Abstract
Glutamate and the NO donor, nitroprusside, synergistically induced the death of B50 cells from a rat CNS-derived neuroblastoma cell line. With low [nitroprusside] (10 microM) both nitroprusside and glutamate were required. Under these conditions, nuclei became pyknotic and caspases were activated. The activities of caspase-3 and caspase-6 (effector caspases) were higher than those of caspase-8 and caspase-9 (initiator caspases). The activation of all four caspases was inhibited by cyclosporin A, with the order of susceptibility caspase-8=caspase-9=caspase-6>caspase-3. To identify the possible locus of cyclosporin A action, we used an antisense oligodeoxynucleotide to suppress the level of cyclophilin-A to<5% of its control value. Cyclophilin-A suppression largely reproduced the inhibitory effects of cyclosporin A. These results provide the first indication that cyclophilin-A participates in the activation of the caspase cascade in neuronal cells, in particular in the form of cascade elicited by excitotoxic stimuli. It is concluded that neuroprotection by cyclosporin A against excitotoxin-induced apoptosis is, at least partly, due to inhibition of cyclophilin-A.
Citations
Jul 8, 2008·Plant Physiology and Biochemistry : PPB·Eun Kyung Cho, Mihyang Kim
May 14, 2008·Biochemical and Biophysical Research Communications·De-Hua HuoJine Yang
Feb 12, 2008·Progress in Neurobiology·Nils P Hailer
Sep 24, 2010·Alcoholism, Clinical and Experimental Research·Nawal M BoukliMadhavan P N Nair
Sep 25, 2004·Immunology Letters·Hyun Jung KimTae Jin Kim
Jul 14, 2010·The American Journal of Chinese Medicine·Wan-Yu LoChing-Liang Hsieh
Feb 12, 2011·The Journal of International Medical Research·J Lee, S S Kim
Aug 5, 2010·Inflammatory Bowel Diseases·Jeroni LunaMiquel Sans
Mar 22, 2016·Biomarkers in Cancer·Urmila SehrawatGururao Hariprasad
Jan 13, 2006·Proteomics·Monique Dall'AgnolClaire M Payne
May 24, 2007·Journal of Neurotrauma·Amit S KordeWilliam F Maragos
Sep 30, 2004·Journal of Neurotrauma·Stefano SignorettiRoberto Vagnozzi
Feb 12, 2005·World Journal of Surgery·Qizhi YaoChangyi Chen
Oct 17, 2009·The Biochemical Journal·Sylvanie MalouitreMartin Crompton
Jul 20, 2007·The Journal of Experimental Medicine·Changlian ZhuKlas Blomgren
Sep 4, 2008·Infection and Immunity·Dhammika N AtapattuCharles J Czuprynski
Jul 6, 2004·The Biochemical Journal·Yanmin LiMartin Crompton
Jul 31, 2004·Molecular & Cellular Proteomics : MCP·Sheng GuXian Chen
Mar 20, 2003·Molecular & Cellular Proteomics : MCP·Pavel GromovJulio E Celis
Aug 21, 2009·Journal of Medicinal Chemistry·Shuaishuai NiJian Li
Mar 21, 2003·Journal of Proteome Research·Yetrib HathoutCatherine Fenselau
Jan 15, 2013·Journal of Chemical Information and Modeling·Mulpuri NagarajuDonald Hamelberg
Mar 21, 2003·Journal of Medicinal Chemistry·Yong-Qian WuGregory S Hamilton