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研究生:李孟翰
研究生(外文):Mong-Han Li
論文名稱:合成之咖啡酸衍生物36-12對心肌細胞在氧化壓力下保護作用之探討
論文名稱(外文):The Protective Effects and Underlying Mechanisms of a New Synthetic Derivative of Caffeic Acid on Cardiomyocytes under Oxidative Stress
指導教授:蘇銘嘉
指導教授(外文):Ming-Jai Su
口試委員:陳文彬李安生
口試委員(外文):Wen-Pin ChenAn-Sheng Lee
口試日期:2014-07-28
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:62
中文關鍵詞:氧化壓力咖啡酸STAT3抗氧化心臟保護
外文關鍵詞:oxidative stresscaffeic acidSTAT3ROS scavengingcardioprotection
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背景: 缺血性心臟病是常見的心血管疾病之一。當心肌缺血時,及早恢復血流供應在治療上是十分迫切的。然而,伴隨而來的再灌流損傷卻可能對心臟造成進一步的傷害,且至今仍無公認的治療準則問世。研究顯示,咖啡酸及其衍生物在心臟保護及抗氧化上皆有顯著的效果。本論文欲探討咖啡酸衍生物,compound 36-12,對於心肌細胞在氧化壓力下的保護效果,及其作用機制。

方法及結果: 本實驗使用50 μM的H2O2對H9c2細胞株所造成之氧化壓力,模擬再灌流對於心臟之傷害。首先,使用MTT試驗評估compound 36-12之保護能力,並與抗氧化劑NAC之效果做對照。同時,藉由螢光探針測量細胞中ROS的含量,以評估藥物的抗氧化效果。此外,也進一步使用蛋白抑制劑阻斷心臟保護相關蛋白之活性,以探討其作用機轉。最後,使用西方墨點法觀察氧化壓力下這些蛋白的活化情形,以及compound 36-12對其造成之影響。實驗結果發現在氧化壓力下,3 μM的compound 36-12即可產生顯著的心臟保護、及抗氧化效果,其程度和50 μM的NAC類似。透過蛋白抑制劑的使用,發現在抑制STAT3的情況下,compound 36-12的保護效果幾乎完全消失。至於其抗氧化作用雖被部分抑制,但仍能顯著降低ROS的生成量。而抑制JAK2之活性,則可提升氧化壓力下的細胞存活率,並降低ROS的生成量。藉由西方墨點法,發現compound 36-12不僅可顯著增加STAT3及AMPK之磷酸化、減少ERK磷酸化,也明顯降低了氧化壓力初期eNOS及JAK2的磷酸化程度。

結論: 在氧化壓力下,compound 36-12可大幅降低心肌細胞中ROS的生成量,並顯著提升了細胞存活率。此效果可能和對STAT3磷酸化之促進,以及對氧化壓力引起之JAK2磷酸化的抑制有關。而其對於STAT3磷酸化之促進效果,應非藉由JAK2而達成。


Background: Ischemic heart disease is one of the most prevalent cardiovascular problems in the world. Once ischemia occurs, restoration of blood flow as soon as possible is necessary for minimizing the damage to the least. However, reperfusion injury may even lead to more horrible outcome to the heart. As far, there is still no guideline for treatment of reperfusion injury. Caffeic acid is recognized as a good antioxidant and proved beneficial for cardioprotection by previous works. In this study, we try to figure out whether a synthetic caffeic acid derivative, compound 36-12, has cardioprotective effects under oxidative stress, and investigate the underlying mechanisms as well.

