Deletion of the kinase domain in death-associated protein kinase attenuates renal tubular cell apoptosis in chronic obstructive uropathy.

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

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-dependent serine/threonine kinase that has been implicated as a positive mediator of apoptosis. However, little is known about the involvement of DAPK in the apoptosis associated with several pathological states, except for cancer. Here, DAPK-mutant mice were used in order to examine the role of DAPK in renal cell apoptosis in chronic obstructive uropathy (COU) created by unilateral ureteral ligation. These mice express mutant DAPK with a deletion of 74 amino acids from the catalytic kinase domain. Obstructed kidneys in wild-type and mutant mice were examined for both DAPK protein levels and renal cell apoptosis during the course of COU. Obstructed kidneys in wild-type and mutant mice showed a marked increase in the DAPK and mutant DAPK protein levels, respectively, at day 14 after ureteric ligation. The obstructed kidneys in DAPK-mutant mice displayed a significant attenuation of tubular cell apoptosis, compared with wild-type mice. In contrast, no significant difference in interstitial cell apoptosis was observed between the obstructed kidneys from wild-type and mutant mice. Thus, these results indicate that the part of the kinase domain deleted by the gene targeting is crucial for the execution of tubular cell apoptosis, but is not essential for interstitial cell apoptosis in a COU model in mice.

Original languageEnglish
Pages (from-to)515-520
Number of pages6
JournalInternational journal of molecular medicine
Volume13
Issue number4
Publication statusPublished - 2004 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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