Aniracetam attenuates apoptosis of astrocytes subjected to simulated ischemia in vitro.
The aim of the present study was to establish whether aniracetam is capable of protecting cultured rat astrocytes against ischemic injury. Treatment of the cultures with aniracetam (1, 10 and 100 mM) during 24 h ischemia simulated in vitro significantly decreased the number of apoptotic cells. The antiapoptotic effects of the drug were confirmed by the increase of intracellular ATP and phosphocreatine (PCr) levels and the inhibition of the caspase-3 activity. Aniracetam also attenuated cellular oxidative stress by decreased production of reactive oxygen species (ROS). These effects were associated with the decrease in levels of c-fos and c-jun mRNA in primary astrocyte cultures exposed to 24 h ischemia. When cultured astrocytes were incubated during 24 h simulated ischemia with wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor or PD98059, a mitogen-activated protein (MAP)/extracellular signal regulated kinase (ERK) (MEK) inhibitor the cell apoptosis was accelerated. This effect was antagonized by adding 100 mM aniracetam to the culture medium. These findings suggest that the protective effect of aniracetam is mediated by PI 3-kinase and MEK pathways in the downstream mechanisms.
Gabryel
Bozena
B
Department of Pharmacology, Silesian Medical University, Katowice, Poland. bgabryel@interia.pl
Adamczyk
Jakub
J
Huzarska
Małgorzata
M
Pudełko
Anna
A
Trzeciak
Henryk I
HI
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects*; D002545:Brain Ischemia / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018697:Nootropic Agents / Q000494:pharmacology*; D010725:Phosphocreatine / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005452:Fluoresceins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D011760:Pyrrolidinones; D010725:Phosphocreatine; C037631:2',7'-dichlorofluorescein; C036466:aniracetam; D000255:Adenosine Triphosphate; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases