MEHP及癌症惡病質症對骨骼肌萎縮的加乘性影響

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廖怡萱(Yi-Shiuan Liao) 查詢紙本館藏

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MEHP及癌症惡病質症對骨骼肌萎縮的加乘性影響
(The synergistic effect of MEHP and cancer cachexia on skeletal muscle atrophy)

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至系統瀏覽論文 (2026-7-31以後開放)

摘要(中)

塑化劑廣泛存在於人們的日常生活中，保鮮膜、化妝品、藥品、醫療器材與保健食品膠囊等，都含有塑化劑。其中Di(2-ethylhexyl)phthalate (DEHP)是最常見的塑化劑，經各種途徑吸收了DEHP後會迅速代謝成MEHP進入循環系統中，進而影響內分泌、生殖、生長與代謝等生理功能。先前研究發現，加入MEHP會抑制肌肉細胞生長分化(myogenesis)。癌症惡病質症(cancer cachexia)是一種不可逆的併發症，癌細胞會釋放促發炎因子(TNFα、IL-6、INFγ)等可溶性因子影響遠端器官，活化泛素蛋白酶系統(ubiquitin-proteasome system)及自噬途徑，導致肌肉嚴重萎縮。癌症惡病質症患者大部分是癌症晚期的患者，在長期住院治療下大幅增加了從點滴管醫療器材吸收DEHP的風險。因此本計畫假設暴露在高量的DEHP中會加劇癌症惡病質症的骨骼肌流失，以探討MEHP及癌症惡病質症對骨骼肌萎縮的加乘性影響。我利用C26結腸癌細胞釋放出的可溶性物質(C26M)來模擬cancer cachexia的環境。實驗發現，C26M藉由調控C2C12肌肉細胞中MuRF1與Atrogin 1的啟動子與mRNA穩定性來使MuRF1表現量下降，Atrogin 1表現量上升。MuRF1與Atrogin 1相反的趨勢指出C26M透過不同路徑影響其表現。此外，MEHP與C26M共同抑制C2C12肌管的形成與細胞中肌肉分化因子(MyoG、Mef2c)的mRNA表現量，且C2C12細胞中ROS含量也受到MEHP與C26M共同上調。in vivo的實驗發現，DEHP使C26小鼠腓腸肌(GC)更加萎縮，且只有在DEHP/C26組別的小鼠中發現比目魚肌(Soleus)有萎縮的情形。在分子層面，C26小鼠肥腸白肌中的E3-泛素連接酶(MuRF1、Atrogin 1)表現量皆上升，而DEHP對E3-泛素連接酶表現量並無加乘影響。C26小鼠骨骼肌中MuRF1 mRNA表現量上升的趨勢與in vitro實驗中觀察到的現象相反，推測有其他系統(如神經系統、免疫系統等)參與其中。與正常小鼠相比，C26小鼠脾臟明顯腫大，暗示其體內可能發生嚴重發炎反應。Raw264.7巨噬細胞培養液(RM)及受C26M刺激之巨噬細胞培養液(RC)會與C26M共同促進C2C12成熟肌管的萎縮，未來還需探討免疫細胞是否調控E3-泛素連接酶mRNA表現量。綜合以上所述，DEHP/MEHP會加劇癌症惡病質症的肌肉流失，造成癌症惡病質症的惡化。

摘要(英)

