Caspase-1 inhibitor Ac-YVAD-CHO attenuates quinolinic acid-induced increases in p53 and apoptosis in rat striatum
Abstract
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 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 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:
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 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 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.