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

作　　者：YiCAO Zhen-lunGU FangLIN RongHAN Zheng-hongQIN 

机构地区：[1]DepartmentofPharmacology,SoochowUniversitySchoolofMedicine,Suzhou215007,China

出　　处：《Acta Pharmacologica Sinica》2005年第2期150-154,共5页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(№ 30370506).

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(2-8μg)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.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(2-8μg)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.

关 键 词：caspase 1 Ac-YVAD-CHO Huntington disease protein p53 NF-kappaB inhibitor alpha APOPTOSIS NF-KAPPAB 

分 类 号：R971[医药卫生—药品]