Methods and Results: In this study, 50 μM H2O2 was used to induce oxidative stress in H9c2 cell line to mimic myocardial reperfusion injury. Firstly, we examined the protective effect of compound 36-12 by MTT assay, and compared it with NAC, a well-known antioxidant. Secondly, we measured intracellular ROS level by fluorescent probes to observe antioxidant activity of the drug. Besides, we also used different protein inhibitors to block signaling pathways which make contribution to cardioprotection, and then observed whether the protective effects of compound 36-12 was influenced by doing so. Lastly, activation extents of these proteins at different time points under oxidative stress were shown by Western blotting. Results showed that 3 μM compound 36-12 not only enhanced cell viability but also reduced intracellular ROS level under oxidative stress significantly. This protective effect was comparable to 50 μM NAC. Then, we found that the protective effect of compound 36-12 was totally abolished by STAT3 inhibition, and its ROS scavenging activity was attenuated as well. On the other hand, JAK2 inhibition could enhance cell viability and lower intracellular ROS level under oxidative stress. The results by Western blotting showed that compound 36-12 provoked STAT3 and AMPK phosphorylation obviously. At the same time, however, it also diminished the phosphorylation extent of ERK, as well as H2O2-induced phosphorylation of eNOS and JAK2.

Conclusion: Compound 36-12 shows marvelously cardioprotective and ROS scavenging effects under oxidative stress, which have something to do with activation of STAT3 and inhibition of JAK2. Besides, the phosphorylation of STAT3 induced by compound 36-12, is through a JAK2-independent mechanism.


目錄
口試委員審定書............................................Ⅰ
縮寫表....................................................Ⅱ
中文摘要..................................................Ⅲ
英文摘要..................................................Ⅳ
目錄......................................................Ⅵ
圖表目錄..................................................Ⅸ
第一章 緒論...............................................1
1.1 缺血性心臟病.......................................1
1.2 再灌流損傷.........................................2
1.2.1 代謝功能的異常.....................................3
1.2.2 離子調節的失衡.....................................4
1.2.3 氧化壓力的影響.....................................7
1.2.4 發炎反應的產生.....................................8
1.3 針對心臟缺血/ 再灌流之保護機制....................10
1.3.1 Cardiac conditioning及RISK、SAFE pathway..........10
1.3.2 AMPK之活化........................................13
1.3.3 抗氧化劑之應用....................................14
1.4 咖啡酸衍生物之相關研究............................14
1.5 實驗目的..........................................17
第二章 實驗材料及方法....................................18
2.1 實驗材料..............................................18
2.2 實驗方法..............................................19
2.2.1 H9c2細胞株培養.....................................19
2.2.2 細胞模擬再灌流模式.................................20
2.2.3 MTT細胞存活率測定..................................20
2.2.4 全細胞蛋白質萃取...................................22
2.2.5 蛋白質濃度測定及定量...............................22
2.2.6 西方墨點法.........................................23
2.2.7 ROS測定............................................24
2.2.7.1 螢光顯微鏡觀察..................................25
2.2.7.2 分光光度計定量..................................25
2.2.8 實驗數據分析與統計.................................26
第三章 實驗結果..........................................27
3.1 不同濃度之H2O2對於心肌細胞存活率的影響................27
3.2 預先給予Compound 36-12可減少H2O2所引起之心肌細胞死亡..27
3.3 抑制不同蛋白對於細胞存活率的影響......................28
3.4 Compound 36-12可抑制ROS的生成.........................29
3.5 抑制STAT3和JAK2對於ROS的影響..........................30
3.6 氧化壓力下不同蛋白的活化情形..........................30
第四章 討論..............................................47
4.1 Compound 36-12可顯著提升氧化壓力下之心肌細胞存活率....47
4.2 Compound 36-12的心臟保護作用,和Akt、NOS、AMPK等蛋白之活化無直接相關..............................................48
