進階搜尋


下載電子全文  
系統識別號 U0026-1208201320143800
論文名稱(中文) 活化雌性激素貝它對亞急性期心肌梗塞鼠心室功能之有限性改善
論文名稱(英文) Limited improvement of Activated Estrogen Receptor β on ventricular functions of infarcted rat hearts at the Sub-acute Phase
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 101
學期 2
出版年 102
研究生(中文) 王禹城
研究生(英文) Yu-Cheng Wang
學號 S36981109
學位類別 碩士
語文別 英文
論文頁數 95頁
口試委員 指導教授-蔡美玲
口試委員-洪麗滿
口試委員-甘宗旦
中文關鍵字 差異性蛋白質體  亞急性期心肌梗塞  代謝轉移  內質網壓力  棕梠酸  雌性激素貝它  內質網與粒線體連結  鈣離子調動  H9c2心肌原細胞 
英文關鍵字 comparative proteome  sub-acute phase of myocardial infarction  metabolism shift  endoplasmic reticulum stress  palmitic acid, estrogen receptor β  mitochondrial activity and calcium mobilization  H9c2 cardiomyoblast 
學科別分類
中文摘要 今日,對於降低心血管所造成的死亡率,研究減速心肌梗塞到心衰竭的過程是一個重要的課題。我們初步的研究顯示心肌梗塞後兩天到六周的亞急性期中有代謝轉移的現象。然而代謝轉移通常伴隨著內質網壓力並造成細胞的死亡。雌性激素貝它已知有引起心臟保護性。因為內質網與粒線體連結調控鈣離子的調動,在本研究中,我們利用差異性蛋白質體與常見的西方點墨法,探討活化雌性激素貝它是否藉由改變內質網與粒線體的連結去保護梗塞心臟。並利用長鏈脂肪酸棕梠酸處理的心肌原細胞H9c2 當作我們的離體實驗模型。心臟超音波分析顯示亞急性期心臟有功能上的損傷。長鏈脂肪酸去氫酵素與內質網壓力相關的存活蛋白干擾素可誘導雙鏈核糖核酸依賴蛋白激脢的心室蛋白表現量都下降並與部分縮時有正相關;相反的,細胞週期與凋亡相關蛋白和凋亡誘導因子都沒有改變。棕梠酸藉由增加內質網壓力相關凋亡蛋白CCAAT增強子結合蛋白同源蛋白去促進細胞死亡,而並不透過影響細胞週期與凋亡相關蛋白和凋亡誘導因子。每天腹腔注射雌性激素貝它增效劑DPN持續14天,顯示藉由增加收縮期左心室腔徑來改善心臟功能。此外,雌性激素貝它防止棕梠酸促進的細胞死亡,但並不改變死亡蛋白的表現量。蛋白質體數據顯示,DPN增加氧化磷酸化與鈣離子調動之相關蛋白的表現量。綜合結果,可以建議其活化雌性激素貝它具有潛在的影響去維持亞急性期的心臟功能,透過調控內質網與粒線體連結。未來在亞急性期心肌梗塞的內質網與粒線體連結的研究可以提供一個替代的路徑去防止心衰竭。
英文摘要 Today, the study of decelerating the progression of myocardial infarction (MI) to heart failure is an important issue to reduce cardiovascular mortality. Our first part study showed the metabolism shift during sub-acute phase which is the period 2 day- 6 week after MI. Endoplasmic reticulum stress is often accompanied with metabolism disorder and induces cell death. Estrogen receptor β (ER β) has been showed that elicits cardio-protections. Since endoplasmic reticulum -mitochondrial coupling modulates calcium mobilization, in this study, we investigated whether activation of ER β protects the infaracted hearts by changing the coupling between endoplasmic reticulum and mitochondria by using comparative proteome, conventional western blotting analysis. Long chain fatty acid palmitic acid (PA)-treated H9c2 (cardiomyoblasts) was used as our in vitro model. Echocardiographic analysis showed functional impairments in sub-acute infarcted hearts. Ventricular protein expression of long chain acyl-CoA dehydrogenase and endoplasmic reticulum stress-related survival protein double stranded RNA-dependent protein kinase were decreased and showed positive correlation with fractional shortening, while cell cycle and apoptosis related protein (CARP1) and apoptosis-induced factor (AIF) were not altered. PA induced cell death with increase of ER stress-related apoptotic protein CCAAT-enhancer-binding protein homologous protein not influences of CARP -1and AIF. Daily intraperitoneal administration with DPN (ER β agonist) for 14 days showed improvement on cardiac function with the increase of left ventricular internal diameter in the systolic phase. In addition, ER β prevented PA-induced cell death but did not change apoptotic protein expression. Proteomic data showed the enhanced expression of proteins related with oxidative phosphorylation and calcium mobilization by DPN. Taken together, these results suggest that ER β has potential effect to preserve cardiac function during the sub-acute phase of MI by modulating the endoplasmic reticulum -mitochondrial coupling. Further studies of the endoplasmic reticulum -mitochondrial coupling on sub-acute infracted hearts may provide an alternative pathway to prevent heart failure.
論文目次 中文摘要 I
Abstract III
誌謝 V
Index VI
List of tables XI
List of figures XII

