Skip to main content
Log in

Roles of MAPKAPK-2 and HSP27 in the reduction of renal ischemia–reperfusion injury by ischemic postconditioning in rats

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. 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

    Article  CAS  PubMed  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. 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

    Article  CAS  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  CAS  PubMed  Google Scholar 

  7. 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

    CAS  PubMed  Google Scholar 

  8. 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

    Article  CAS  PubMed  Google Scholar 

  9. Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172

    Article  CAS  PubMed  Google Scholar 

  10. 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

    CAS  PubMed  Google Scholar 

  11. Paller MS, Hoidal JR, Ferris TF (1984) Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74:1156–1164

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. 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

    CAS  PubMed  Google Scholar 

  13. 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

    Article  PubMed  Google Scholar 

  14. 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

    Article  PubMed  Google Scholar 

  15. 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

    Article  CAS  PubMed  Google Scholar 

  16. 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

    Article  CAS  PubMed  Google Scholar 

  17. 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

    Article  CAS  PubMed  Google Scholar 

  18. 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

    CAS  PubMed  Google Scholar 

  19. 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

    PubMed  Google Scholar 

  20. 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

    Article  CAS  PubMed  Google Scholar 

  21. 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

    Article  CAS  PubMed  Google Scholar 

  22. 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

    CAS  PubMed  Google Scholar 

  23. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. 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

    Article  CAS  PubMed  Google Scholar 

  25. Lewis TS, Shapiro PS, Ahn NG (1998) Signal transduction through MAP kinase cascades. Adv Cancer Res 74:49–139

    Article  CAS  PubMed  Google Scholar 

  26. 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

    CAS  PubMed  Google Scholar 

  27. 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

    Article  CAS  PubMed  Google Scholar 

  28. 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

    Article  PubMed  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. 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

    Article  PubMed  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. 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

    Article  CAS  PubMed  Google Scholar 

  34. Concannon CG, Gorman AM, Samali A (2003) On the role of Hsp27 in regulating apoptosis. Apoptosis 8:61–70

    Article  CAS  PubMed  Google Scholar 

  35. Jakob U, Gaestel M, Engel K, Buchner J (1993) Small heat shock proteins are molecular chaperones. J Biol Chem 268:1517–1520

    CAS  PubMed  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Anzhou Xia.

Additional information

Anzhou Xia, Yong Li, Na Li and Zhi Xue have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-014-0748-4

Keywords

Navigation