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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:baronsong2009
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Aim:To study the effects of the caspase-1 inhibitor Ac-YVAD-CHO on quinolinicacid(QA)-induced apoptosis.Methods:Rats were pre-treated with intrastriatalinfusion of Ac-YVAD-CHO(2-8μg)before intrastriatal injection of QA(60 nmol).Striatal total proteins,genomic DNA,and nuclear proteins were isolated.Theeffects of Ac-YVAD-CHO on QA-induced caspase-1 activity,internucleosomalDNA fragmentation, IκB-α degradation,NF-κB,and AP-1 activation,and increasesin 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 incaspase-1 activity and p53 protein levels,but had no effect on QA-induced IκB-αdegradation,NF-κB or AP-1 activation.Conclusion:Caspase-1 is involved inQA-induced p53 upregulation but not IκB-α degradation.Inhibition of caspase-1attenuates 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 intrastriatalinfusion of Ac-YVAD-CHO QA (60 nmol) .Striatal total proteins, genomic DNA, and nuclear proteins were isolated. These 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 activities in p53 protein levels, but had no effect on QA-induced IκB-αdegradation, NF-κB or AP-1 activation. Confluence: Caspase-1 is involved inQA- induced p53 upregulation but not IκB-α degradation. Inhibition of caspase-1 attenuates QA-induced ap optosis in rat striatum.
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