Chapter I. Literature reviews

1. Epidemiological studies of cardiovascular diseases 1
2. Pathogenesis of heart failure after acute myocardial infarction. 1
3. Proteomic studies of myocardial infarction and heart failure 1

Chapter II. Specific introduction for Part I:

1. Proteomic analysis of infarcted hearts in the sub-acute phase 4
2. Proteomics-driven hypothesis: the change of lipid metabolism in the subacute myocardial infarction period induces endoplasmic reticulum (ER) stress and causes cell death 4

Chapter III. Materials and Methods for Parts I and II
I. In vivo study
1. Animal care 7
2. Myocardial infarction surgery 7
3. Echocardiography 7
4. Fatty acid quantification 8

II. In vitro study
1. Cell culture 9
2. Palmitic acid preparation 9
3. Trypan Blue Exclusion 9
4. MTT assay 10
5. Fow cytometry 10

III. Sample preparation
1. Tissue homogenization 10
2. Cell lysate 11

IV. Western blot and Proteomic analysis
1. Western blot analysis 11
2. In-gel protein digestion 12
3. Stable isotope dimethyl labeling 12
4. Mass spectrometry and protein identification 13
5. Quantitative analysis of dimethyl labeled peptides 14

V. Data analysis and statistical evaluation 15

Chapter IV. Results for Part I
1. Characterization of infarcted hearts in the sub-acute phase 16
2. Functional impairment of infarcted hearts in the sub-acute phase 16
3. Validation of cardiac proteins identified and quantified by quantitative proteomic analysis 17
4. Working hypothesis: the decreased amounts of long-chain acyl- CoA dehydrogenase causes endoplasmic reticulum (ER) stress in the infarcted hearts during the sub-acute phase 18
5. Palmitc aicd (PA)-induced cell death and ER stress in H9c2 cells 20

Chapter V. Specific introduction for Part II

1. Abnormal fatty acid metabolism in sub-acute phase of MI 22
2. Functional role of estrogen on abnormal fatty acid metabolism 22
3. Functional role of estrogen on anti-apoptosis after cardiac damage 23
4. Endoplasmic reticulum- mitochondrial coupling on muscle contraction and cell death 23
5. Working hypothesis: Cardio-protections of estrogen receptor β are due to the improvement of endoplamic reticulum-mitochondrial coupling which enhances contraction 24

