Activation of cPLA2 and sPLA2 in astrocytes exposed to simulated ischemia in vitro.
Both cytosolic PLA(2) (cPLA(2)) and secretory PLA(2) (sPLA(2)) have been implicated in pathology of cerebral ischemia. However, which of PLA(2) isoforms in astrocytes is responsible for arachidonic acid (AA) release contributing to their ischemic injury remains to be determined. The aim of the present study was to investigate the time-dependent activation of cPLA(2) and sPLA(2) in astrocytes exposed to combined oxygen glucose deprivation (OGD) as well as to evaluate the effectiveness of their pharmacological blockage as a method of preventing ischemic damage of the glial cells. It was shown that exposure of cultured astrocytes to OGD (0.5-24h) causes an increase in cPLA(2) and sPLA(2) expression and activity. The role of AA liberated mainly by cPLA(2) in the process of apoptosis was also demonstrated. To confirm the specific role of cPLA(2) and sPLA(2) in the mechanism of cells injury by OGD exposure, the effect of AACOCF(3) as cPLA(2) inhibitor and 12-epi-scalaradial as sPLA(2) inhibitor on AA release was examined. It was proved that simultaneous pharmacological blockade of enzymatic activity of cPLA(2) and sPLA(2) during OGD by AACOCF(3) and 12-epi-scalaradial substantially improves survival of ischemic injured glial cells.
Gabryel
Bozena
B
Department of Pharmacology, Medical University of Silesia, 18 Medyków Street, PL 40752 Katowice, Poland. bgabryel@interia.pl
Chalimoniuk
Malgorzata
M
Stolecka
Anna
A
Langfort
Jozef
J
D000818:Animals; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D001253:Astrocytes / Q000201:enzymology* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D004789:Enzyme Activation; D005947:Glucose / Q000172:deficiency; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2; D007511:Ischemia / Q000139:chemically induced / Q000473:pathology*; D010741:Phospholipases A / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D016718:Arachidonic Acid; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2; D053148:Caspase 3; D005947:Glucose