Open AccessDifferent mechanisms of protection against apoptosis by valproate and Li +
Author(s) -
Mora Alfonso,
GonzálezPolo Rosa A.,
Fuentes José M.,
Soler Germán,
Centeno Francisco
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00919.x
Subject(s) - phosphatidylinositol , neuroprotection , ly294002 , apoptosis , chemistry , signal transduction , microbiology and biotechnology , kinase , phosphatidylinositol 4,5 bisphosphate , pharmacology , pi3k/akt/mtor pathway , biochemistry , biology
Acute treatment with valproate and Li + was found to protect cultured cerebellar granule cells against apoptosis induced by low K + (5 m m ). Because the protection was unaffected by MK801 ( N ‐methyl‐ d ‐aspartate receptor inhibitor), an increase in glutamate release cannot be responsible for the observed neuroprotection. Insulin also protects against low‐K + ‐induced apoptosis of cerebellar granule cells. This protection is totally dependent on LY294002 (a phosphatidylinositol 3‐kinase inhibitor). These results suggest a role for phosphatidylinositol 3‐kinase in the neuroprotection induced by insulin. Likewise, and in contrast with the results observed with Li + , the protection induced by valproate is also dependent on insulin and LY294002. Moreover, valproate (a branched‐chain fatty acid) does not change the plasma membrane microviscosity under physiological conditions. These results suggest that valproate protects against low‐K + ‐induced apoptosis by acting in the phosphatidylinositol 3‐kinase/protein kinase B pathway. The protection by Li + is independent of this transduction pathway.