Radiation‑induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z‑VAD‑fmk in the hypoglossal nucleus

  • Authors:
    • Jianguo Li
    • Yan Wang
    • Liqing Du
    • Chang Xu
    • Jia  Cao
    • Qin Wang
    • Qiang Liu
    • Feiyue Fan
  • View Affiliations

  • Published online on: November 20, 2013     https://doi.org/10.3892/etm.2013.1419
  • Pages: 383-388
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Abstract

Numerous studies have demonstrated that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. To investigate the role of caspase, a cell permeable pan-caspase inhibitor, z-VAD-fmk [N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone], was used to investigate the effects of caspase blockade in vivo following irradiation. Adult male Sprague‑Dawley rats (weight, 250‑300 g) underwent irradiation at room temperature with a 4‑Gy dose of radiation. Since z-VAD-fmk does not penetrate the blood‑brain barrier, it was applied intracerebroventricularly via a bolus injection (0.2 µg/h for 1 h). Terminal deoxynucleotidyl transferase dUTP nick end‑labeling (TUNEL) demonstrated that z-VAD‑fmk reduced the numbers of TUNEL-positive cells within the hypoglossal nucleus, suggesting that intervention in the caspase cascade following radiation may have therapeutic applications. The caspase inhibitor z-VAD-fmk reduced the expression and activation of caspase-3, caspase-8 and caspase‑9 in the irradiated rats, indicating that caspase may be a potential therapeutic target in the treatment of brain radiation injury. Treatment with z-VAD-fmk also reduced the appearance of cytochrome c within the cytosolic fraction following radiation. The hypoglossal nucleus may be used as a model of radiation‑induced injury in the central nervous system, providing visual information and displaying apoptotic nuclear morphology.
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2014-February
Volume 7 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Li J, Wang Y, Du L, Xu C, Cao J, Wang Q, Liu Q and Fan F: Radiation‑induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z‑VAD‑fmk in the hypoglossal nucleus. Exp Ther Med 7: 383-388, 2014.
APA
Li, J., Wang, Y., Du, L., Xu, C., Cao, J., Wang, Q. ... Fan, F. (2014). Radiation‑induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z‑VAD‑fmk in the hypoglossal nucleus. Experimental and Therapeutic Medicine, 7, 383-388. https://doi.org/10.3892/etm.2013.1419
MLA
Li, J., Wang, Y., Du, L., Xu, C., Cao, J., Wang, Q., Liu, Q., Fan, F."Radiation‑induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z‑VAD‑fmk in the hypoglossal nucleus". Experimental and Therapeutic Medicine 7.2 (2014): 383-388.
Chicago
Li, J., Wang, Y., Du, L., Xu, C., Cao, J., Wang, Q., Liu, Q., Fan, F."Radiation‑induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z‑VAD‑fmk in the hypoglossal nucleus". Experimental and Therapeutic Medicine 7, no. 2 (2014): 383-388. https://doi.org/10.3892/etm.2013.1419