Caspase-9 takes part in programmed cell death in developing mouse kidney.
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.
Araki
Takashi
T
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hayashi
Matsuhiko
M
Nakanishi
Keiko
K
Morishima
Nobuhiro
N
Saruta
Takao
T
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000196:embryology* / Q000502:physiology; D007684:Kidney Tubules / Q000737:chemistry / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology / Q000502:physiology*; D014513:Ureter / Q000737:chemistry / Q000187:drug effects / Q000196:embryology / Q000502:physiology
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D011506:Proteins; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases