Activation of arachidonic acid-specific phospholipase A2 in human neuroblastoma cells after chronic alcohol exposure: prevention by GM1 ganglioside.
Human neuroblastoma cells were exposed to ethanol (EtOH; 100 mM) in culture for various time periods. It was found that chronic EtOH exposure increased the arachidonyl-specific phospholipase A2 (PLA2) activity significantly in both cytosol (1.6-fold) and membrane (2.2-fold) fractions when 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine was used as a substrate. This arachidonyl-specific PLA2 activity progressively increased with increasing duration of EtOH exposure and reached peak level at 72-hr EtOH exposure (chronic). A significant amount of the PLA2 activity was associated with the membrane fraction. No significant difference in PLA2 activity was observed when 1-palmitoyl-2 oleoyl or linoleoyl-sn-glycero-3-phosphocholine was used as a substrate. It was also found that co-treatment of neuroblastoma cells with ganglioside GM1 reduced the EtOH-induced activation of arachidonyl-specific PLA2 activity. The present results indicate that arachidonic acid-specific PLA2 may play a role in adaptation mechanisms to chronic EtOH in cultured neuroblastoma cells. Ganglioside GM1, in part, may exert its neuroprotective effects by modulating arachidonyl-specific PLA2 activity in chronic EtOH-exposed neuroblastoma cells.
Basavarajappa
B S
BS
Division of Analytical Psychopharmacology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Saito
M
M
Cooper
T B
TB
Hungund
B L
BL
D016718:Arachidonic Acid / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
D016718:Arachidonic Acid; D005677:G(M1) Ganglioside; D010741:Phospholipases A; D054467:Phospholipases A2