跳到主要內容

臺灣博碩士論文加值系統

(44.211.117.197) 您好!臺灣時間:2024/05/21 03:34
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:陳冠霖
研究生(外文):Guan-Lin Chen
論文名稱:探討硫辛酸在骨骼肌細胞對於脂多醣體氧化壓力之保護作用
論文名稱(外文):Study on the Protective Effects of Lipoic Acid in Skeletal Muscle under Lipopolysaccharide Oxidative Stress
指導教授:吳佩芳吳佩芳引用關係
指導教授(外文):Pei-Fung Wu
學位類別:碩士
校院名稱:國立高雄大學
系所名稱:運動健康與休閒學系碩士班
學門:民生學門
學類:運動休閒及休閒管理學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:51
中文關鍵詞:脂多醣體硫辛酸氧化傷害
外文關鍵詞:LipopolysaccharideLipoic acidOxidative stress
相關次數:
  • 被引用被引用:1
  • 點閱點閱:187
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
  本研究將小鼠肌纖維母細胞 C2C12細胞株以含10%馬血清的分化培養液培養3至5天分化為myotube,探討硫辛酸對骨骼肌細胞接受脂多醣體氧化傷害後的抗凋亡路徑。我們藉由西方墨點法分析蛋白質,結果發現,硫辛酸在5 μM、50 μM及0.5 mM作用濃度會增加磷酸化 Akt (p-Akt)與 Bcl-xL蛋白質表現量,但投予5 mM及10 mM硫辛酸會減少 p-Akt與 Bcl-xL蛋白質表現量。此外,硫辛酸在第4、5小時作用時間會減少 p-Akt與 Bcl-xL蛋白質表現量。以上結果顯示,硫辛酸在高劑量與長時間作用下對 myotube可能具有毒性;但低劑量硫辛酸對細胞可能具有保護作用。另一方面,細胞投予脂多醣體則會降低 p-Akt與 Bcl-xL蛋白質表現量,並且在20 μg/mL脂多醣體作用下蛋白質表現量達到最低。此外,Toll-like receptor-4 (TLR4)蛋白質則隨細胞投予脂多醣體而增加。以上結果顯示,脂多醣體透過 TLR4的活化誘發氧化傷害並且會降低 p-Akt與 Bcl-xL蛋白質表現而對 myotube造成傷害。接著將 p-Akt抑制劑 LY294002加入 myotube中抑制 p-Akt後發現 Bcl-xL蛋白質也隨之被抑制,顯示硫辛酸可能經由活化 p-Akt影響 Bcl-xL的表現。另一方面,實驗結果顯示將脂多醣體投予含抑制劑 LY294002的 myotube之後,硫辛酸並無法影響 p-Akt與 Bcl-xL的表現量。而根據實驗結果顯示硫辛酸可藉由提升 p-Akt與 Bcl-xL蛋白質表現量保護 myotube免於氧化傷害。綜合本實驗發現,在 myotube中硫辛酸對脂多醣體引發的傷害可能經由 PI3K/Akt pathway達到保護的效果。
In this study, we evaluate the anti-apoptosis pathway of lipoic acid under lipopolysaccha- ride oxidative stress in mouse skeletal cell line (C2C12). The mature myotubes were different- iated from C2C12 cells growth on 10% horse serum differentiation medium 3-5 days. The result of western blotting shows the level of phosphorylate Akt and Bcl-xL protein was incre- ased in the 5μM, 50μM and 0.5mM of lipoic acid treatment and the protein level was decreas- ed especially in 5mM and 10mM lipoic acid treatment. Therefore, the level of phosphorylate Akt and Bcl-xL protein was decreased at the 4, 5 hours treatment. It was shown the high dose and long-term treatment of lipoic acid may induce toxicity in myotubes, but low dose of lipoic acid may protect cells from damage. On the other hand, the phosphorylate Akt and Bcl-xL proteins were decreased by after treatment of lipopolysaccharide, especially in the dosage of 20μg/ml. Moreover, the level of TLR4 protein was expressed after lipopolysaccharide treatm- ent. These results show that oxidative stress of lipopolysaccharide in myotubes were induced by TLR4 protein and may induce oxidative stress by lower the express of phosphorylate Akt and Bcl-xL proteins. Furthermore, the level of Bcl-xL was inhibited after treatment with LY294002. It shows the express of Bcl-xL was regulated by p-Akt. Our results also show after treatment of lipopolysaccharide, lipoic acid can not affect the express of p-Akt and Bcl-xL in myotubes containing LY294002. According to our results, it shows that lipoic acid could against myotubes from oxidative stress by enhancing the express of p-Akt and Bcl-xL protein. It is indicated the lipoic acid against myotubes from lipopolysaccharide stress by PI3K/Akt pathway.
目錄.......................................................................Ⅰ
圖目錄.....................................................................Ⅱ
中文摘要....................................................................1
英文摘要....................................................................3
第一章 前言................................................................5
第二章 研究方法與材料.....................................................12
第三章 結果...............................................................17
第四章 討論...............................................................23
第五章 結論...............................................................27
第六章 參考文獻...........................................................44
Bast, A., and Haenen, G. R. M. M. (2002). The toxicity of antioxidants and their metabolites. Environmental Toxicology and Pharmacology, 11, 251-258.
Beutler, B. (2000). Tlr4: Central component of the sole mammalian LPS sensor. Current Opinion in Immunology, 12, 20-26.
Bonetto, A., Penna, F., Muscaritoli M., Minero, V. G., Fanelli, F. R., Baccino, F. M., and Costelli, P. (2009). Are antioxidants useful for treating skeletal muscle atrophy? Free Radical Biology and Medicine, 47, 906-916.
