Expression and differential processing of caspases 6 and 7 in relation to specific epileptiform EEG patterns following limbic seizures.
The caspase family of cell death proteases has been implicated in the mechanism of neuronal death following seizures. We investigated the expression and processing of caspases 6 and 7, putative executioner caspases. Brief limbic seizures were evoked by intraamygdala kainic acid to elicit unilateral death of target hippocampal CA3 neurons in the rat. Seizures rapidly induced cleavage of constitutively expressed caspase-6, followed by elevated VEIDase activity and the proteolysis of lamin A. Neuronal caspase-6 immunoreactivity was markedly upregulated within cortex and hippocampus in relation to bursts of polyspike paroxysmal discharges. In contrast, while caspase-7 expression also increased within cortical and hippocampal neuronal populations in response to the same seizure patterns, caspase-7 was not proteolytically activated. These data highlight differences in expression and activation of caspases 6 and 7 in response to identifiable seizure patterns, focusing potential therapeutic targets for neuroprotection in epilepsy.
Henshall
David C
DC
Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon, USA. dhenshall@Dow.Neurobiology.org
Skradski
Shana L
SL
Meller
Robert
R
Araki
Tomohiro
T
Minami
Manabu
M
Schindler
Clara K
CK
Lan
Jing Quan
JQ
Bonislawski
David P
DP
Simon
Roger P
RP
D000679:Amygdala; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism*; D003292:Convulsants / Q000633:toxicity; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D005910:Glioma / Q000473:pathology; D006367:HeLa Cells / Q000187:drug effects / Q000473:pathology; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D019169:Jurkat Cells / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D034904:Lamin Type A; D034882:Lamins; D008297:Male; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D003292:Convulsants; D004791:Enzyme Inhibitors; D018755:GABA Agonists; D034904:Lamin Type A; D034882:Lamins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C505514:CASP6 protein, human; C505520:CASP7 protein, human; C505518:Casp6 protein, rat; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases; D019311:Staurosporine; D003975:Diazepam; D007608:Kainic Acid