnson, M. L., "Skeletal muscle aging and the mitochondrion", Trends Endocrinol. Metab, 24(5), pp.247~256 (2013)
- Larsson, N. G., "Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice", Nat. Genet, 18(3), pp.231~236 (1998)
- Leick, L., "PGC-1α is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle", Exp. Gerontol, 45(5), pp.336~342 (2010)
- May, L. E., "Regular maternal exercise dose and fetal heart outcome", Med. Sci. Sports Exerc, 44(7), pp.1252~1258 (2012)
- Melzer, K., "Physical activity and pregnancy: cardiovascular adaptations, recommendations and pregnancy outcomes", Sports Med, 40(6), pp.493~507 (2010)
- Newgard, C. B., "The family of glycogen phosphorylases: structure and function", Crit. Rev. Biochem. Mol. Biol, 24(1), pp.69~99 (1989)
- Pellegrini, M., "MTERF2 is a nucleoid component in mammalian mitochondria", Biochim. Biophys. Acta, 1787(5), pp.296~302 (2009)
- Peterson, C. M., "Skeletal muscle mitochondria and aging: a review", J. Aging research, pp.194821~ (2012)
- Rinaldi, B., "Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training", PLoS One, 8(7), pp.e69954~ (2013)
- Russell, A. P., "Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle", Diabetes, 52(12), pp.2874~2881 (2003)
- Semenza, G. L., "HIF-1 and human disease: one highly involved factor", Genes Dev, 14(16), pp.1983~1991 (2000)
- Sparks, J. W., "An estimate of the caloric requirements of the human fetus", Biol. Neonate, 38(3-4), pp.113~119 (1980)
- Sriwijitkamol, A., "LKB1-AMPK signaling in muscle from obese insulin-resistant zucker rats and effects of training", Am. J. Physiol. Endocrinol. Metab, 290(5), pp.E925~E932 (2006)
- Timmons, J. A., "Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans", J. Appl. Physiol, 108(6), pp.1487~1496 (2010)
- Wright, D. C., "Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression", J. Biol. Chem, 282(1), pp.194~199 (2007)
- Yan, Z., "E xercise t raining-induced regulation of mitochondrial quality", Exerc. Sport Sci. Rev, 40(3), pp.159~164 (2012)