Bradshaw, R. A., and Dennis, E. A. (2004). Handbook of cell signaling, Amsterdam: Academic Press.
Ceriello, A. (2000). Oxidative stress and glycemic regulation. Metabolism, 49, 27-29.
Coleman, M. D., Eason, R. C., and Bailey, C. J. (2001). The therapeutic use of lipoic acid in diabetes: A current perspective. Environmental Toxicology and Pharmacology, 10, 167-172.
Cross, T. G., Scheel, T. D., Henriquez, N. V., Deacon, E., Salmon, M., and Lord, J. M. (2000). Serine/Threonine protein kinases and apoptosis. Experimental Cell Research, 256, 34-41.
Downward, J. (2004). PI 3-kinase, Akt and cell survival. Seminars in Cell and Developmental Biology, 15, 177-182.
Gisone, P., Robello, E., Sanjurjo, J., Dubner, D., Perez, M. R., Michelin, S., and Puntarulo, S. (2006). Reactive species and apoptosis of neural precursor cells after gamma-irradiation. Neurotoxicology, 27, 253-259.
Holmquist, L., Stuchbury, G., Berbaum, K., Muscat, S., Young, S., Hager, K., Engel, J., and Münch, G. (2007). Lipoic acid as a novel treatment for Alzheimer's disease and related dementias. Pharmacology and Therapeutics, 113, 154-164.
Jiang, B. H., and Liu, L. Z. (2009). PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv. Cancer Res., 102, 19-65.
Kawanishi, N., Tanaka, Y., Kato, Y., Shiva, D., and Yano, H. (2008). Lipopolysaccharide-in- duced monocyte chemotactic protein-1 is enhanced by suppression of nitric oxide produ- ction, which depends on poor CD14 expression on the surface of skeletal muscle. Cell Biochemistry and Function, 26, 486-492.
Kim, H.Y., Oi, Y., Kim, M., and Yokozawa, T. (2008). Protective effect of lipoic acid against methylglyoxal-induced oxidative stress in LLC-PK1 cells. J. Nutr. Sci. Vitaminal, 54, 99-104.
Khanna, S., Roy, S., Packer, L., and Sen, C. K. (1999). Cytokine-induced glucose uptake in skeletal muscle: Redox regulation and the role of alpha-lipoic acid. Am. J. Physiol., 276, R1327-1333.
Kowluru, R. A., and Chan, P. S. (2007). Oxidative stress and diabetic retinopathy. Experimental Diabetes Research, 2007, 43603-43615.
Leonard, S. S., Harris, G. K., and Shi, X. (2004). Metal-induced oxidative stress and signal transduction. Free Radical Biology and Medicine, 37(12), 1921-1942.
Lu, Y. C., Yeh, W. C., and Ohashi, P. S. (2008). LPS/TLR4 signal transduction pathway. Cytokine, 42, 145-151.
Packer, L., Witt, E. H., and Tritschler, H. J. (1995). Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine, 19(2), 227-250.
Rachek, L. I., Musiyenko, S. I., LeDoux, S. P., and Wilson, G. L. (2007). Palmitate induced mitochondrial deoxyribonucleic acid damage and apoptosis in L6 rat skeletal muscle cells. (2007). Endocrinology, 148(1), 293-299.
Sadiq, F., Hazlerigg, D. G., and Lomax, M. A. (2007). Amino acids and insulin act additively to regulate components of the ubiquitin-proteasome pathway in C2C12 myotubes. BMC Molecular Biology, 8(23), 1-12.
Shi, D. Y., Liu, H. L., Stern, J. S., Yu, P. Z., and Liu, S. L. (2008). Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway. FEBS Letters, 582, 1667-1671.
Singh, L. P., Gennerette, D., Simmons, S., and Crook, E. D. (2001). Glucose-induced insulin resistance of phosphatidylinositol 3-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. Journal of Diabetes and Its Complications, 15, 88-96.
Singh, U., and Jialal, I. (2008). Alpha-lipoic acid supplementation and diabetes. Nutr. Rev., 66(11), 646-657.
Stiles, B. L. (2009). PI-3-K and AKT: Onto the mitochondria. Advanced Drug Delivery Reviews, 61, 1276-1282.
Suh, J. H., Wang, H., Liu, R. M., Liu, J., and Hagen, T. M. (2004). (R)-alpha-lipoic acid
reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch. Biochem. Biophys., 423, 126−135.
Sumbayev, V. V. (2007). PI3 kinase and direct S-nitrosation are involved in down-regulation of apoptosis signal-regulating kinase 1 during LPS-induced Toll-like receptor 4 signalling. Immunology Letters, 115, 126-130.
Thompson, J. E. and Thompson, C. B. (2004). Putting the rap on Akt. Journal of Clinical Oncology, 22, 4217-4226.
Vasdev, S., Gill, V. D., and Singal, P. K. (2006). Modulation of oxidative stress-induced changes in hypertension and atherosclerosis by antioxidants. Experimental Cardiology, 11(3), 206-216.
Vinatier, D., Dufour, Ph., and Subtil, D. (1996). Apoptosis: A programmed cell death involved in ovarian and uterine physiology. European Journal of Obstetrics and Gynecology and Reproductive Biology, 67, 85-102.
Weinstein, R. B., Tritschler, H. J., and Henriksen, E. J. (2001). Antioxidant alpha-lipoic acid and protein turnover in insulin-resistant rat muscle. Free Radical Biology and Medicine, 30(4), 383-388.
Zhang, W. J., Wei, H., Hagen, T., and Frei, B. (2007). α-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. P.N.A.S., 104(10), 4077-4082.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top