Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment.
The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.
Franke
Cornelia
C
Department of Pharmacology, ZAFES, Biocenter Niederursel, N260 Max-von-Laue Str. 9, University of Frankfurt, Germany.
Nöldner
Michael
M
Abdel-Kader
Reham
R
Johnson-Anuna
Leslie N
LN
Gibson Wood
W
W
Müller
Walter E
WE
Eckert
Gunter P
GP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000819:agonists / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D019821:Simvastatin; D020169:Caspases