Rn. Li et Rs. El-mallahk, A novel evidence of different mechanisms of lithium and valproate neuroprotective action on human SY5Y neuroblastoma cells: caspase-3 dependency, NEUROSCI L, 294(3), 2000, pp. 147-150
Both lithium and valproate have been used in the treatment of manic-depress
ive illness with very limited understanding of their therapeutic mechanism
of action. Recent literature suggests that blocking of potassium channels m
ay be a common therapeutic mechanism of many antidepressant agents. To dete
rmine whether the commonly used antimanic agents could prevent potassium ef
flux-induced cell damage and apoptosis and the underlying mechanisms, we tr
eated SH-SY5Y human neuroblastoma cells with the potassium ionophore, valin
omycin (2-100 muM) and observed cell shrinkage, mitochondria damage, a sign
ificant increase in of lactate dehydrogenase (LDH) activity and caspase-3 p
rotein expression. Cells treated with lithium (0.5-3 mM) or valproate (0.07
-1.4 mM) alone produced no apoptotic morphological and biochemical changes
while both mood stabilizers pretreatment reduced or prevented the apoptotic
morphological changes. However, valinomycin-induced caspase-3 elevation wa
s only prevented by lithium pretreatment while both lithium and valproate a
ttenuated valinomycin-induced LDH release. Our results suggest that lithium
and valproate share a common neuroprotective action against potassium effl
ux-induced cell apoptosis with different mechanisms, (C) 2000 Elsevier Scie
nce Ireland Ltd. All rights reserved.