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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
PubMed

Insights

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.

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