Chapter VI. Results for Part II
1. Decrease of LVIDs by DPN in sub-acute infarcted hearts 26
2. DPN did not revered metabolism shift in sub-acute infarcted hearts 26
3. DPN did not lower endoplasmic reticulum stress in sub-acute infarcted hearts. 27
4. DPN did not reversed but partially prevented PA-induced cell death 28
Characterization of H9c2 cells 28
Preventive effect of DPN on PA-induced cell death 29
5. Preventive effect of estrogen receptor β is through modulating mitochondrial activity not decreasing expression of apoptotic protein. 29
6. Proteomic analysis reveals the possible protective roles of DPN in modulating ATP synthesis and calcium mobilization during sub-acute phase of myocardial infarction. 30

Chapter VII. Discussion for Parts I and II
1. Summarize important findings 32
2. Interpret findings & key literature supports
1. Inflammation in the sub-acute phase of myocardial infarction. 33
2. Lipid accumulation with the depression of sympathetic nerve activation in sub-acute phase of myocardial infarction 34
3. Hypoxia toxicity in the acute phase and lipotoxicity in the sub-acute phase of myocardial infarction 34
4. Changes of the metabolism pattern in sub-acute phase of myocardial infarction 35
5. Involvements of endoplasmic reticulum stress in sub-acute infarcted hearts and palmitic acid-induced cardiomyocyte death 36
6. Preventive effects of estrogen receptor β on long chain fatty acid-induced cell death 37
7. Contributions of estrogen receptor β to cardiac muscle contraction during the sub-acute phase 38
8. Cardioprotections of estrogen receptor β pre-exposure after myocardial infarction 39
9. Enzymes identified from proteome in fatty acid metabolism pathway 40