4.3 抑制ERK活性,可提升氧化壓力下細胞存活率...............48
4.4 Compound 36-12之保護效果,和STAT3之活化有關...........49
4.5 抑制JAK2活性,有助於氧化壓力下之細胞存活..............50
4.6 Compound 36-12具顯著抗氧化效果,而此效果部分來自於STAT3之活化....................................................50
4.7 抑制JAK2活性,可降低ROS之生成.........................51
4.8 Compound 36-12可降低氧化壓力所引起之eNOS、JAK2磷酸化..52
4.9 Compound 36-12對Akt及ERK磷酸化之影響..................52
4.10 Compound 36-12可大幅增加STAT3之磷酸化,而此作用並非透過JAK2之磷酸化達成..........................................53
4.11 Compound 36-12可降低氧化壓力初期引起之AMPK磷酸化。而在較長作用時間下,則可顯著增加AMPK磷酸化....................53
第五章 結論與展望........................................55
第六章 參考文獻..........................................56

圖表目錄
Table 1-1. Projections of Crude CVD Prevalence (%), 2010–2030 in the United States................................1
Figure 1-1. Mechanism of reperfusion injury................3
Figure 1-2. Ion flux in (A) normoxia, (B) ischemia, and (C) reperfusion state..........................................4
Figure 1-3. The consequence of mPTP opening................6
Figure 1-4. Formation and scavenging pathway of free radicals...................................................8
Figure 1-5. Mechanism of ischemia/ reperfusion (IR)-induced inflammation..............................................10
Figure 1-6. Protective pathway activated by cardiac conditioning..............................................11
Figure 1-7. Signal transduction in RISK pathway...........12
Figure 1-8. Classification of phenolic compounds..........15
Figure 1-9. Structure of caffeic acid phenethyl ester.....15
Figure 1-10. Anti-inflammatory targets for CAPE...........16
Figure 1-11. Structure of compound 36-12..................17
Figure 2-1. Time course of the experiment.................20
Figure 2-2. Mechanism of MTT assay........................21
Figure 3-1. Effect of H2O2 on cell viability..............33
Figure 3-2. Effects of compound 36-12 (A) and NAC (B) on cell viability............................................34
Figure 3-3. Effects of protein inhibitors on cell viability under oxidative stress in the presence or absence of compound 36-12............................................35
Figure 3-4. Effects of compound 36-12 or NAC on intracellular ROS and superoxide scavenging..............37
Figure 3-5. Effects of protein inhibitors on intracellular ROS (A) and superoxide (B) scavenging.....................39
Figure 3-6. The extent of protein phosphorylation under oxidative stress at different time points, in the presence or absence of compound 36-12 or NAC pretreatment..........40




Alpert, J. S., K. Thygesen, E. Antman and J. P. Bassand (2000). "Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction." J Am Coll Cardiol 36(3): 959-969.
Andreka, G., M. Vertesaljai, G. Szantho, G. Font, Z. Piroth, G. Fontos, E. D. Juhasz, L. Szekely, Z. Szelid, M. S. Turner, H. Ashrafian, M. P. Frenneaux and P. Andreka (2007). "Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs." Heart 93(6): 749-752.
Antoniak, S., R. Pawlinski and N. Mackman (2011). "Protease-activated receptors and myocardial infarction." IUBMB Life 63(6): 383-389.
Bainey, K. R. and P. W. Armstrong (2014). "Clinical perspectives on reperfusion injury in acute myocardial infarction." Am Heart J 167(5): 637-645.
Bell, J. R., K. M. Mellor, A. C. Wollermann and L. M. Delbridge (2011). "Cardiac ischaemic stress: cardiomyocyte Ca(2)(+), sex and sex steroids." Clin Exp Pharmacol Physiol 38(10): 717-723.
Belosjorow, S., R. Schulz, H. Dorge, F. U. Schade and G. Heusch (1999). "Endotoxin and ischemic preconditioning: TNF-alpha concentration and myocardial infarct development in rabbits." Am J Physiol 277(6 Pt 2): H2470-2475.
Besse, S., A. L. Bulteau, F. Boucher, B. Riou, B. Swynghedauw and J. de Leiris (2006). "Antioxidant treatment prevents cardiac protein oxidation after ischemia-reperfusion and improves myocardial function and coronary perfusion in senescent hearts." J Physiol Pharmacol 57(4): 541-552.
Bezerra, R. M., L. F. Veiga, A. C. Caetano, P. L. Rosalen, M. E. Amaral, A. C. Palanch and S. M. de Alencar (2012). "Caffeic acid phenethyl ester reduces the activation of the nuclear factor kappaB pathway by high-fat diet-induced obesity in mice." Metabolism 61(11): 1606-1614.
Bharti, A. C. and B. B. Aggarwal (2002). "Nuclear factor-kappa B and cancer: its role in prevention and therapy." Biochem Pharmacol 64(5-6): 883-888.
Buja, L. M. (2005). "Myocardial ischemia and reperfusion injury." Cardiovasc Pathol 14(4): 170-175.
Bulkely, B. H. and G. M. Hutchins (1977). "Myocardial consequences of coronary artery bypass graft surgery. The paradox of necrosis in areas of revascularization." Circulation 56(6): 906-913.
Cagnol, S. and J. C. Chambard (2010). "ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence." Febs j 277(1): 2-21.
Chang, G. J., C. J. Chang, W. J. Chen, Y. H. Yeh and H. Y. Lee (2013). "Electrophysiological and mechanical effects of caffeic acid phenethyl ester, a novel cardioprotective agent with antiarrhythmic activity, in guinea-pig heart." Eur J Pharmacol 702(1-3): 194-207.
Chen-Scarabelli, C., L. Saravolatz Ii, R. McCaukey, G. Scarabelli, J. Di Rezze, B. Mohanty, S. Barry, D. Latchman, V. Georgiadis, J. McCormick, L. Saravolatz, R. Knight, G. Faggian, J. Narula, A. Stephanou and T. M. Scarabelli (2013). "The cardioprotective effects of urocortin are mediated via activation of the Src tyrosine kinase-STAT3 pathway." Jakstat 2(3): e24812.
Chen, J. H. and C.-T. Ho (1997). "Antioxidant Activities of Caffeic Acid and Its Related Hydroxycinnamic Acid Compounds." Journal of Agricultural and Food Chemistry 45(7): 2374-2378.
Chen, M., H. He, S. Zhan, S. Krajewski, J. C. Reed and R. A. Gottlieb (2001). "Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion." J Biol Chem 276(33): 30724-30728.
Crompton, M. (1999). "The mitochondrial permeability transition pore and its role in cell death." Biochem J 341 ( Pt 2): 233-249.
De Minicis, S., E. Seki, C. Oesterreicher, B. Schnabl, R. F. Schwabe and D. A. Brenner (2008). "Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells." Hepatology 48(6): 2016-2026.
Djamali, A. (2007). "Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts." Am J Physiol Renal Physiol 293(2): F445-455.
Gaskin, F. S., K. Kamada, M. Yusof and R. J. Korthuis (2007). "5''-AMP-activated protein kinase activation prevents postischemic leukocyte-endothelial cell adhesive interactions." Am J Physiol Heart Circ Physiol 292(1): H326-332.
Grunberger, D., R. Banerjee, K. Eisinger, E. M. Oltz, L. Efros, M. Caldwell, V. Estevez and K. Nakanishi (1988). "Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis." Experientia 44(3): 230-232.
Halestrap, A. (2005). "Biochemistry: a pore way to die." Nature 434(7033): 578-579.
Halestrap, A. P. and C. Brenner (2003). "The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death." Curr Med Chem 10(16): 1507-1525.
Halestrap, A. P., S. J. Clarke and S. A. Javadov (2004). "Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection." Cardiovasc Res 61(3): 372-385.
He, W. H., B. Li, X. Zhu, K. H. Zhang, B. M. Li, Z. J. Liu, G. Y. Liu and J. Wang (2010). "[The role and mechanism of NADPH oxidase in leptin-induced reactive oxygen species production in hepatic stellate cells]." Zhonghua Gan Zang Bing Za Zhi 18(11): 849-854.
