Deletion of the Kinase Domain in Death-Associated Protein Kinase Attenuates Tubular Cell Apoptosis in Renal Ischemia-Reperfusion Injury
作者： Masanori Kishino , Kazunori Yukawa , Katsuaki Hoshino , Akihiko Kimura , Nobuyuki Shirasawa
DOI: 10.1097/01.ASN.0000131527.59781.F2
关键词:
摘要: Death-associated protein kinase (DAPK) is a calcium/calmodulin-dependent serine/threonine localized to renal tubular epithelial cells. To elucidate the contribution of DAPK activity apoptosis in ischemia-reperfusion (IR) injury, wild-type (WT) mice and DAPK-mutant mice, which express deletion mutant that lacks portion domain, were subjected pedicle clamping reperfusion. After IR, was elevated WT kidneys but not (1785.7 +/- 54.1 pmol/min/mg versus 160.7 60.6 pmol/min/mg). Furthermore, there more TUNEL-positive nuclei activated caspase 3-positive cells than after IR (24.0 5.9 or 9.4 0.6 per high-power field [HPF] 6.3 2.2 4.4 0.7 cells/HPF at 40 h ischemia). In addition, increase p53-positive tubule greater kidney (9.9 1.4 0.8 0.4 cells/HPF), consistent with theory stabilizes p53 protein. Finally, serum creatinine levels higher (2.54 0.34 mg/dl 0.87 0.24 Thus, these results indicate domain from molecule can attenuate cell dysfunction injury.
jasn.org参考文章(49)
A. Rana, P. Sathyanarayana, W. Lieberthal, Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications. Apoptosis. ,vol. 6, pp. 83- 102 ,(2001) , 10.1023/A:1009680229931
Tal Raveh, Gustavo Droguett, Marshall S. Horwitz, Ronald A. DePinho, Adi Kimchi, DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nature Cell Biology. ,vol. 3, pp. 1- 7 ,(2001) , 10.1038/35050500
Ralph Buttyan, Glenda Gobé, Apoptosis in the Mammalian Kidney: Incidence, Effectors, and Molecular Control in Normal Development and Disease States Advances in pharmacology. ,vol. 41, pp. 369- 381 ,(1997) , 10.1016/S1054-3589(08)61065-0
I. S. Sawczuk, G. Gobé, R. Buttyan, G. J. Wise, K. M. O'Toole, M. Schumer, J. Connor, C. A. Olsson, M. C. Colombel, Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. American Journal of Pathology. ,vol. 140, pp. 831- 838 ,(1992)
Boaz Inbal, Ofer Cohen, Sylvie Polak-Charcon, Juri Kopolovic, Ezra Vadai, Lea Eisenbach, Adi Kimchi, DAP kinase links the control of apoptosis to metastasis Nature. ,vol. 390, pp. 180- 184 ,(1997) , 10.1038/36599
Rachel A. Katzenellenbogen, Stephen B. Baylin, James G. Herman, Hypermethylation of the DAP-Kinase CpG Island Is a Common Alteration in B-Cell Malignancies Blood. ,vol. 93, pp. 4347- 4353 ,(1999) , 10.1182/BLOOD.V93.12.4347.412K31_4347_4353
Boaz Inbal, Shani Bialik, Ilana Sabanay, Gidi Shani, Adi Kimchi, DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death Journal of Cell Biology. ,vol. 157, pp. 455- 468 ,(2002) , 10.1083/JCB.200109094
Prabal K. Chatterjee, Paul A.J. Brown, Salvatore Cuzzocrea, Kai Zacharowski, Keith N. Stewart, Helder Mota-Filipe, Michelle C. Mcdonald, Christoph Thiemermann, Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat. Kidney International. ,vol. 59, pp. 2073- 2083 ,(2001) , 10.1046/J.1523-1755.2001.00722.X
Anastasia V. Velentza, Andrew M. Schumacher, Curtis Weiss, Martin Egli, D. Martin Watterson, A protein kinase associated with apoptosis and tumor suppression: structure, activity, and discovery of peptide substrates. Journal of Biological Chemistry. ,vol. 276, pp. 38956- 38965 ,(2001) , 10.1074/JBC.M104273200
Kazunori Yukawa, Katsuaki Hoshino, Masanori Kishino, Masatoshi Mune, Nobuyuki Shirasawa, Akihiko Kimura, Yuji Tsubota, Kyoko Owada-Makabe, Tetsuji Tanaka, Masakazu Ichinose, Masanobu Maeda, Kiyoshi Takeda, Shizuo Akira, Deletion of the kinase domain in death-associated protein kinase attenuates renal tubular cell apoptosis in chronic obstructive uropathy International Journal of Molecular Medicine. ,vol. 13, pp. 515- 520 ,(2004) , 10.3892/IJMM.13.4.515