Plasticizers are widely present in people′s daily life, found in items such as cling film, cosmetics, pharmaceuticals, medical equipment, and health food capsules. Among them, Di (2-ethylhexyl) phthalate (DEHP) is the most common plasticizer, which is easily leached out from PVC products. Once it enters the human body, it is rapidly metabolized to mono-2-ethylhexyl phthalate (MEHP) and then enters the circulatory system, affecting physiological functions such as endocrine system, reproductive, growth, and metabolism. Previous studies have shown that MEHP represses skeletal muscle (SKM) differentiation. Cancer cachexia is an irreversible wasting syndrome of muscle and fat induced by signals from cancer and immune cells. Given the high levels of DEHP exposure in long-term hospitalized cancer patients due to continuous contact with PVC tubing and medical equipment, we hypothesize that DEHP exposure exacerbates muscle wasting in cancer patients. Here I found that cancer cachexia factors contained in the C26 colon cancer cells conditioned medium (C26M) differentially modulate the promoter activity and mRNA stability of E3 ligases MuRF1 and Atrogin1, resulting in decreased MuRF1 expression and increased Atrogin 1 expression in C2C12 myoblasts and myotubes. Moreover, MEHP and C26M synergistically inhibited the myogenic capacity of C2C12 and the mRNA expression of muscle differentiation factors (MyoG, Mef2c), along with elevated ROS levels in these cells. In vivo experiments showed that DEHP caused further atrophy of the gastrocnemius (GC) muscle in mice with C26 tumor (C26 mice). Of note, soleus atrophy was only observed in mice treated with DEHP/C26. In contrast to the observations in C2C12 myoblasts, the mRNA expression of MuRF1 and Atrogin 1 was both increased in the GC muscle of C26 mice, suggesting the involvement of other cell types, such as neuron and immune cells, in vivo. Additionally, C26 mice exhibited significant splenomegaly compared to normal mice, indicating severe inflammatory responses. Culturing with Raw264.7 macrophage conditioned medium (RM) and C26M-stimulated macrophage conditioned medium (RC) intensified myotube atrophy in C2C12, suggesting a potential role of immune cells in regulating E3 ubiquitin ligase mRNA expression. In conclusion, DEHP/MEHP exacerbates muscle wasting in cancer cachexia, contributing to its deterioration.

關鍵字(中)

★ 塑化劑
★ 癌症惡病質症
★ 骨骼肌
★ 萎縮

關鍵字(英)

