탈신경과 무용 후 흰쥐 골격근의 근위축에서 세포자멸사 관련인자의 변화
Changes of Apoptosis Related Factors in Atrophic Rat Skeletal Muscles after Denervation and Disuse
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective: To investigate the changes of apoptosis related factors after denervation and disuse in skeletal muscles and to find out the role of apoptosis in atrophic process. Method: 30 male Sprague-Dawley rats, 8 weeks of age were treated with three different atrophy models (10 rats in each group); hind-limbs suspension (HS) as a disuse model, complete denervation by sciatic nerve transsection (CD) and partial denervation by sciatic nerve crushing (PD). At 2 weeks and 4 weeks after each experiment, both gastrocnemius were dissected and their weights were measured. Western blotting for BAX and Bcl-2 and TUNEL assay were used to assess the changes of apoptosis related factors in muscle cell. Results: The muscle weight of PD and CD group decreased 38.6%, 65.6%, respectively, of intact side at 4 weeks after injuries. The loss of muscle weight in HS group was smaller than that of denervated muscles. CD group showed high expression of BAX (3.45±0.32→2.87±0.48) and Bcl-2 (3.63±0.40→3.33±0.50) at 2 and 4 weeks after denervation, but in PD group, BAX at 2 weeks significantly decreased at 4 weeks (3.40±0.55→2.13±0.25). In HS group, their expressions were slightly increased only immediate after 14 days suspension (BAX: 1.30±0.38 and Bcl-2: 1.29±0.28). CD group showed higher number of positive nuclei (27.6±8.8%) than PD group (10.4±5.3%) and HS group (4.4±1.6%) in TUNEL assay. Conclusion: Unlike temporary increase of apoptosis related factors in disuse, increase of these factors are remarkable and persisted after denervation. Muscle apoptosis may be the major cause of muscle atrophy during degeneration process.
Abstract
Objective: To investigate the changes of apoptosis related factors after denervation and disuse in skeletal muscles and to find out the role of apoptosis in atrophic process. Method: 30 male Sprague-Dawley rats, 8 weeks of age were treated with three different atrophy models (10 rats in each group); hind-limbs suspension (HS) as a disuse model, complete denervation by sciatic nerve transsection (CD) and partial denervation by sciatic nerve crushing (PD). At 2 weeks and 4 weeks after each experiment, both gastrocnemius were dissected and their weights were measured. Western blotting for BAX and Bcl-2 and TUNEL assay were used to assess the changes of apoptosis related factors in muscle cell. Results: The muscle weight of PD and CD group decreased 38.6%, 65.6%, respectively, of intact side at 4 weeks after injuries. The loss of muscle weight in HS group was smaller than that of denervated muscles. CD group showed high expression of BAX (3.45±0.32→2.87±0.48) and Bcl-2 (3.63±0.40→3.33±0.50) at 2 and 4 weeks after denervation, but in PD group, BAX at 2 weeks significantly decreased at 4 weeks (3.40±0.55→2.13±0.25). In HS group, their expressions were slightly increased only immediate after 14 days suspension (BAX: 1.30±0.38 and Bcl-2: 1.29±0.28). CD group showed higher number of positive nuclei (27.6±8.8%) than PD group (10.4±5.3%) and HS group (4.4±1.6%) in TUNEL assay. Conclusion: Unlike temporary increase of apoptosis related factors in disuse, increase of these factors are remarkable and persisted after denervation. Muscle apoptosis may be the major cause of muscle atrophy during degeneration process.
참고문헌 (21)
- Booth FW, "Time course of muscular atrophy during immobilization of hindlimbs in rats", J Appl Physiol, 43, pp.656~661 (1977)
- Borisov AB, "Cell death in denervated skeletal muscle is distinct from classical apoptosis", Anat Rec, 258, pp.305~318 (2000)
- Jejurikar SS, "Skeletal muscle denervation increases satellite cell susceptibility to apoptosis", Plast Reconstr Surg, 110, pp.160~168 (2002)
- Olive M, "Bcl-2 and bax immunohistochemistry in denervation-reinnervation and necrosis-regeneration of rat skeletal muscles", Muscle Nerve, 23, pp.1862~1867 (2000)
- Baldwin KM, "Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms", Am J Phys Med Rehabil, 81, pp.S40~S51 (2002)
- Caiozzo VJ, "Plasticity of skeletal muscle phenotype: mechanical consequences", Muscle Nerve, 26, pp.740~768 (2002)
- Tews DS, "Apoptosis and muscle fibre loss in neuromuscular disorders", Neuromuscul Disord, 12, pp.613~622 (2002)
- Green DR, "Mitochondria and apoptosis", Science, 281, pp.1309~1312 (1998)
- Siu PM, "Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle", J Physiol, 565, pp.309~323 (2005)
- Phaneuf S, "Apoptosis and exercise", Med Sci Sports Exerc, 33, pp.393~396 (2001)
- Lim HS, "The electromicroscopic study on the development of knee joint in rat", Korean J Anat, 33, pp.339~351 (2000)
- Carlson BM, "Muscle regeneration in young and old rats: effects of motor nerve transection with and without marcaine treatment", J Gerontol A Biol Sci Med Sci, 53, pp.B52~B57 (1998)
- Ide C, "Peripheral nerve regeneration", Neurosci Res, 25, pp.101~121 (1996)
- Morey-Holton ER, "Hindlimb unloading rodent model: technical aspects", J Appl Physiol, 92, pp.1367~1377 (2002)
- Chen SP, "Decline in titin content in rat skeletal muscle after denervation", Muscle Nerve, 32, pp.798~807 (2005)
- Lim JY, "The effect of electromyostimulation on apoptosis in denervation and reinnervation of rat skeletal muscles", 박사, pp.2006
- Tews DS, "Muscle-fiber apoptosis in neuromuscular diseases", Muscle Nerve, 32, pp.443~458 (2005)
- Siu PM, "Id2 and p53 participate in apoptosis during unloading-induced muscle atrophy", Am J Physiol Cell Physiol, 288, pp.C1058~C1073 (2005)
- McKinnell IW, "Molecular mechanisms of muscle atrophy", Cell, 119, pp.907~910 (2004)
- Thissen JP, "Towards an understanding of molecular mechanisms of muscle atrophy", Curr Opin Clin Nutr Metab Care, 8, pp.245~247 (2005)
- Dirks AJ, "The role of apoptosis in age- related skeletal muscle atrophy", Sports Med, 35, pp.473~483 (2005)