Heidenreich, P. A., J. G. Trogdon, O. A. Khavjou, J. Butler, K. Dracup, M. D. Ezekowitz, E. A. Finkelstein, Y. Hong, S. C. Johnston, A. Khera, D. M. Lloyd-Jones, S. A. Nelson, G. Nichol, D. Orenstein, P. W. Wilson and Y. J. Woo (2011). "Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association." Circulation 123(8): 933-944.
Heusch, G., J. Musiolik, N. Gedik and A. Skyschally (2011). "Mitochondrial STAT3 activation and cardioprotection by ischemic postconditioning in pigs with regional myocardial ischemia/reperfusion." Circ Res 109(11): 1302-1308.
Hilfiker-Kleiner, D., A. Hilfiker, M. Fuchs, K. Kaminski, A. Schaefer, B. Schieffer, A. Hillmer, A. Schmiedl, Z. Ding, E. Podewski, E. Podewski, V. Poli, M. D. Schneider, R. Schulz, J. K. Park, K. C. Wollert and H. Drexler (2004). "Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition, and heart protection from ischemic injury." Circ Res 95(2): 187-195.
Ince, H., E. Kandemir, C. Bagci, M. Gulec and O. Akyol (2006). "The effect of caffeic acid phenethyl ester on short-term acute myocardial ischemia." Med Sci Monit 12(5): Br187-193.
Jaeschke, H. and B. L. Woolbright (2012). "Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species." Transplant Rev (Orlando) 26(2): 103-114.
Jennings, R. B., H. M. Sommers, G. A. Smyth, H. A. Flack and H. Linn (1960). "Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog." Arch Pathol 70: 68-78.
Juman, S., N. Yasui, K. Ikeda, A. Ueda, M. Sakanaka, H. Negishi and T. Miki (2012). "Caffeic acid phenethyl ester suppresses the production of pro-inflammatory cytokines in hypertrophic adipocytes through lipopolysaccharide-stimulated macrophages." Biol Pharm Bull 35(11): 1941-1946.
Kharbanda, R. K., U. M. Mortensen, P. A. White, S. B. Kristiansen, M. R. Schmidt, J. A. Hoschtitzky, M. Vogel, K. Sorensen, A. N. Redington and R. MacAllister (2002). "Transient limb ischemia induces remote ischemic preconditioning in vivo." Circulation 106(23): 2881-2883.
Kim, M. and R. Tian (2011). "Targeting AMPK for cardiac protection: opportunities and challenges." J Mol Cell Cardiol 51(4): 548-553.
Kim, S. Y., J. E. Koo, Y. J. Seo, N. Tyagi, E. Jeong, J. Choi, K. M. Lim, Z. Y. Park and J. Y. Lee (2013). "Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD2." Br J Pharmacol 168(8): 1933-1945.
Knight, R. A., T. M. Scarabelli and A. Stephanou (2012). "STAT transcription in the ischemic heart." Jakstat 1(2): 111-117.
Kumaran, K. S. and P. S. Prince (2010). "Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage." Cell Stress Chaperones 15(6): 791-806.
Kurrelmeyer, K. M., L. H. Michael, G. Baumgarten, G. E. Taffet, J. J. Peschon, N. Sivasubramanian, M. L. Entman and D. L. Mann (2000). "Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction." Proc Natl Acad Sci U S A 97(10): 5456-5461.
Lacerda, L., S. Somers, L. H. Opie and S. Lecour (2009). "Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway." Cardiovasc Res 84(2): 201-208.
Lecour, S., N. Suleman, G. A. Deuchar, S. Somers, L. Lacerda, B. Huisamen and L. H. Opie (2005). "Pharmacological preconditioning with tumor necrosis factor-alpha activates signal transducer and activator of transcription-3 at reperfusion without involving classic prosurvival kinases (Akt and extracellular signal-regulated kinase)." Circulation 112(25): 3911-3918.
Li, P. G., J. W. Xu, K. Ikeda, A. Kobayakawa, Y. Kayano, T. Mitani, T. Ikami and Y. Yamori (2005). "Caffeic acid inhibits vascular smooth muscle cell proliferation induced by angiotensin II in stroke-prone spontaneously hypertensive rats." Hypertens Res 28(4): 369-377.
Lu, Z. and S. Xu (2006). "ERK1/2 MAP kinases in cell survival and apoptosis." IUBMB Life 58(11): 621-631.
Magnani, C., V. L. B. Isaac, M. A. Correa and H. R. N. Salgado (2014). "Caffeic acid: a review of its potential use in medications and cosmetics." Analytical Methods 6(10): 3203-3210.
Marchant, D. J., J. H. Boyd, D. C. Lin, D. J. Granville, F. S. Garmaroudi and B. M. McManus (2012). "Inflammation in myocardial diseases." Circ Res 110(1): 126-144.
Minamino, T. (2012). "Cardioprotection from ischemia/reperfusion injury: basic and translational research." Circ J 76(5): 1074-1082.
Misra, M. K., M. Sarwat, P. Bhakuni, R. Tuteja and N. Tuteja (2009). "Oxidative stress and ischemic myocardial syndromes." Med Sci Monit 15(10): Ra209-219.
Morishima, I., T. Sone, S. Mokuno, S. Taga, A. Shimauchi, Y. Oki, J. Kondo, H. Tsuboi and H. Sassa (1995). "Clinical significance of no-reflow phenomenon observed on angiography after successful treatment of acute myocardial infarction with percutaneous transluminal coronary angioplasty." Am Heart J 130(2): 239-243.
Murry, C. E., R. B. Jennings and K. A. Reimer (1986). "Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium." Circulation 74(5): 1124-1136.
Murtaza, G., S. Karim, M. R. Akram, S. A. Khan, S. Azhar, A. Mumtaz and M. H. H. Bin Asad (2014). "Caffeic Acid Phenethyl Ester and Therapeutic Potentials." BioMed Research International 2014: 9.
Natarajan, K., S. Singh, T. R. Burke, Jr., D. Grunberger and B. B. Aggarwal (1996). "Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B." Proc Natl Acad Sci U S A 93(17): 9090-9095.
Neria, F., M. A. Castilla, R. F. Sanchez, F. R. Gonzalez Pacheco, J. J. Deudero, O. Calabia, A. Tejedor, F. Manzarbeitia, A. Ortiz and C. Caramelo (2009). "Inhibition of JAK2 protects renal endothelial and epithelial cells from oxidative stress and cyclosporin A toxicity." Kidney Int 75(2): 227-234.
Olthof, M. R., P. C. Hollman and M. B. Katan (2001). "Chlorogenic acid and caffeic acid are absorbed in humans." J Nutr 131(1): 66-71.
Oshima, Y., Y. Fujio, T. Nakanishi, N. Itoh, Y. Yamamoto, S. Negoro, K. Tanaka, T. Kishimoto, I. Kawase and J. Azuma (2005). "STAT3 mediates cardioprotection against ischemia/reperfusion injury through metallothionein induction in the heart." Cardiovasc Res 65(2): 428-435.
Paiva-Martins, F. and M. Gordon (2002). "Effects of pH and ferric ions on the antioxidant activity of olive polyphenols in oil-in-water emulsions." Journal of the American Oil Chemists'' Society 79(6): 571-576.
Paiva, M. A., L. M. Goncalves, L. A. Providencia, S. M. Davidson, D. M. Yellon and M. M. Mocanu (2010). "Transitory activation of AMPK at reperfusion protects the ischaemic-reperfused rat myocardium against infarction." Cardiovasc Drugs Ther 24(1): 25-32.
Peart, J. N. and J. P. Headrick (2009). "Clinical cardioprotection and the value of conditioning responses." Am J Physiol Heart Circ Physiol 296(6): H1705-1720.
Rezkalla, S. H. and R. A. Kloner (2002). "No-reflow phenomenon." Circulation 105(5): 656-662.