★ MEHP
★ DEHP
★ cancer cachexia
★ skeletal muscle
★ atrophy

論文目次

摘要 v
Abstract vi
聲明(Declaration) viii
誌謝(Acknowledgment) ix
目錄 x
縮寫與全名對照表 (Abbreviations) xiv
第一章、緒論 1
1-1. 肌肉生成過程(Myogenesis) 1
1-2. 塑化劑(DEHP/MEHP) 2
1-3. 癌症惡病質症(Cancer cachexia) 4
1-4. E3-泛素連接酶與肌肉萎縮 5
1-5. 研究動機及研究問題 7
第二章、實驗材料及方法 9
2-1. 細胞株(Cell lines) 9
2-1.1. 老鼠肌纖維母細胞: Mouse myoblast cells (C2C12) 9
2-1.2. 小鼠纖維母細胞: Fibroblast cells (C3H/10T1/2) 9
2-1.3. 穩定細胞株: C2C12-pStable、C2C12-MuRF1 promoter、C2C12-Atrogin 1 promoter 9
2-1.4. 穩定細胞株: C2C12-tTA-MyoD、C2C12-tTA-MyoG 9
2-1.5. 穩定細胞株: 10T1/2-tTA-MyoD 9
2-1.6. 小鼠結腸癌細胞: Mouse colon carcinoma (C26) 10
2-2. 質體列表(Plasmid list) 10
2-3. 細胞轉染(Cell transfection) 11
2-4. 冷光素酶報導檢測(Luciferase reporter assay) 11
2-5. RNA萃取(RNA extraction) 11
2-6. 反轉錄聚合酶連鎖反應(Reverse-transcription PCR, RT-PCR) 12
2-7. 即時定量聚合酶連鎖反應(qRT-PCR) 13
2-8. 細胞免疫螢光染色(Immunofluorescence) 13
2-9. 活性氧物質(Reactive oxygen species, ROS)含量檢測 14
2-9.1. DCFDA反應 14
2-9.2. 細胞懸浮及檢測 14
2-9.3. 蛋白質檢測及標準化 14
2-10. 抽取gDNA (gDNA extraction) 14
2-11. 粒線體含量測定(Mitochondria content determination) 15
2-12. 西方墨點法(Western blot) 15
2-12.1. Total protein extraction 15
2-12.4. Blocking及抗體辨識 16
2-12.5. 蛋白質上的抗體脫附(Stripping) 16
2-13. 小鼠管餵(mouse oral gavage)及皮下注射 17
2-13.1. 實驗動物 17
2-13.2. 試驗物質 17
2-13.3. 皮下注射 17
2-13.4. 管餵 17
2-14. 小鼠組織切取(mouse tissue dissection) 18
2-14.1. 麻醉小鼠 18
2-14.2. 心臟採血 18
2-14.3. 灌流 18
2-14.4. 取組織 18
第三章、結果 20
3-1. MuRF1與Atrogin 1為肌肉專一性基因，且在肌肉發育過程中大量表現 20
3-2. DEHP及cachexia signal對BALB/c小鼠的影響 20
3-1.1 第一批小鼠實驗 20
3-1.2 第二批小鼠實驗 21
3-3. MEHP及C26M共同誘導成熟肌管的萎縮 23
3-4. MEHP及C26M共同抑制C2C12的分化能力 24
3-5. MEHP與C26M對MuRF1及Atrogin 1 promoters活性的影響 24
3-6. 探討癌症惡病質訊號對MuRF1、Atrogin 1之mRNA穩定度的影響 25
3-7. MEHP與C26M提升C2C12中ROS含量，但不影響mtDNA含量 26
3-8. C26M與Raw264.7分泌之因子共同誘導肌管萎縮 26
3-9. MyoG調控MuRF1與Atrogin 1的表現 27
3-10. MyoD調控MuRF1與Atrogin 1的表現 28
第四章、討論 30
4-1. DEHP/MEHP與癌症惡病質症對肌肉分化的影響 30
4-2. C26M對MuRF1與Atrogin 1的調控 30
4-3. DEHP對快縮肌與慢縮肌的影響 31
4-4. MuRF1與Atrogin 1在C26小鼠心臟中的表現 31
4-5. 探討C26小鼠的免疫細胞是否影響骨骼肌分化 32
4-6. 利用C26-tTA-luciferase穩定細胞株觀察腫瘤細胞的形成與轉移 33
4-7. 結論與未來方向 33
第五章、圖表 34
Fig. 5-1 MuRF1與Atrogin 1為肌肉專一性基因，且在肌肉發育過程中大量表現 35
Fig. 5-2 第一批小鼠實驗 37
Fig. 5-3 第二批小鼠實驗 39
Fig. 5-4 MEHP及C26M對C2C12成熟肌管的影響 41
Fig. 5-5 MEHP及C26M對C2C12分化時期的影響 43
Fig. 5-6 MEHP與C26M對MuRF1及Atrogin 1 promoter活性的影響 44
Fig. 5-7 C26M對肌肉分化時MuRF1及Atrogin 1 mRNA穩定度的影響 45
Fig. 5-8 MEHP與C26M提升C2C12中ROS含量，但不影響mtDNA含量 46
Fig. 5-9 C26M與Raw264.7分泌之因子共同誘導肌管萎縮 47
Fig. 5-10 MyoG調控MuRF1與Atrogin 1的表現 49
Fig. 5-11 MyoD調控MuRF1與Atrogin 1的表現 51
第十章、參考文獻 52
第十一章、附錄 60
附錄一、補充圖表 60
附錄二、Primer list 65
附錄三、溶劑及溶液配方 67
附錄四、藥品試劑及抗體 69
附錄五、pStable-mMuRF1 promoter Sequence alignment 70
附錄六、pStable-mAtrogin 1 promoter Sequence alignment 72

