Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro.
Members of the CED-3/interleukin-1 beta-converting enzyme (ICE) protease family have been implicated in cell death in both invertebrates and vertebrates. In this report, we show that peptide inhibitors of ICE arrest the programmed cell death of motoneurons in vitro as a result of trophic factor deprivation and in vivo during the period of naturally occurring cell death. In addition, interdigital cells that die during development are also rescued in animals treated with ICE inhibitors. Taken together, these results provide the first evidence that ICE or an ICE-like protease plays a regulatory role not only in vertebrate motoneuron death but also in the developmentally regulated deaths of other cells in vivo.
Milligan
C E
CE
Department of Biology, University of Massachusetts, Amherst 01003, USA.
Prevette
D
D
Yaginuma
H
H
Homma
S
S
Cardwell
C
C
Fritz
L C
LC
Tomaselli
K J
KJ
Oppenheim
R W
RW
Schwartz
L M
LM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D002478:Cells, Cultured; D002642:Chick Embryo; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000737:chemistry; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D014020:Tissue Extracts / Q000494:pharmacology; D014034:Toes / Q000196:embryology
D015853:Cysteine Proteinase Inhibitors; D014020:Tissue Extracts; D003546:Cysteine Endopeptidases; D020170:Caspase 1