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Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve.

Authors: Li, Jianguo  Lin, Li  Du, Liqing  Xu, Chang  Wang, Yan  Cao, Jia  Wang, Qin  Fan, Feiyue  Wang, Xiaoping  Wang, Yafei  Liu, Qiang 
Citation: Li J, etal., Mol Med Rep. 2014 Sep;10(3):1433-7. doi: 10.3892/mmr.2014.2334. Epub 2014 Jun 16.
Pubmed: (View Article at PubMed) PMID:24939579
DOI: Full-text: DOI:10.3892/mmr.2014.2334

There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. Caspases are the key regulators of apoptosis. Healthy male Sprague-Dawley rats were used in the present study to examine the radioprotective effect of a type of pan-caspase inhibitor, z-VAD-fmk, following radiation, to investigate the effects of caspase blockade in a model of the nucleus of the abducens nerve. z-VAD-fmk was injected intracerebroventricularly as a bolus injection (0.2 µg/h for 1 h) into rats prior to exposure to radiation. Irradiation was conducted at room temperature at a dose of radiation of 4 Gy. The present study performed immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot analysis and identified no significant changes in the expression of the X-linked inhibitor of apoptosis protein (XIAP) following radiation (P>0.05). As compared with the radiation alone group, the quantification of TUNEL-positive neurons was reduced in z-VAD-fmk-treated animals following radiation (P<0.01). Inhibition of caspase induced by z-VAD-fmk reduced the expression and activation of caspase-3, -8 and -9 (P<0.01). z-VAD-fmk effectively prevented radiation-induced apoptosis and this caspase inhibitor may be a potential therapeutic target in the treatment of brain radiation injury. The nucleus of the abducens nerve may be used as a radiation injury model, providing visual information and data on the apoptotic morphology of the abducens nucleus.


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RGD Object Information
RGD ID: 13782350
Created: 2018-09-06
Species: All species
Last Modified: 2018-09-06
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.