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

• 来源期刊: 中国药理学报（英文版）
• 关键词: caspase 1 Ac-YVAD-CHO Huntington disease protein p53 NF-kappaB inhibitor alpha apoptosis NF-kappaB
• 年，卷（期）: 2005,（2）
• 页码范围: 150-154
• 页数: 5页
• 语种: 英文

摘要

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 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.