Apoptosis signaling pathway in a subtotal nephrectomy rat model

Abstract

To investigate the role and mechanisms of apoptosis and apoptosis signaling pathway in 5/6 nephrectomy rat model (SN_X), the mRNA and protein levels of caspase-3,-8,-9 and apoptosis were detected by in situ end labeling (TUNEL), immunohistochemistry, RT-PCR, Western-blotting 1, 2, 4, 8, 12, 16, 26 and 40 weeks after 5/6 nephrectomy rat model was made respectively. The rats in the model group developed glomerular sclerosis and renal interstitial fibrosis. The number of the apoptototic cells in glomeruli, renal tubule and renal interstitium was remarkably higher in the model group than that in the control group (P<0.05, P<0.01). Changes of mRNA and protein level of caspase-3,-8,-9 had the same tendency and was up-regulated wavily in the rat model compared with the control group (P<0.05). Peaks in model appeared on the 4th and the 40th week respectively. The growth amplitude of caspase-9 was remarkably higher than that of caspase-8. It is concluded that the development of 5/6 nephrectomy rat model was correlated with the apoptosis of glomeruli, renal tubule and renal interstitium. Both of death receptor and mitochondria signaling path ways are involved in the process and the latter might play a primary role.

Keywords

5/6 nephrectomy / apoptosis / caspase-3 / caspase-8 / caspase-9

References

[1] SugiyamaH., KashiharaN., MakinoH., et al.. Apoptosis in glomerular sclerosis. Kidney Int, 1996, 49(1): 103-111

[2] PriceP., SafirsteinR., MegyesiJ.. Protection of renal cells from cisplatin toxicity by cell cycle inhibitors. Am J physiol, 2004, 286(2): F378-384

[3] RenatusM., StennickeH. R., ScottF. L., et al.. Dimer formation drives the activation of the cell death protease caspase-9. Proc Natl Acad Sci USA, 2001, 98(25): 14250-14255

[4] AcehanM., JiangX., MorganD.G., et al.. Three-dimensional structure of the apoptosome: implications for assembly,pro-caspase-9 binding, and activation. Mol Cell, 2002, 9(2): 423-432

[5] SuzukiA., TsutomiY., AkahaneK., et al.. Resistance of Fas-mediated apoptosis activation of casepase −3 is regulated by cell cycle regulator by cell cycle regulator p21WAFI and IAP gene family ILP gene family. Oncogene, 1998, 17(4): 931-939

[6] StruzeF., MullerG. A.. The role of tubulointerstitial processes in progression of primary renal diseases. Nephrol Dial Transplant, 1994, 9(suppl): 10-20

[7] SchulerM., BossyE., GoldsteinJ.C., et al.. P53 induces apoptosis by caspase activation through mitochondrial cytochrome C release. J Biol Chem, 2000, 275(17): 7337-7342

[8] RangnathM., StevenE., TimothyK., et al.. High glucose evokes an intrinsic proapoptotic signaling pathway in mesangial cells. Kidney Int, 2005, 67(1): 82-94

[9] BrianS., RickG. S.. Cisplatin-Induced Renal Cell Apoptosis: Caspase 3-Dependent and Independent Pathways. J Pharmacol Exp Ther, 2002, 302(1): 8-17