Calpain inhibitor entrapped in liposome rescues ischemic neuronal damage - PubMed (original) (raw)
Calpain inhibitor entrapped in liposome rescues ischemic neuronal damage
M Yokota et al. Brain Res. 1999.
Abstract
Transient forebrain ischemia induces activation of calpain and proteolysis of a neuronal cytoskeleton, fodrin, in gerbil hippocampus. This phenomenon precedes delayed neuronal death in hippocampal CA1 neurons. We examined effects of a calpain inhibitor on delayed neuronal death after transient forebrain ischemia. In gerbils, a selective calpain inhibitor entrapped in liposome was given transvenously and 30 min later, 5-min forebrain ischemia was produced by occlusion of both common carotid arteries. On day 7, CA1 neuronal damage was examined in the hippocampal slices stained with cresyl violet. Calpain-induced proteolysis of fodrin was also examined by immunohistochemistry and immunoblot. Additionally, to assure entrapment of the inhibitor by CA1 neurons, the inhibitor-liposome complex was labeled with FITC and given to gerbils. Fluorescence in the hippocampal slices was examined by confocal laser scanning microscope. Selective CA1 neuronal damage induced by forebrain ischemia was prevented by administration of the inhibitor in a dose-dependent manner. Calpain-induced proteolysis of fodrin was also extinguished by the calpain inhibitor in a dose-dependent manner. Bright fluorescence of the FITC-labeled inhibitor was observed in the CA1 neurons. The data show an important role of calpain in the development of the ischemic delayed neuronal death. Calpain seems to produce neuronal damage by degrading neuronal cytoskeleton. Our data also show a palliative effect of the calpain inhibitor on the neurotoxic damage, which offers a new and potent treatment of transient forebrain cerebral ischemia.
Copyright 1999 Elsevier Science B.V.
Similar articles
- Three distinct phases of fodrin proteolysis induced in postischemic hippocampus. Involvement of calpain and unidentified protease.
Yokota M, Saido TC, Tani E, Kawashima S, Suzuki K. Yokota M, et al. Stroke. 1995 Oct;26(10):1901-7. doi: 10.1161/01.str.26.10.1901. Stroke. 1995. PMID: 7570746 - Calpain induces proteolysis of neuronal cytoskeleton in ischemic gerbil forebrain.
Yokota M, Saido TC, Kamitani H, Tabuchi S, Satokata I, Watanabe T. Yokota M, et al. Brain Res. 2003 Sep 12;984(1-2):122-32. doi: 10.1016/s0006-8993(03)03121-4. Brain Res. 2003. PMID: 12932846 - Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia.
Candelario-Jalil E, Alvarez D, González-Falcón A, García-Cabrera M, Martínez-Sánchez G, Merino N, Giuliani A, León OS. Candelario-Jalil E, et al. Eur J Pharmacol. 2002 Oct 25;453(2-3):189-95. doi: 10.1016/s0014-2999(02)02422-6. Eur J Pharmacol. 2002. PMID: 12398903 - Calpain as a novel target for treating acute neurodegenerative disorders.
Bartus RT, Elliott PJ, Hayward NJ, Dean RL, Harbeson S, Straub JA, Li Z, Powers JC. Bartus RT, et al. Neurol Res. 1995 Aug;17(4):249-58. doi: 10.1080/01616412.1995.11740322. Neurol Res. 1995. PMID: 7477738 Review. - Forebrain ischemia and the blood-cerebrospinal fluid barrier.
Ennis SR, Keep RF. Ennis SR, et al. Acta Neurochir Suppl. 2006;96:276-8. doi: 10.1007/3-211-30714-1_59. Acta Neurochir Suppl. 2006. PMID: 16671470 Review.
Cited by
- Prevention of noise-induced hearing loss by calpain inhibitor MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathway.
Lai R, Fang Q, Wu F, Pan S, Haque K, Sha SH. Lai R, et al. Front Cell Neurosci. 2023 Jul 6;17:1199656. doi: 10.3389/fncel.2023.1199656. eCollection 2023. Front Cell Neurosci. 2023. PMID: 37484825 Free PMC article. - Calpains as mechanistic drivers and therapeutic targets for ocular disease.
Vu JT, Wang E, Wu J, Sun YJ, Velez G, Bassuk AG, Lee SH, Mahajan VB. Vu JT, et al. Trends Mol Med. 2022 Aug;28(8):644-661. doi: 10.1016/j.molmed.2022.05.007. Epub 2022 May 29. Trends Mol Med. 2022. PMID: 35641420 Free PMC article. Review. - New insights into targeting mitochondria in ischemic injury.
Jia J, Jin H, Nan D, Yu W, Huang Y. Jia J, et al. Apoptosis. 2021 Apr;26(3-4):163-183. doi: 10.1007/s10495-021-01661-5. Epub 2021 Mar 9. Apoptosis. 2021. PMID: 33751318 Review. - Neuronal Cell Death.
Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC. Fricker M, et al. Physiol Rev. 2018 Apr 1;98(2):813-880. doi: 10.1152/physrev.00011.2017. Physiol Rev. 2018. PMID: 29488822 Free PMC article. Review. - Calpain research for drug discovery: challenges and potential.
Ono Y, Saido TC, Sorimachi H. Ono Y, et al. Nat Rev Drug Discov. 2016 Dec;15(12):854-876. doi: 10.1038/nrd.2016.212. Epub 2016 Nov 11. Nat Rev Drug Discov. 2016. PMID: 27833121 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous