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01-03-2011

Protective Effect of FK506 on Myocardial Ischemia/Reperfusion Injury by Suppression of CaN and ASK1 Signaling Circuitry

Authors: Xing Feng, Jing Li, Jinyu Liu, Minghua Jin, Xiaomei Liu, Haiying Du, Long Zhang, Zhiwei Sun, Xiaoguang Li

Published in: Cardiovascular Toxicology | Issue 1/2011

Abstract

We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.

Derek, M. Y., & Derek, J. H. (2007). Myocardial reperfusion injury. The New England Journal of Medicine, 357, 1121–1135.CrossRef

Bishopric, N. H., Andreka, P., Slepak, T., & Webster, K. A. (2001). Molecular mechanisms of apoptosis in the cardiac myocyte. Current Opinion in Pharmacology, 2, 141–150.CrossRef

Uchiyama, T., Otani, H., Okada, T., Ninomiya, H., Kido, M., Imamura, H., et al. (2002). Nitric oxide induces caspase-dependent apoptosis and necrosis in neonatal rat cardiomyocytes. Journal of Molecular and Cellular Cardiology, 8, 1049–1061.CrossRef

Aoki, H., Kang, P. M., Hampe, J., Yoshimura, K., Noma, T., Matsuzaki, M., et al. (2002). Direct activation of mitochondrial apoptosis machinery by c-Jun N-teminal kinase in adult cardiac myocytes. The Journal of Biological Chemistry, 12, 10244–10250.CrossRef

Bueno, O. F., & Molekentin, J. D. (2002). Involvement of extracellular signal-regulated kinases 1/2 in caediac hypertrophy and cell death. Circulation Research, 9, 776–781.CrossRef

Aqqeli, I. K., Beis, I., & Gaitanaki, C. (2008). Oxidantive stress and calpain inhibition induce alphaB—crystallin phosphorylation via p38-MAPK and calcium signalling pathways in H9c2 cells. Cellular Signalling, 7, 1292–1302.

Matsui, T., Li, L., Wu, J. C., Cook, S. A., Naqoshi, T., Picard, M. H., et al. (2002). Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. The Journal of Biological Chemistry, 277, 22896–22901.CrossRefPubMed

Brar, B. K., Stephanou, A., Pennica, D., & Latchman, D. S. (2001). CT-I mediated cardioprotection against ischemic re-oxygenation injury is mediated by PI3 kinase, Akt and MEK1/2 pathways. Cytokine, 3, 93–96.CrossRef

Liu, J., Mao, W., Ding, B., & Liang, C. S. (2008). ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cadiomyocytes. American Journal of Physiology. Heart and Circulatory Physiology, 5, 1956–1965.CrossRef

10.

Prasad, A. M., & Inesi, G. (2009). Effects of thapsigargin and phenylephrine on calcineurin and protein kinase C signaling functions in cardiac myocytes. The American Journal of Physiology, 5, 992–1002.CrossRef

11.

Kakita, T., Hasegawa, K., Iwai-Kanai, E., Adachi, S., Morimoto, T., Wada, H., et al. (2001). Calcineurin pathway is required for endothelin-1- mediated protection against oxidant stress-induced apoptosis in cardiac myocyted. Circulation Research, 12, 1239–1246.CrossRef

12.

De, W. L. J., Lim, H. W., Taigen, T., Wencker, D., Condorelli, G., Dorn, G. W., II, et al. (2000). Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: An apoptosis-independent model of dilated heart failure. Circulation Research, 3, 255–263.

13.

Saito, S., Hiroi, Y., Zou, Y., Aikawa, R., Toko, H., Shibasaki, F., et al. (2000). Beta-Adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes. The Journal of Biological Chemistry, 44, 34528–34533.CrossRef

14.

Shibasaki, F., Hallin, U., & Uchino, H. (2002). Calcineurin as a multifunction regulator. Journal of Biochemistry, 1, 1–15.

15.

Hayashida, K., Sano, M., Ohsawa, I., Ahinmura, K., Tamaki, K., Kimura, K., et al. (2008). Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochemical and Biophysical Research Communications, 1, 30–35.CrossRef

16.

Wang, P., Cao, X., Nagel, D. J., & Yin, G. (2007). Activation of ASK1 during reperfusion of ischemic spinal cord. Neuroscience Letters, 3, 248–252.CrossRef

17.

Takeda, K., Matsuzawa, A., Nishitoh, H., & Ichijo, H. (2003). Roles of MAPKKK ASK1 in stress-induced cell death. Cell Structure and Function, 1, 23–29.CrossRef

18.

Takeda, K., Matsuzawa, A., Nishitoh, H., Tobiume, K., Kishida, S., Ninomiya-Tsuji, J., et al. (2004). Involvement of ASK1 in Ca²⁺-induced p38 MAP kinase activation. EMBO Reports, 2, 161–166.CrossRef

19.

EI-Batawy, M. M., Bosseila, M. A., Mashaly, H. M., & Hafez, V. S. (2009). Topical calcineurin inhibitors in atopic dermatitis: A systematic review and meta-analysis. Journal of Dermatological Science, 5, 76–87.CrossRef

20.

Taylor, A. L., Watson, C. J., & Bradley, J. A. (2005). Immunosuppressive agents in solid organ transplantation: Machanisms of action and therapeutic efficacy. Critical Reviews in Oncology/hematology, 10, 23–46.

