Activation of caspase-3 in developmental models of programmed cell death in neurons of the substantia nigra.
Programmed cell death has been proposed to play a role in the death of neurons in acute and chronic degenerative neurologic disease. There is now evidence that the caspases, a family of cysteine proteases, mediate programmed cell death in various cells. In neurons, caspase-3 (CPP32/Yama/apopain), in particular, has been proposed to play a role. We examined the expression of caspase-3 in three models of programmed cell death affecting neurons of the substantia nigra in the rat: natural developmental neuron death and induced developmental death following either striatal target injury with quinolinic acid or dopamine terminal lesion with intrastriatal injection of 6-hydroxydopamine. Using an antibody to the large (p17) subunit of activated caspase-3, we have found that activated enzyme is expressed in apoptotic profiles in all models. Increased p17 immunostaining correlated with increased enzyme activity. The subcellular distribution of activated caspase-3 differed among the models: In natural cell death and the target injury model, it was strictly nuclear, whereas in the toxin model, it was also cytoplasmic. We conclude that p17 immunostaining is a useful marker for programmed cell death in neurons of the substantia nigra.
Jeon
B S
BS
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Kholodilov
N G
NG
Oo
T F
TF
Kim
S Y
SY
Tomaselli
K J
KJ
Srinivasan
A
A
Stefanis
L
L
Burke
R E
RE
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation; D015870:Gene Expression; D008954:Models, Biological; D009474:Neurons / Q000201:enzymology*; D016627:Oxidopamine / Q000494:pharmacology; D017378:Quinolinic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
D012333:RNA, Messenger; D016627:Oxidopamine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D017378:Quinolinic Acid; D004298:Dopamine