3. Significance of this study 42

Chapter VIII. References 44
Chapter IX. Tables 53
Chapter X. Figures 69
參考文獻 1. World Health Organization. (2008) The global burden of disease : 2004 update. Geneva: World Health Organization. 146 p. p.
2. World Health Organization. (2011) Global status report on noncommunicable diseases 2010. Geneva: World Health Organization. ix, 164 p. p.
3. Mendis S, Puska P, Norrving B, World Health Organization., World Heart Federation., et al. (2011) Global atlas on cardiovascular disease prevention and control. Geneva: World Health Organization. vi, 155 p. p.
4. Gheorghiade M, Ruzumna P, Borzak S, Havstad S, Ali A, et al. (1996) Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies. Am Heart J 131: 250-256.
5. Yusuf S, Reddy S, Ounpuu S, Anand S (2001) Global burden of cardiovascular diseases: Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 104: 2855-2864.
6. Botkin NF, Spencer FA, Goldberg RJ, Lessard D, Yarzebski J, et al. (2006) Changing trends in the long-term prognosis of patients with acute myocardial infarction: a population-based perspective. Am Heart J 151: 199-205.
7. Backenkohler U, Erdogan A, Steen-Mueller MK, Kuhlmann C, Most A, et al. (2005) Long-term incidence of malignant ventricular arrhythmia and shock therapy in patients with primary defibrillator implantation does not differ from event rates in patients treated for survived cardiac arrest. J Cardiovasc Electrophysiol 16: 478-482.
8. Erdman JW, Jr. (2000) AHA Science Advisory: Soy protein and cardiovascular disease: A statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation 102: 2555-2559.
9. Chen YC, Jin X, Zeng Z, Liu WQ, Wang B, et al. (2009) Estrogen-replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing SDF-1 and estrogen receptor expression. Microvascular Research 77: 71-77.
10. Welt FG, Gallegos R, Connell J, Kajstura J, D'Amario D, et al. (2013) Effect of cardiac stem cells on left-ventricular remodeling in a canine model of chronic myocardial infarction. Circ Heart Fail 6: 99-106.
11. Xiang YK (2011) Compartmentalization of beta-adrenergic signals in cardiomyocytes. Circ Res 109: 231-244.
12. Parrish DC, Alston EN, Rohrer H, Nkadi P, Woodward WR, et al. (2010) Infarction-induced cytokines cause local depletion of tyrosine hydroxylase in cardiac sympathetic nerves. Experimental Physiology 95: 304-314.
13. De Gennaro L, Brunetti ND, Montrone D, De Rosa F, Cuculo A, et al. (2012) Subacute Inflammatory Activation in Subjects with Acute Coronary Syndrome and Left Ventricular Dysfunction. Inflammation 35: 363-370.
14. De Celle T, Vanrobaeys F, Lijnen P, Blankesteijn WM, Heeneman S, et al. (2005) Alterations in mouse cardiac proteome after in vivo myocardial infarction: permanent ischaemia versus ischaemia-reperfusion. Experimental Physiology 90: 593-606.
15. Chu G, Egnaczyk GF, Zhao W, Jo SH, Fan GC, et al. (2004) Phosphoproteome analysis of cardiomyocytes subjected to beta-adrenergic stimulation: identification and characterization of a cardiac heat shock protein p20. Circ Res 94: 184-193.
16. Petrak J, Pospisilova J, Sedinova M, Jedelsky P, Lorkova L, et al. (2011) Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2. Proteome Sci 9: 69.
17. Edwards AV, White MY, Cordwell SJ (2008) The role of proteomics in clinical cardiovascular biomarker discovery. Mol Cell Proteomics 7: 1824-1837.
18. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, et al. (2006) Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312: 734-737.
19. Cox KB, Liu J, Tian L, Barnes S, Yang Q, et al. (2009) Cardiac hypertrophy in mice with long-chain acyl-CoA dehydrogenase or very long-chain acyl-CoA dehydrogenase deficiency. Lab Invest 89: 1348-1354.
20. Bakermans AJ, Geraedts TR, van Weeghel M, Denis S, Ferraz MJ, et al. (2011) Fasting-Induced Myocardial Lipid Accumulation in Long-Chain Acyl-CoA Dehydrogenase Knockout Mice Is Accompanied by Impaired Left Ventricular Function. Circulation-Cardiovascular Imaging 4: 558-565.
21. Cox KB, Hamm DA, Millington DS, Matern D, Vockley J, et al. (2001) Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Human Molecular Genetics 10: 2069-2077.
22. Zhang DY, Liu ZX, Choi CS, Tian LQ, Kibbey R, et al. (2007) Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proceedings of the National Academy of Sciences of the United States of America 104: 17075-17080.
23. Malhi H, Gores GJ (2008) Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease. Seminars in Liver Disease 28: 360-369.
24. Trauner M, Arrese M, Wagner M (2010) Fatty liver and lipotoxicity. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 1801: 299-310.
25. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, et al. (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397: 441-446.
26. Millott R, Dudek E, Michalak M (2012) The endoplasmic reticulum in cardiovascular health and disease. Can J Physiol Pharmacol 90: 1209-1217.
27. Gentile CL, Frye M, Pagliassotti MJ (2011) Endoplasmic Reticulum Stress and the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease. Antioxidants & Redox Signaling 15: 505-521.
28. Malhi H, Kaufman RJ (2011) Endoplasmic reticulum stress in liver disease. Journal of Hepatology 54: 795-809.
29. Pagliassotti MJ (2012) Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease. Annual Review of Nutrition, Vol 32 32: 17-+.
30. Gotoh T, Terada K, Oyadomari S, Mori M (2004) Hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death and Differentiation 11: 390-402.
31. Gunstone FD, Harwood JL, Dijkstra AJ (2007) The lipid handbook with CD-ROM. Boca Raton: CRC Press. xiii, 656 p. p.
32. Plaisance V, Perret V, Favre D, Abderrahmani A, Yang JY, et al. (2009) Role of the transcriptional factor C/EBPbeta in free fatty acid-elicited beta-cell failure. Mol Cell Endocrinol 305: 47-55.
33. Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE (2009) Diabetes and apoptosis: lipotoxicity. Apoptosis 14: 1484-1495.
34. Yuzefovych L, Wilson G, Rachek L (2010) Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress. Am J Physiol Endocrinol Metab 299: E1096-1105.
35. Zhang Y, Yang X, Shi H, Dong L, Bai J (2011) Effect of alpha-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes. Lipids Health Dis 10: 122.
36. Listenberger LL, Ory DS, Schaffer JE (2001) Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J Biol Chem 276: 14890-14895.
37. Tang MJ, Hu JJ, Lin HH, Chiu WT, Jiang ST (1998) Collagen gel overlay induces apoptosis of polarized cells in cultures: disoriented cell death. Am J Physiol 275: C921-931.
38. Catts VS, Catts SV, McGrath JJ, Feron F, McLean D, et al. (2006) Apoptosis and schizophrenia: a pilot study based on dermal fibroblast cell lines. Schizophr Res 84: 20-28.
39. Cleutjens JP, Kandala JC, Guarda E, Guntaka RV, Weber KT (1995) Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol 27: 1281-1292.
40. Sutton MG, Sharpe N (2000) Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101: 2981-2988.
41. Zhao WY, Zhao D, Yan R, Sun Y (2009) Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase. Cardiovascular Pathology 18: 156-166.
42. Lam SY, Liu Y, Ng KM, Lau CF, Liong EC, et al. (2012) Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways. Histochemistry and Cell Biology 137: 303-317.
43. Bhandary B, Marahatta A, Kim HR, Chae HJ (2013) An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases. International Journal of Molecular Sciences 14: 434-456.
44. Barger PM, Kelly DP (1999) Fatty acid utilization in the hypertrophied and failing heart: molecular regulatory mechanisms. Am J Med Sci 318: 36-42.
45. Brinkmann JF, Abumrad NA, Ibrahimi A, van der Vusse GJ, Glatz JF (2002) New insights into long-chain fatty acid uptake by heart muscle: a crucial role for fatty acid translocase/CD36. Biochem J 367: 561-570.
46. Basseri S, Austin RC (2012) Endoplasmic reticulum stress and lipid metabolism: mechanisms and therapeutic potential. Biochem Res Int 2012: 841362.