21.

Sugiura, R., Sio, S. O., Shuntoh, H., & Kuno, T. (2001). Molecular genetic analysis of the calcineurin signalling pathways. Cellular and Molecular Life Sciences, 2, 278–288.CrossRef

22.

Abou-Jaoude, M. M., Ghantous, I., & Almawi, W. Y. (2003). Tacrolimus (FK506) versus cyclosporin a microemulsion (Neoral) maintenance immunosuppression: Effects on graft survival and function, infection, and metabolic profile following kidney transplantation (KT). Molecular Immunology, 39, 1095–1100.CrossRefPubMed

23.

Michael, L. H., Entman, M. L., Hartley, C. J., Youker, K. A., Zhu, J., Hall, S. R., et al. (1995). Myocardial ischemia and reperfusion: A murine model. The American Journal of Physiology, 2, 2147–2154.

24.

Barnes, C. S., & Coker, S. J. (1995). Failure of nitric oxide donors to alter arrhythmias induced by acute myocardial ischemia of reperfusion in anaesthetized rats. British Journal of Pharmacology, 2, 349–536.

25.

Pallen, C. J., & Wang, J. H. (1983). Calmodulin-stimulated dephosphorylation of P- nitrophenyl phosphate and free phoaphotyrosine by valcineurin. The Journal of Biological Chemistry, 14, 8550–8553.

26.

Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248–254.CrossRefPubMed

27.

Cardenas, M. E., Muir, R. S., Breuder, T., & Heitman, J. (1995). Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A. The EMBO Journal, 12, 2772–2783.

28.

Klee, C. B., Ren, H., & Wang, X. (1998). Regulation of the calmodulin-stimulated protein phosphatade, calcineurin. The Journal of Biological Chemistry, 22, 133367–133370.

29.

Faulds, D., Goa, K. L., & Benfield, P. (1993). Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs, 45, 953–1040.CrossRefPubMed

30.

Schreiber, S. L., & Crabtree, G. R. (1992). The mechanism of action of cyclosporin A and FK506. Immunology Today, 13, 136–142.CrossRefPubMed

31.

Serkova, N. J., Christians, U., & Benet, L. Z. (2004). Biochemical mechanisms of cyclosporine neurotoxicity. Molecular Interventions, 4, 97–107.CrossRefPubMed

32.

Lioberas, N., Torras, J., Alperovich, G., & Cruzado, J. M. (2008). Different renal toxicity profiles in association of cyclosporine and tacrolimus with sirolimus in rats. Nephrology, Dialysis, Transplantation, 10, 3111–3119.CrossRef

33.

Martinez-Martinez, S., & Redondo, J. M. (2004). Inhibitors of the calcineurin/NFAT pathway. Currents Medicinal Chemistry, 8, 997–1007.CrossRef

34.

Kaminuma, O. (2008). Selective inhibitors of nuclear factor of activated T cells: Potential therapeutic drugs for the treatment of immunological and inflammatory diseases. Inflammation and Allergy Drug Targets, 7, 35–40.CrossRefPubMed

35.

Zecchin, K. G., Seidinger, A. L., Chiaratti, M. R., Degasperi, G. R., Meirelles, F. V., Castilho, R. F., et al. (2007). High Bcl-2/Bax ratio in Walker tumor cells protects mitochondria but does not provent H2O2-induced apoptosis via calcineurin pathways. Journal of Bioenergetics and Biomembranes, 2, 186–194.CrossRef

36.

Shibasaki, F., Kondo, E., Akaqi, T., & Mckeon, F. (1997). Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2. Nature, 6626, 728–731.CrossRef

37.

Nomura, M., Shimizu, S., Suqiyama, T., Narita, M., Ito, T., Matsuda, H., et al. (2003). 14-3-3 interacts directly with and negatively regulates pro-apoptotic Bax. The Journal of Biological Chemistry, 3, 2058–2065.CrossRef

38.

Fill, M., Zahrad, A., Villalba, C. A., Zahradnik, I., Escobar, A. L., & Gyorke, S. (2000). Ryanodine receptor adaptation. The Journal of General Physiology, 6, 873–882.CrossRef

39.

Liu, Q., Wilkins, B. J., Lee, Y. J., Ichijo, H., & Molkentin, J. D. (2006). Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT control cardiomyocyte death and growth. Molecular Cell Biology, 10, 3785–3797.CrossRef

40.

Goldman, E. H., Chen, L., & Fu, H. (2004). Activation of apoptosis signal-regulation kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. The Journal of Biological Chemistry, 11, 10442–11049.

Title: Protective Effect of FK506 on Myocardial Ischemia/Reperfusion Injury by Suppression of CaN and ASK1 Signaling Circuitry
Authors: Xing Feng
Jing Li
Jinyu Liu
Minghua Jin
Xiaomei Liu
Haiying Du
Long Zhang
Zhiwei Sun
Xiaoguang Li
Publication date: 01-03-2011
Publisher: Humana Press Inc
Published in: Cardiovascular Toxicology / Issue 1/2011
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-010-9095-6

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Protective Effect of FK506 on Myocardial Ischemia/Reperfusion Injury by Suppression of CaN and ASK1 Signaling Circuitry

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