title: Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment.
abstract: 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.
authors.affiliation: Department of Pharmacology, ZAFES, Biocenter Niederursel, N260 Max-von-Laue Str. 9, University of Frankfurt, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Franke
authors.forename: Michael
authors.initials: M
authors.lastname: Nöldner
authors.forename: Reham
authors.initials: R
authors.lastname: Abdel-Kader
authors.forename: Leslie N
authors.initials: LN
authors.lastname: Johnson-Anuna
authors.forename: W
authors.initials: W
authors.lastname: Gibson Wood
authors.forename: Walter E
authors.initials: WE
authors.lastname: Müller
authors.forename: Gunter P
authors.initials: GP
authors.lastname: Eckert
mesh_terms: 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
chemical_list: 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