Abstract
Purpose
Ischemic postconditioning is a procedure during which intermittent reperfusions are performed in the early phase of reperfusion to protect organs from ischemia/reperfusion injury. And in this study, we mainly investigated the injury-alleviative role of mitogen-activated protein kinase-activating protein kinase-2 (MAPKAPK-2) and heat shock protein 27 (HSP27) in renal ischemic reperfusion injury during the procedure of ischemic postconditioning.
Methods
Sprague-Dawley rats were randomly divided into four groups. The injury models were prepared by clipping the left renal pedicle of rats after ligating the right renal pedicle for 60 min. In the ischemic postconditioning group, sequential reperfusions were done for 10 s and another ischemia for 10 s for six cycles after kidney ischemia for 60 min. In addition, the specific inhibitor SB203580 was injected through caudal vein before ischemia. Serum creatinine, blood urea nitrogen and the expression of HSP27 and MAPKAPK-2 were detected 1, 3, 6 and 24 h later after reperfusion. Furthermore, phosphorylation of HSP27 and MAPKAPK-2 protein contents, histological changes and apoptosis were compared 24 h later after reperfusion.
Results
Our data showed that ischemic postconditioning attenuated the renal dysfunction and cell apoptosis induced by I/R and increased phosphorylation of MAPKAPK-2 and HSP27. The results indicated that ischemic postconditioning decreased apoptosis and improved renal function.
Conclusions
Taken together, it is suggested that the renal protective effect may be related to the levels of HSP27 and MAPKAPK-2 activation.
Similar content being viewed by others
References
Kin H, Zatta AJ, Lofye MT, Amerson BS, Halkos ME, Kerendi F, Zhao ZQ, Guyton RA, Headrick JP, Vinten-Johansen J (2005) Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine. Cardiovasc Res 67:124–133
Bopassa JC, Ferrera R, Gateau-Roesch O, Couture-Lepetit E, Ovize M (2006) PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning. Cardiovasc Res 69:178–185
Sun HY, Wang NP, Halkos M, Kerendi F, Kin H, Guyton RA, Vinten-Johansen J, Zhao ZQ (2006) Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. Apoptosis 11:1583–1593
Liu X, Chen H, Zhan B, Xing B, Zhou J, Zhu H, Chen Z (2007) Attenuation of reperfusion injury by renal ischemic postconditioning: the role of NO. Biochem Biophys Res Commun 359:628–634
Steenbergen C (2002) The role of p38 mitogen-activated protein kinase in myocardial ischemia/reperfusion injury; relationship to ischemic preconditioning. Basic Res Cardiol 97:276–285
Ping P, Murphy E (2000) Role of p38 mitogen-activated protein kinases in preconditioning: a detrimental factor or a protective kinase? Circ Res 86:921–922
Guay J, Lambert H, Gingras-Breton G, Lavoie JN, Huot J, Landry J (1997) Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27. J Cell Sci 110:357–368
Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J, Gaestel M (1999) Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J Biol Chem 274:18947–18956
Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172
Huot J, Houle F, Spitz DR, Landry J (1996) HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res 56:273–279
Paller MS, Hoidal JR, Ferris TF (1984) Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74:1156–1164
Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588
Lønborg J, Kelbaek H, Vejlstrup N, Jørgensen E, Helqvist S, Saunamäki K, Clemmensen P, Holmvang L, Treiman M, Jensen JS, Engstrøm T (2010) Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance. Circ Cardiovasc Interv 3:34–41
Liu KX, Li YS, Huang WQ, Chen SQ, Wang ZX, Liu JX, Xia Z (2009) Immediate postconditioning during reperfusion attenuates intestinal injury. Intensive Care Med 35:933–942
Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J (2004) Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62:74–85
Sun HY, Wang NP, Kerendi F, Halkos M, Kin H, Guyton RA, Vinten-Johansen J, Zhao ZQ (2005) Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol 288:H1900–H1908
Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J, Przyklenk K (2005) Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol 289:H1618–H1626
Zhao H, Sapolsky RM, Steinberg GK (2006) Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats. J Cereb Blood Flow Metab 26:1114–1121
Sun K, Liu ZS, Sun Q (2004) Role of mitochondria in cell apoptosis during hepatic ischemia–reperfusion injury and protective effect of ischemic postconditioning. World J Gastroenterol 10:1934–1938
Chen H, Xing B, Liu X, Zhan B, Zhou J, Zhu H, Chen Z (2008) Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat. Transpl Int 21:364–371
Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH (1996) Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res 79:162–173
Maulik N, Yoshida T, Zu YL, Sato M, Banerjee A, Das DK (1998) Ischemic preconditioning triggers tyrosine kinase signaling: a potential role for MAPKAP kinase 2. Am J Physiol 275:H1857–H1864
Liao P, Wang SQ, Wang S, Zheng M, Zheng M, Zhang SJ, Cheng H, Wang Y, Xiao RP (2002) p38 Mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes. Circ Res 90:190–196
Wang M, Sankula R, Tsai BM, Meldrum KK, Turrentine M, March KL, Brown JW, Dinarello CA, Meldrum DR (2004) P38 MAPK mediates myocardial proinflammatory cytokine production and endotoxin-induced contractile suppression. Shock 21:170–174
Lewis TS, Shapiro PS, Ahn NG (1998) Signal transduction through MAP kinase cascades. Adv Cancer Res 74:49–139
Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180
Sun XC, Li WB, Li QJ, Zhang M, Xian XH, Qi J, Jin RL, Li SQ (2006) Limb ischemic preconditioning induces brain ischemic tolerance via p38 MAPK. Brain Res 1084:165–174
Claytor RB, Aranson NJ, Ignotz RA, Lalikos JF, Dunn RM (2007) Remote ischemic preconditioning modulates p38 MAP kinase in rat adipocutaneous flaps. J Reconstr Microsurg 23:93–98
Heidbreder M, Naumann A, Tempel K, Dominiak P, Dendorfer A (2008) Remote vs. ischaemic preconditioning: the differential role of mitogen-activated protein kinase pathways. Cardiovasc Res 78:108–115
Dérijard B, Raingeaud J, Barrett T, Wu IH, Han J, Ulevitch RJ, Davis RJ (1995) Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267:682–685
Stein B, Brady H, Yang MX, Young DB, Barbosa MS (1996) Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade. J Biol Chem 271:11427–11433
Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D, Hunt T, Nebreda AR (1994) A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78:1027–1037
Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (1995) Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270:7420–7426
Concannon CG, Gorman AM, Samali A (2003) On the role of Hsp27 in regulating apoptosis. Apoptosis 8:61–70
Jakob U, Gaestel M, Engel K, Buchner J (1993) Small heat shock proteins are molecular chaperones. J Biol Chem 268:1517–1520
Acknowledgments
This study was supported by a grant from the Bureau of Science and Technology, Xuzhou, China (XF10C072). We declare that no conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication.
Author information
Authors and Affiliations
Corresponding author
Additional information
Anzhou Xia, Yong Li, Na Li and Zhi Xue have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Xia, A., Li, Y., Li, N. et al. Roles of MAPKAPK-2 and HSP27 in the reduction of renal ischemia–reperfusion injury by ischemic postconditioning in rats. Int Urol Nephrol 46, 1455–1464 (2014). https://doi.org/10.1007/s11255-014-0748-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-014-0748-4