Caspase-9 Takes Part in Programmed Cell Death in Developing Mouse Kidney

Abstract

Programmed cell death is a mechanism by which organisms dispose of unwanted cells, and it is thought to be an important process in organogenesis. We have already reported the role of caspase-3 in the developing metanephros. While caspase-3 is thought to be positioned downstream of the caspase-activating cascade, the upstream caspase for programmed cell death in the developing kidney is still unknown. In an attempt to identify it, we blocked caspase activity in metanephric explants with caspase inhibitors. Administration of a caspase-9 inhibitor (Ac-IETD-CHO) effectively prevented both ureteric bud branching and nephrogenesis, the same as a caspase-3 inhibitor (Ac-DEVD-CHO). On the other hand, administration of a caspase-8 inhibitor (Ac-LETD-CHO) did not inhibit ureteric bud branching or nephrogenesis. Apaf-1, which executes programmed cell death in the caspase-9-related pathway, was detected in the cells exhibiting caspase-9 activity, and our results suggest that Apaaf-1/caspase-9 activates caspase-3 in kidney organogenesis.

Journal

Journal ID (publisher-id): NEE

Journal ID (nlm-ta): Nephron Exp Nephrol

Journal ID (doi): 10.1159/issn.1660-2129

Title: Cardiorenal Medicine

Publisher: S. Karger AG

ISSN (Electronic): 1660-2129

Publication date Subscription-year: 2003

Publication date (Print): March 2003

Publication date (Electronic): 17 November 2004

Volume: 93

Issue: 3

Pages: e117-e124

Affiliations

^aDepartment of Internal Medicine, Keio University School of Medicine, Tokyo; ^bBioarchitect Research Group, Cellular and Molecular Biology Laboratory, RIKEN (Institute of Physical and Chemical Research), Saitama, Japan

Article

Publisher ID: 69552 Other ID: Nephron Exp Nephrol 2003;93:e117–e124

DOI: 10.1159/000069552

PubMed ID: 12660414

Copyright statement: © 2003 S. Karger AG, Basel

License:

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Page count

Figures: 7, References: 40, Pages: 1

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Categories

Subject: Original Paper