Acta Pharmacologica Sinica 2005 February; 26 (2): 150-154; doi: 10.1111/j.1745-7254.2005.00525.x

Aim: 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 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 electro-phoresis, electrophoresis mobility shift assays, and Western blot analysis.

Results: Pre-treatment with Ac-YVAD-CHO inhibited QA-induced internucleo-somal 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.

Conclusion: 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.

Keywords: caspase 1; Ac-YVAD-CHO; Huntington disease; protein p53; NF-kappaB inhibitor alpha; apoptosis; NF-kappaB