參考文獻

1 Chen, Y. H. et al. MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells. Biosci Rep 40, doi:10.1042/BSR20194404 (2020).
2 Chen, S. L., Wu, C. C., Li, N. & Weng, T. H. Post-transcriptional regulation of myogenic transcription factors during muscle development and pathogenesis. J Muscle Res Cell Motil 45, 21-39, doi:10.1007/s10974-023-09663-3 (2024).
3 Koch, H. M., Preuss, R. & Angerer, J. Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an update and latest results. Int J Androl 29, 155-165; discussion 181-155, doi:10.1111/j.1365-2605.2005.00607.x (2006).
4 Asfour, H. A., Allouh, M. Z. & Said, R. S. Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery. Exp Biol Med (Maywood) 243, 118-128, doi:10.1177/1535370217749494 (2018).
5 Buckingham, M. & Rigby, P. W. Gene regulatory networks and transcriptional mechanisms that control myogenesis. Dev Cell 28, 225-238, doi:10.1016/j.devcel.2013.12.020 (2014).
6 Yokoyama, S. & Asahara, H. The myogenic transcriptional network. Cell Mol Life Sci 68, 1843-1849, doi:10.1007/s00018-011-0629-2 (2011).
7 Lassar, A. B. et al. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell 66, 305-315, doi:10.1016/0092-8674(91)90620-e (1991).
8 Zanou, N. & Gailly, P. Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways. Cell Mol Life Sci 70, 4117-4130, doi:10.1007/s00018-013-1330-4 (2013).
9 Jagarlapudi, S. S., Cross, H. S., Das, T. & Goddard, W. A., 3rd. Thermomechanical Properties of Nontoxic Plasticizers for Polyvinyl Chloride Predicted from Molecular Dynamics Simulations. ACS Appl Mater Interfaces 15, 24858-24867, doi:10.1021/acsami.3c02354 (2023).
10 Zota, A. R., Calafat, A. M. & Woodruff, T. J. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ Health Perspect 122, 235-241, doi:10.1289/ehp.1306681 (2014).
11 Roslev, P., Madsen, P. L., Thyme, J. B. & Henriksen, K. Degradation of phthalate and Di-(2-Ethylhexyl)phthalate by indigenous and inoculated microorganisms in sludge-amended soil. Appl Environ Microbiol 64, 4711-4719, doi:10.1128/AEM.64.12.4711-4719.1998 (1998).
12 Koch, H. M., Bolt, H. M. & Angerer, J. Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP. Arch Toxicol 78, 123-130, doi:10.1007/s00204-003-0522-3 (2004).
13 Serrano, S. E., Braun, J., Trasande, L., Dills, R. & Sathyanarayana, S. Phthalates and diet: a review of the food monitoring and epidemiology data. Environ Health 13, 43, doi:10.1186/1476-069X-13-43 (2014).
14 Inoue, K. et al. Evaluation and analysis of exposure levels of di(2-ethylhexyl) phthalate from blood bags. Clin Chim Acta 358, 159-166, doi:10.1016/j.cccn.2005.02.019 (2005).
15 Dhanapal, R., Saraswathi, T. & Govind, R. N. Cancer cachexia. J Oral Maxillofac Pathol 15, 257-260, doi:10.4103/0973-029X.86670 (2011).
16 Fearon, K. et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12, 489-495, doi:10.1016/S1470-2045(10)70218-7 (2011).
17 Ozola Zalite, I. et al. Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review. Pancreatology 15, 19-24, doi:10.1016/j.pan.2014.11.006 (2015).
18 Fearon, K. C., Glass, D. J. & Guttridge, D. C. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab 16, 153-166, doi:10.1016/j.cmet.2012.06.011 (2012).
19 Martignoni, M. E. et al. Liver macrophages contribute to pancreatic cancer-related cachexia. Oncol Rep 21, 363-369 (2009).
20 Barber, M. D., Fearon, K. C. & Ross, J. A. Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer. Clin Sci (Lond) 96, 83-87 (1999).
21 Baracos, V. E., Martin, L., Korc, M., Guttridge, D. C. & Fearon, K. C. H. Cancer-associated cachexia. Nat Rev Dis Primers 4, 17105, doi:10.1038/nrdp.2017.105 (2018).
22 Argiles, J. M., Lopez-Soriano, F. J. & Busquets, S. Mediators of cachexia in cancer patients. Nutrition 66, 11-15, doi:10.1016/j.nut.2019.03.012 (2019).
