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

被引：18

作者：

Cao, Y ^{[1
]}

Gu, ZL ^{[1
]}

Lin, F ^{[1
]}

Han, R ^{[1
]}

Qin, ZH ^{[1
]}

机构：

[1] Soochow Univ, Sch Med, Dept Pharmacol, Suzhou 215007, Peoples R China

来源：

ACTA PHARMACOLOGICA SINICA | 2005年 / 26卷 / 02期

关键词：

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

D O I：

10.1111/j.1745-7254.2005.00525.x

中图分类号：

O6 [化学];

学科分类号：

0703 ;

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 mug) 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 IKB-alpha degradation, NF-kappaB or AP-1 activation. Conclusion: Caspase-1 is involved in QA-induced p53 upregulation but not IKB-alpha degradation. Inhibition of caspase-1 attenuates QA-induced apoptosis in rat striatum.

引用

页码：150 / 154

页数：5

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