Open AccessCaspase‐1 inhibitor Ac‐YVAD‐CHO attenuates quinolinic acid‐induced increases in p53 and apoptosis in rat striatum 1
Author(s) -
CAO Yi,
GU Zhenlun,
LIN Fang,
HAN Rong,
QIN Zhenghong
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00525.x
Subject(s) - apoptosis , quinolinic acid , caspase , caspase 3 , chemistry , caspase 9 , pharmacology , chinese hamster ovary cell , microbiology and biotechnology , programmed cell death , biology , biochemistry , tryptophan , receptor , amino acid
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.