Sambandam, N. and G. D. Lopaschuk (2003). "AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart." Prog Lipid Res 42(3): 238-256.
Sandberg, E. M. and P. P. Sayeski (2004). "Jak2 tyrosine kinase mediates oxidative stress-induced apoptosis in vascular smooth muscle cells." J Biol Chem 279(33): 34547-34552.
Schulz, R. and G. Heusch (2009). "Tumor necrosis factor-alpha and its receptors 1 and 2: Yin and Yang in myocardial infarction?" Circulation 119(10): 1355-1357.
Sharma, V., R. M. Bell and D. M. Yellon (2012). "Targeting reperfusion injury in acute myocardial infarction: a review of reperfusion injury pharmacotherapy." Expert Opin Pharmacother 13(8): 1153-1175.
Smith, R. M., N. Suleman, L. Lacerda, L. H. Opie, S. Akira, K. R. Chien and M. N. Sack (2004). "Genetic depletion of cardiac myocyte STAT-3 abolishes classical preconditioning." Cardiovasc Res 63(4): 611-616.
Stephanou, A., B. K. Brar, T. M. Scarabelli, A. K. Jonassen, D. M. Yellon, M. S. Marber, R. A. Knight and D. S. Latchman (2000). "Ischemia-induced STAT-1 expression and activation play a critical role in cardiomyocyte apoptosis." J Biol Chem 275(14): 10002-10008.
Sun, B., G. B. Sun, J. Xiao, R. C. Chen, X. Wang, Y. Wu, L. Cao, Z. H. Yang and X. B. Sun (2012). "Isorhamnetin inhibits H(2)O(2)-induced activation of the intrinsic apoptotic pathway in H9c2 cardiomyocytes through scavenging reactive oxygen species and ERK inactivation." J Cell Biochem 113(2): 473-485.
Tan, J., Z. Ma, L. Han, R. Du, L. Zhao, X. Wei, D. Hou, B. H. Johnstone, M. R. Farlow and Y. Du (2005). "Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury." Am J Physiol Heart Circ Physiol 289(5): H2265-2271.
Tolba, M. F., S. S. Azab, A. E. Khalifa, S. Z. Abdel-Rahman and A. B. Abdel-Naim (2013). "Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects." IUBMB Life 65(8): 699-709.
Vinten-Johansen, J., Z. Q. Zhao, R. Jiang, A. J. Zatta and G. P. Dobson (2007). "Preconditioning and postconditioning: innate cardioprotection from ischemia-reperfusion injury." J Appl Physiol (1985) 103(4): 1441-1448.
Weng, Y. C., S. T. Chuang, Y. C. Lin, C. F. Chuang, T. C. Chi, H. L. Chiu, Y. H. Kuo and M. J. Su (2012). "Caffeic Acid Phenylethyl Amide Protects against the Metabolic Consequences in Diabetes Mellitus Induced by Diet and Streptozocin." Evid Based Complement Alternat Med 2012: 984780.
Yellon, D. M. and D. J. Hausenloy (2007). "Myocardial reperfusion injury." N Engl J Med 357(11): 1121-1135.
Yoshiyama, M., K. Takeuchi, A. Hanatani, S. Kim, T. Omura, I. Toda, M. Teragaki, K. Akioka, H. Iwao and J. Yoshikawa (1997). "Differences in expression of sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger genes between adjacent and remote noninfarcted myocardium after myocardial infarction." J Mol Cell Cardiol 29(1): 255-264.
Zhao, Z. Q., J. S. Corvera, M. E. Halkos, F. Kerendi, N. P. Wang, R. A. Guyton and J. Vinten-Johansen (2003). "Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning." Am J Physiol Heart Circ Physiol 285(2): H579-588.
Zmijewski, J. W., S. Banerjee, H. Bae, A. Friggeri, E. R. Lazarowski and E. Abraham (2010). "Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase." J Biol Chem 285(43): 33154-33164.



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