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Caspase-9 takes part in programmed cell death in developing mouse kidney
Takashi Araki1, Matsuhiko Hayashi, Keiko Nakanishi
1Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nephron. Experimental Nephrology
|March 28, 2003
Summary
This study identifies caspase-9 as the upstream caspase initiating programmed cell death during kidney development. Caspase-9 activation leads to caspase-3 activation, crucial for ureteric bud branching and nephrogenesis.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Programmed cell death is essential for organogenesis.
- Caspase-3's role in metanephros development is known, but upstream caspases remain unidentified.
- Identifying upstream caspases is key to understanding kidney development.
Purpose of the Study:
- To identify the upstream caspase responsible for programmed cell death in the developing kidney.
- To elucidate the caspase-activating cascade in metanephric organogenesis.
Main Methods:
- Metanephric explants were treated with specific caspase inhibitors (caspase-9, caspase-8, and caspase-3 inhibitors).
- Ureteric bud branching and nephrogenesis were assessed following inhibitor administration.
- Apaf-1 expression and caspase-9 activity were analyzed in developing kidney cells.
Main Results:
- Caspase-9 inhibition (Ac-IETD-CHO) blocked ureteric bud branching and nephrogenesis, similar to caspase-3 inhibition (Ac-DEVD-CHO).
- Caspase-8 inhibition (Ac-LETD-CHO) had no significant effect on kidney development.
- Apaf-1 was detected in cells with caspase-9 activity, supporting its role in the pathway.
Conclusions:
- Caspase-9, not caspase-8, acts upstream of caspase-3 in the programmed cell death pathway during kidney organogenesis.
- The Apaf-1/caspase-9 complex likely activates caspase-3, regulating ureteric bud branching and nephrogenesis.
- This finding clarifies a critical step in the molecular regulation of kidney development.