47. Xu J, Zhou Q, Xu W, Cai L (2012) Endoplasmic reticulum stress and diabetic cardiomyopathy. Exp Diabetes Res 2012: 827971.
48. Nakamura T, Furuhashi M, Li P, Cao HM, Tuncman G, et al. (2010) Double-Stranded RNA-Dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell 140: 338-U341.
49. Donze O, Deng J, Curran J, Sladek R, Picard D, et al. (2004) The protein kinase PKR: a molecular clock that sequentially activates survival and death programs. Embo Journal 23: 564-571.
50. Srivastava SP, Davies MV, Kaufman RJ (1995) Calcium Depletion from the Endoplasmic-Reticulum Activates the Double-Stranded Rna-Dependent Protein-Kinase (Pkr) to Inhibit Protein-Synthesis. Journal of Biological Chemistry 270: 16619-16624.
51. Thomas D, Kim HY, Morgan R, Hanley MR (1998) Double-stranded-RNA-activated protein kinase (PKR) regulates Ca2+ stores in Xenopus oocytes. Biochemical Journal 330: 599-603.
52. Rishi AK, Zhang L, Boyanapalli M, Wali A, Mohammad RM, et al. (2003) Identification and characterization of a cell cycle and apoptosis regulatory protein-1 as a novel mediator of apoptosis signaling by retinoid CD437. J Biol Chem 278: 33422-33435.
53. Cande C, Cohen I, Daugas E, Ravagnan L, Larochette N, et al. (2002) Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. Biochimie 84: 215-222.
54. Cande C, Vahsen N, Garrido C, Kroemer G (2004) Apoptosis-inducing factor (AIF): caspase-independent after all. Cell Death and Differentiation 11: 591-595.
55. Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22: 8608-8618.
56. Belanger AJ, Luo Z, Vincent KA, Akita GY, Cheng SH, et al. (2007) Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor alpha/retinoid X receptor. Biochem Biophys Res Commun 364: 567-572.
57. Perman JC, Bostrom P, Lindbom M, Lidberg U, StAhlman M, et al. (2011) The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction. J Clin Invest 121: 2625-2640.
58. Mendelsohn ME (2002) Protective effects of estrogen on the cardiovascular system. Am J Cardiol 89: 12E-17E; discussion 17E-18E.
59. van Eickels M, Grohe C, Cleutjens JP, Janssen BJ, Wellens HJ, et al. (2001) 17beta-estradiol attenuates the development of pressure-overload hypertrophy. Circulation 104: 1419-1423.
60. Newton KM, LaCroix AZ, McKnight B, Knopp RH, Siscovick DS, et al. (1997) Estrogen replacement therapy and prognosis after first myocardial infarction. Am J Epidemiol 145: 269-277.
61. Shlipak MG, Angeja BG, Go AS, Frederick PD, Canto JG, et al. (2001) Hormone therapy and in-hospital survival after myocardial infarction in postmenopausal women. Circulation 104: 2300-2304.
62. Krasinski K, Spyridopoulos I, Asahara T, van der Zee R, Isner JM, et al. (1997) Estradiol accelerates functional endothelial recovery after arterial injury. Circulation 95: 1768-1772.
63. Arnal JF, Fontaine C, Billon-Gales A, Favre J, Laurell H, et al. (2010) Estrogen receptors and endothelium. Arterioscler Thromb Vasc Biol 30: 1506-1512.
64. Pelzer T, Loza PA, Hu K, Bayer B, Dienesch C, et al. (2005) Increased mortality and aggravation of heart failure in estrogen receptor-beta knockout mice after myocardial infarction. Circulation 111: 1492-1498.
65. Jazbutyte V, Arias-Loza PA, Hu K, Widder J, Govindaraj V, et al. (2008) Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats. Cardiovasc Res 77: 774-781.
66. Pelzer T, Schumann M, Neumann M, deJager T, Stimpel M, et al. (2000) 17beta-estradiol prevents programmed cell death in cardiac myocytes. Biochem Biophys Res Commun 268: 192-200.
67. Kim JK, Pedram A, Razandi M, Levin ER (2006) Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms. J Biol Chem 281: 6760-6767.
68. Liu CJ, Lo JF, Kuo CH, Chu CH, Chen LM, et al. (2009) Akt mediates 17beta-estradiol and/or estrogen receptor-alpha inhibition of LPS-induced tumor necresis factor-alpha expression and myocardial cell apoptosis by suppressing the JNK1/2-NFkappaB pathway. J Cell Mol Med 13: 3655-3667.
