To study the effects of the caspase-1 inhibitor Ac-YVAD-CHO on quinolinic acid (QA)-induced apoptosis.
Rats were pre-treated with intrastriatal infusion of Ac-YVAD-CHO (2-8 μg) 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, IκB-α degradation, NF-κB, 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.
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 IκB-α degradation, NF-κB or AP-1 activation.
Caspase-1 is involved in QA-induced p53 upregulation but not IκB-α degradation. Inhibition of caspase-1 attenuates QA-induced apoptosis in rat striatum.
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Project supported by the National Natural Science Foundation of China (No 30370506).
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