Caspase-1 inhibitor Ac-YVAD-CHO attenuates quinolinic acid-induced increases in p53 and apoptosis in rat striatum.
OBJECTIVE
To study the effects of the caspase-1 inhibitor Ac-YVAD-CHO on quinolinic acid (QA)-induced apoptosis.


METHODS
Rats were pre-treated with intrastriatal infusion of Ac-YVAD-CHO (2-8 microg) before intrastriatal injection of QA (60 nmol). Striatal total proteins, genomic DNA, and nuclear proteins were isolated. The effects of Ac-YVAD-CHO on QA-induced caspase-1 activity, internucleosomal DNA fragmentation, IkappaB-alpha degradation, NF-kappaB, and AP-1 activation, and increases in p53 protein levels were measured with enzyme assays, agarose gel electrophoresis, electrophoresis mobility shift assays, and Western blot analysis.


RESULTS
Pre-treatment with Ac-YVAD-CHO inhibited QA-induced internucleosomal DNA fragmentation. Ac-YVAD-CHO inhibited QA-induced increases in caspase-1 activity and p53 protein levels, but had no effect on QA-induced IkappaB-alpha degradation, NF-kappaB or AP-1 activation.


CONCLUSIONS
Caspase-1 is involved in QA-induced p53 upregulation but not IkappaB-alpha degradation. Inhibition of caspase-1 attenuates QA-induced apoptosis in rat striatum.
Cao
Yi
Y
Department of Pharmacology, Soochow University School of Medicine, Suzhou 215007, China.
Gu
Zhen-Lun
ZL
Lin
Fang
F
Han
Rong
R
Qin
Zhen-Hong
ZH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors; D003342:Corpus Striatum / Q000166:cytology* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D061945:Caspase Inhibitors; D009842:Oligopeptides; D016159:Tumor Suppressor Protein p53; C096429:L 709049; D020170:Caspase 1; D017378:Quinolinic Acid