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Acta Pharmacologica Sinica 2005 February; 26 (2): 150-154; doi: 10.1111/j.1745-7254.2005.00525.x |
| Original Article | [
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| Caspase-1 inhibitor Ac-YVAD-CHO attenuates quinolinic acid-induced increases in p53 and apoptosis in rat striatum1 |
| Yi CAO, Zhen-lun GU, Fang LIN, Rong HAN, Zheng-hong QIN2 Department of Pharmacology, Soochow University School of Medicine, Suzhou 215007, China |
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 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. |
Keywords: caspase 1; Ac-YVAD-CHO; Huntington disease; protein p53; NF-kappaB inhibitor alpha; apoptosis; NF-kappaB |
| 1 Project supported by the National Natural Science
Foundation of China (No 30370506). 2 Correspondence to Zheng-hong QIN, PhD. Phn 86-512-6512-2087. Fax 86-512-6519-0599. Email zhqin5@hotmail.com Received 2004-07-21 Accepted 2004-10-25 |
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