69. Cao J, Zhu T, Lu L, Geng L, Wang L, et al. (2011) Estrogen induces cardioprotection in male C57BL/6J mice after acute myocardial infarction via decreased activity of matrix metalloproteinase-9 and increased Akt-Bcl-2 anti-apoptotic signaling. Int J Mol Med 28: 231-237.
70. Wang M, Wang Y, Weil B, Abarbanell A, Herrmann J, et al. (2009) Estrogen receptor beta mediates increased activation of PI3K/Akt signaling and improved myocardial function in female hearts following acute ischemia. Am J Physiol Regul Integr Comp Physiol 296: R972-978.
71. Bakowski D, Nelson C, Parekh AB (2012) Endoplasmic reticulum-mitochondria coupling: local Ca2+ signalling with functional consequences. Pflugers Archiv-European Journal of Physiology 464: 27-32.
72. Leemand J, Koh EH (2012) Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus. Experimental Diabetes Research.
73. Vamecq J, Dessein AF, Fontaine M, Briand G, Porchet N, et al. (2012) Mitochondrial dysfunction and lipid homeostasis. Curr Drug Metab 13: 1388-1400.
74. Viola HM, Hool LC (2010) Cross-talk between L-type Ca2+ channels and mitochondria. Clin Exp Pharmacol Physiol 37: 229-235.
75. Stirone C, Duckles SP, Krause DN, Procaccio V (2005) Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Mol Pharmacol 68: 959-965.
76. Yang SH, Liu R, Perez EJ, Wen Y, Stevens SM, Jr., et al. (2004) Mitochondrial localization of estrogen receptor beta. Proc Natl Acad Sci U S A 101: 4130-4135.
77. Yang SH, Sarkar SN, Liu R, Perez EJ, Wang X, et al. (2009) Estrogen receptor beta as a mitochondrial vulnerability factor. J Biol Chem 284: 9540-9548.
78. Yang X, Chen G, Papp R, Defranco DB, Zeng F, et al. (2012) Oestrogen upregulates L-type Ca(2)(+) channels via oestrogen-receptor- by a regional genomic mechanism in female rabbit hearts. J Physiol 590: 493-508.
79. Tian GX, Sun Y, Pang CJ, Tan AH, Gao Y, et al. (2012) Oestradiol is a protective factor for non-alcoholic fatty liver disease in healthy men. Obes Rev 13: 381-387.
80. Shimizu I, Ito S (2007) Protection of estrogens against the progression of chronic liver disease. Hepatol Res 37: 239-247.
81. Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115: 2656-2664.
82. Grott M, Karakaya S, Mayer F, Baertling F, Beyer C, et al. (2013) Progesterone and estrogen prevent cisplatin-induced apoptosis of lung cancer cells. Anticancer Res 33: 791-800.
83. Sribnick EA, Ray SK, Banik NL (2006) Estrogen prevents glutamate-induced apoptosis in C6 glioma cells by a receptor-mediated mechanism. Neuroscience 137: 197-209.
84. Nilsen J, Chen S, Irwin RW, Iwamoto S, Brinton RD (2006) Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function. BMC Neurosci 7: 74.
85. Klinge CM (2008) Estrogenic control of mitochondrial function and biogenesis. J Cell Biochem 105: 1342-1351.
86. Viola HM, Davies SM, Filipovska A, Hool LC (2013) L-type Ca(2+) channel contributes to alterations in mitochondrial calcium handling in the mdx ventricular myocyte. Am J Physiol Heart Circ Physiol 304: H767-775.
87. Bodi I, Mikala G, Koch SE, Akhter SA, Schwartz A (2005) The L-type calcium channel in the heart: the beat goes on. J Clin Invest 115: 3306-3317.
88. Sanchez JA, Garcia MC, Sharma VK, Young KC, Matlib MA, et al. (2001) Mitochondria regulate inactivation of L-type Ca2+ channels in rat heart. J Physiol 536: 387-396.
89. Frank KF, Bolck B, Erdmann E, Schwinger RH (2003) Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation. Cardiovasc Res 57: 20-27.
90. Prestle J, Quinn FR, Smith GL (2003) Ca(2+)-handling proteins and heart failure: novel molecular targets? Curr Med Chem 10: 967-981.
91. Fuchs M, Hilfiker A, Kaminski K, Hilfiker-Kleiner D, Guener Z, et al. (2003) Role of interleukin-6 for LV remodeling and survival after experimental myocardial infarction. FASEB J 17: 2118-2120.
92. Fuchs M, Hilfiker A, Kaminski K, Hilfiker-Kleiner D, Guener Z, et al. (2003) Role of interleukin-6 for LV remodeling and survival after experimental myocardial infarction. Faseb Journal 17: 2118-2120.
