Simvastatin promotes heat shock protein 27 expression and Akt activation in the rat retina and protects axotomized retinal ganglion cells in vivo.
Heat shock proteins (Hsps) are stress proteins that mediate protein stabilization in various tissues and protect cells from environmental stress. Novel evidence suggests that overexpression of the small heat shock protein 27 (Hsp27) in neurons protects against neurotoxic stimuli and may act as an inhibitor of neurodegeneration. Overexpression of Hsps has been achieved by different means including pharmacological induction. Here, we show that intravitreal injection of the 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor simvastatin induces Hsp27 expression in axotomized retinal ganglion cells (RGCs) and enhances RGC survival 7 and 14 days after optic nerve (ON) axotomy by 90% and 19%, respectively. The flavonoid quercetin inhibited Hsp27 induction and abrogated simvastatin-mediated neuroprotection. Simvastatin increased Akt phosphorylation in vivo, indicating that the PI3K/Akt pathway contributes to central nervous system (CNS) protective effects achieved. We propose the use of statins as a feasible approach to reduce lesion-induced CNS neuronal degeneration in vivo.
Kretz
Alexandra
A
Neuroregeneration Laboratory, Department of Neurology, Friedrich-Schiller University, Erlanger Allee 101, D-07747 Jena, Germany.
Schmeer
Christian
C
Tausch
Svetlana
S
Isenmann
Stefan
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019771:Axotomy; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*
D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D011794:Quercetin; D019821:Simvastatin; D051057:Proto-Oncogene Proteins c-akt