23 Guttridge, D. C., Mayo, M. W., Madrid, L. V., Wang, C. Y. & Baldwin, A. S., Jr. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 289, 2363-2366, doi:10.1126/science.289.5488.2363 (2000).
24 Ramamoorthy, S., Donohue, M. & Buck, M. Decreased Jun-D and myogenin expression in muscle wasting of human cachexia. Am J Physiol Endocrinol Metab 297, E392-401, doi:10.1152/ajpendo.90529.2008 (2009).
25 Tran, T., Andersen, R., Sherman, S. P. & Pyle, A. D. Insights into skeletal muscle development and applications in regenerative medicine. Int Rev Cell Mol Biol 300, 51-83, doi:10.1016/B978-0-12-405210-9.00002-3 (2013).
26 Cao, P. R., Kim, H. J. & Lecker, S. H. Ubiquitin-protein ligases in muscle wasting. Int J Biochem Cell Biol 37, 2088-2097, doi:10.1016/j.biocel.2004.11.010 (2005).
27 Ventadour, S. & Attaix, D. Mechanisms of skeletal muscle atrophy. Curr Opin Rheumatol 18, 631-635, doi:10.1097/01.bor.0000245731.25383.de (2006).
28 Penna, F., Ballaro, R. & Costelli, P. The Redox Balance: A Target for Interventions Against Muscle Wasting in Cancer Cachexia? Antioxid Redox Signal 33, 542-558, doi:10.1089/ars.2020.8041 (2020).
29 Khalil, R. Ubiquitin-Proteasome Pathway and Muscle Atrophy. Adv Exp Med Biol 1088, 235-248, doi:10.1007/978-981-13-1435-3_10 (2018).
30 Bodine, S. C. & Baehr, L. M. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab 307, E469-484, doi:10.1152/ajpendo.00204.2014 (2014).
31 Hughes, D. C. et al. Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism. Am J Physiol Cell Physiol 320, C45-C56, doi:10.1152/ajpcell.00432.2020 (2021).
32 Bodine, S. C. et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294, 1704-1708, doi:10.1126/science.1065874 (2001).
33 Clavel, S. et al. Regulation of the intracellular localization of Foxo3a by stress-activated protein kinase signaling pathways in skeletal muscle cells. Mol Cell Biol 30, 470-480, doi:10.1128/MCB.00666-09 (2010).
34 Sandri, M. et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117, 399-412, doi:10.1016/s0092-8674(04)00400-3 (2004).
35 Latres, E. et al. Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem 280, 2737-2744, doi:10.1074/jbc.M407517200 (2005).
36 Li, Y. P. et al. TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J 19, 362-370, doi:10.1096/fj.04-2364com (2005).
37 Karayiannakis, A. J. et al. Serum levels of tumor necrosis factor-alpha and nutritional status in pancreatic cancer patients. Anticancer Res 21, 1355-1358 (2001).
38 Llovera, M., Garcia-Martinez, C., Agell, N., Lopez-Soriano, F. J. & Argiles, J. M. TNF can directly induce the expression of ubiquitin-dependent proteolytic system in rat soleus muscles. Biochem Biophys Res Commun 230, 238-241, doi:10.1006/bbrc.1996.5827 (1997).
39 Centner, T. et al. Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J Mol Biol 306, 717-726, doi:10.1006/jmbi.2001.4448 (2001).
40 Laughter, A. R. et al. Role of the peroxisome proliferator-activated receptor alpha (PPARalpha) in responses to trichloroethylene and metabolites, trichloroacetate and dichloroacetate in mouse liver. Toxicology 203, 83-98, doi:10.1016/j.tox.2004.06.014 (2004).
41 Martinelli, M. I., Mocchiutti, N. O. & Bernal, C. A. Dietary di(2-ethylhexyl)phthalate-impaired glucose metabolism in experimental animals. Hum Exp Toxicol 25, 531-538, doi:10.1191/0960327106het651oa (2006).
42 Srinivasan, C., Khan, A. I., Balaji, V., Selvaraj, J. & Balasubramanian, K. Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat. Toxicol Appl Pharmacol 257, 155-164, doi:10.1016/j.taap.2011.08.022 (2011).
43 Kavlock, R. et al. NTP-CERHR Expert Panel Update on the Reproductive and Developmental Toxicity of di(2-ethylhexyl) phthalate. Reprod Toxicol 22, 291-399, doi:10.1016/j.reprotox.2006.04.007 (2006).
44 Huber, W. W., Grasl-Kraupp, B. & Schulte-Hermann, R. Hepatocarcinogenic potential of di(2-ethylhexyl)phthalate in rodents and its implications on human risk. Crit Rev Toxicol 26, 365-481, doi:10.3109/10408449609048302 (1996).
45 Doull, J. et al. A cancer risk assessment of di(2-ethylhexyl)phthalate: application of the new U.S. EPA Risk Assessment Guidelines. Regul Toxicol Pharmacol 29, 327-357, doi:10.1006/rtph.1999.1296 (1999).
46 Bonetto, A., Rupert, J. E., Barreto, R. & Zimmers, T. A. The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia. J Vis Exp, doi:10.3791/54893 (2016).
47 Liu, X. et al. Di-(2-ethyl hexyl) phthalate induced oxidative stress promotes microplastics mediated apoptosis and necroptosis in mice skeletal muscle by inhibiting PI3K/AKT/mTOR pathway. Toxicology 474, 153226, doi:10.1016/j.tox.2022.153226 (2022).
48 Reid, M. B. & Li, Y. P. Tumor necrosis factor-alpha and muscle wasting: a cellular perspective. Respir Res 2, 269-272, doi:10.1186/rr67 (2001).
49 Haddad, F., Zaldivar, F., Cooper, D. M. & Adams, G. R. IL-6-induced skeletal muscle atrophy. J Appl Physiol (1985) 98, 911-917, doi:10.1152/japplphysiol.01026.2004 (2005).
50 Zamir, O., Hasselgren, P. O., Higashiguchi, T., Frederick, J. A. & Fischer, J. E. Tumour necrosis factor (TNF) and interleukin-1 (IL-1) induce muscle proteolysis through different mechanisms. Mediators Inflamm 1, 247-250, doi:10.1155/S0962935192000371 (1992).
51 McClung, J. M., Judge, A. R., Talbert, E. E. & Powers, S. K. Calpain-1 is required for hydrogen peroxide-induced myotube atrophy. Am J Physiol Cell Physiol 296, C363-371, doi:10.1152/ajpcell.00497.2008 (2009).
52 Dodd, S. L., Gagnon, B. J., Senf, S. M., Hain, B. A. & Judge, A. R. Ros-mediated activation of NF-kappaB and Foxo during muscle disuse. Muscle Nerve 41, 110-113, doi:10.1002/mus.21526 (2010).
53 Smuder, A. J., Hudson, M. B., Nelson, W. B., Kavazis, A. N. & Powers, S. K. Nuclear factor-kappaB signaling contributes to mechanical ventilation-induced diaphragm weakness*. Crit Care Med 40, 927-934, doi:10.1097/CCM.0b013e3182374a84 (2012).
54 McClung, J. M., Judge, A. R., Powers, S. K. & Yan, Z. p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol 298, C542-549, doi:10.1152/ajpcell.00192.2009 (2010).
55 Miller, B. F., Robinson, M. M., Bruss, M. D., Hellerstein, M. & Hamilton, K. L. A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction. Aging Cell 11, 150-161, doi:10.1111/j.1474-9726.2011.00769.x (2012).
56 Conley, K. E., Jubrias, S. A. & Esselman, P. C. Oxidative capacity and ageing in human muscle. J Physiol 526 Pt 1, 203-210, doi:10.1111/j.1469-7793.2000.t01-1-00203.x (2000).
57 Swirski, F. K. et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325, 612-616, doi:10.1126/science.1175202 (2009).
58 Eftimie, R., Brenner, H. R. & Buonanno, A. Myogenin and MyoD join a family of skeletal muscle genes regulated by electrical activity. Proc Natl Acad Sci U S A 88, 1349-1353, doi:10.1073/pnas.88.4.1349 (1991).
59 Moresi, V. et al. Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell 143, 35-45, doi:10.1016/j.cell.2010.09.004 (2010).
60 Macpherson, P. C., Wang, X. & Goldman, D. Myogenin regulates denervation-dependent muscle atrophy in mouse soleus muscle. J Cell Biochem 112, 2149-2159, doi:10.1002/jcb.23136 (2011).
61 Ciciliot, S., Rossi, A. C., Dyar, K. A., Blaauw, B. & Schiaffino, S. Muscle type and fiber type specificity in muscle wasting. Int J Biochem Cell Biol 45, 2191-2199, doi:10.1016/j.biocel.2013.05.016 (2013).
62 Tian, M., Asp, M. L., Nishijima, Y. & Belury, M. A. Evidence for cardiac atrophic remodeling in cancer-induced cachexia in mice. Int J Oncol 39, 1321-1326, doi:10.3892/ijo.2011.1150 (2011).
63 Swynghedauw, B. Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles. Physiol Rev 66, 710-771, doi:10.1152/physrev.1986.66.3.710 (1986).

指導教授

陳盛良(Shen-Liang Chen)

審核日期

2024-7-23

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