93. Hom GJ, Forrest MJ, Bach TJ, Brady E, Candelore MR, et al. (2001) Beta(3)-adrenoceptor agonist-induced increases in lipolysis, metabolic rate, facial flushing, and reflex tachycardia in anesthetized rhesus monkeys. J Pharmacol Exp Ther 297: 299-307.
94. Tavernier G, Jimenez M, Giacobino JP, Hulo N, Lafontan M, et al. (2005) Norepinephrine induces lipolysis in beta(1)/beta(2)/beta(3)-adrenoceptor knockout mice. Molecular Pharmacology 68: 793-799.
95. Meraihi Z, Lutz O, Scheftel JM, Frey A, Ferezou J, et al. (1991) Decreased lipolytic activity in tissues during infectious and inflammatory stress. Nutrition 7: 93-97; discussion 98.
96. Ma KL, Ruan XZ, Powis SH, Chen Y, Moorhead JF, et al. (2008) Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology 48: 770-781.
97. Borisov AB, Ushakov AV, Zagorulko AK, Novikov NY, Selivanova KF, et al. (2008) Intracardiac lipid accumulation, lipoatrophy of muscle cells and expansion of myocardial infarction in type 2 diabetic patients. Micron 39: 944-951.
98. Goldfarb JW, Roth M, Han J (2009) Myocardial fat deposition after left ventricular myocardial infarction: assessment by using MR water-fat separation imaging. Radiology 253: 65-73.
99. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7: 11-20.
100. Rennison JH, McElfresh TA, Okere IC, Patel HV, Foster AB, et al. (2008) Enhanced acyl-CoA dehydrogenase activity is associated with improved mitochondrial and contractile function in heart failure. Cardiovascular Research 79: 331-340.
101. Patten RD, Pourati I, Aronovitz MJ, Baur J, Celestin F, et al. (2004) 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res 95: 692-699.
102. Schrauwen-Hinderling VB, Roden M, Kooi ME, Hesselink MK, Schrauwen P (2007) Muscular mitochondrial dysfunction and type 2 diabetes mellitus. Curr Opin Clin Nutr Metab Care 10: 698-703.
103. Henique C, Mansouri A, Fumey G, Lenoir V, Girard J, et al. (2010) Increased mitochondrial fatty acid oxidation is sufficient to protect skeletal muscle cells from palmitate-induced apoptosis. J Biol Chem 285: 36818-36827.
104. Zhang H, Liu YW, Wang L, Li Z, Zhang HW, et al. (2013) Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat. Journal of Lipid Research 54: 345-357.
105. Schaible TF, Malhotra A, Ciambrone G, Scheuer J (1984) The Effects of Gonadectomy on Left-Ventricular Function and Cardiac Contractile Proteins in Male and Female Rats. Circulation Research 54: 38-49.
106. Scheuer J, Malhotra A, Schaible TF, Capasso J (1987) Effects of Gonadectomy and Hormonal Replacement on Rat Hearts. Circulation Research 61: 12-19.
107. Wu TW, Wang JM, Chen S, Brinton RD (2005) 17 beta-Estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-amp response element binding protein signal pathway and Bcl-2 expression in rat hippocampal neurons: A potential initiation mechanism for estrogen-induced neuroprotection. Neuroscience 135: 59-72.
108. Capasso JM, Remily RM, Smith RH, Sonnenblick EH (1983) Sex-Differences in Myocardial-Contractility in the Rat. Basic Research in Cardiology 78: 156-171.
109. Zhan E, Keimig T, Xu J, Peterson E, Ding J, et al. (2008) Dose-dependent cardiac effect of oestrogen replacement in mice post-myocardial infarction. Experimental Physiology 93: 982-993.
110. Warner MM, Guo J, Zhao Y (2001) The relationship between plasma apolipoprotein A-IV levels and coronary heart disease. Chin Med J (Engl) 114: 275-279.
111. Kleine AH, Glatz JF, Van Nieuwenhoven FA, Van der Vusse GJ (1992) Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man. Mol Cell Biochem 116: 155-162.
112. Glatz JFC, vanderVusse GJ (1996) Cellular fatty acid-binding proteins: Their function and physiological significance. Progress in Lipid Research 35: 243-282.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2016-08-16起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2016-08-16起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw