Journal article

Publication year: 2007

Pages: 77-86

Journal: Journal of Neurochemistry

Volume number: 101

Issue number: 1

ISSN: 0022-3042

DOI Link: https://doi.org/10.1111/j.1471-4159.2006.04375.x

Publisher: Wiley

Abstract: 
Statins are most commonly prescribed to reduce hypercholesterolemia; however, recent studies have shown that statins have additional benefits, including neuroprotection. Until now, the mechanism underlying statin-induced neuroprotection has been poorly understood. Recent in vivo studies from our lab reported the novel finding that simvastatin increased expression levels of a gene encoding for a major cell survival protein, bcl-2 [Johnson-Anuna et al., J. Pharmacol. Exp. Ther.312 (2005) 786]. The purpose of the present experiments was to determine if simvastatin could protect neurons from excitotoxicity by altering Bcl-2 levels. Neurons were pre-treated with simvastatin and challenged with a compound known to reduce Bcl-2 levels and induce cell death. Simvastatin pre-treatment resulted in a significant reduction in cytotoxicity (lactate dehydrogenase release and caspase 3 activation) following challenge compared with unchallenged neurons. In addition, chronic simvastatin treatment significantly increased Bcl-2 mRNA and protein levels while challenge resulted in a significant reduction in Bcl-2 protein abundance. G3139, an antisense oligonucleotide directed against Bcl-2, abolished the protective effects of simvastatin and eliminated simvastatin-induced up-regulation of Bcl-2 protein. These findings suggest that neuroprotection by simvastatin is dependent on the drug's previously unexplored and important effect of up-regulating Bcl-2.

Harvard Citation style: Johnson-Anuna, L., Eckert, G., Franke, C., Igbavboa, U., Müller, W. and Wood, W. (2007) Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein, Journal of Neurochemistry, 101(1), pp. 77-86. https://doi.org/10.1111/j.1471-4159.2006.04375.x

APA Citation style: Johnson-Anuna, L., Eckert, G., Franke, C., Igbavboa, U., Müller, W., & Wood, W. (2007). Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. Journal of Neurochemistry. 101(1), 77-86. https://doi.org/10.1111/j.1471-4159.2006.04375.x