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Lithium inhibits caspase 3 activation and dephosphorylation of PKB and GSK3 induced by K + deprivation in cerebellar granule cells
Author(s) -
Mora Alfonso,
Sabio Guadalupe,
GonzálezPolo Rosa A.,
Cuenda Ana,
Alessi Dario R.,
Alonso Juan C.,
Fuentes José M.,
Soler Germán,
Centeno Francisco
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00410.x
Subject(s) - dephosphorylation , chemistry , protein kinase b , kinase , potassium , phosphorylation , microbiology and biotechnology , gsk 3 , caspase 3 , phosphatase , glycogen synthase , phosphatidylinositol , lithium (medication) , biochemistry , apoptosis , biology , endocrinology , programmed cell death , organic chemistry
Lithium protects cerebellar granule cells from apoptosis induced by low potassium, and also from other apoptotic stimuli. However, the precise mechanism by which this occurs is not understood. When cerebellar granule cells were switched to low potassium medium, the activation of caspase 3 was detected within 6 h, suggesting a role of caspase 3 in mediating apoptosis under conditions of low potassium. In the same conditions, lithium (5 m m ) inhibited the activation of caspase 3 induced by low potassium. As lithium did not inhibit caspase 3 activity in vitro , these results suggest that this ion inhibits an upstream component that is required for caspase 3 activation. Lithium is known to inhibit a kinase termed glycogen sythase kinase 3 (GSK3), which is implicated in the survival pathway of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/PKB). Here we demonstrate that low potassium in the absence of lithium induces the dephosphorylation, and therefore the activation, of GSK3. However, when lithium was present, GSK3 remained phosphorylated at the same level as observed under conditions of high potassium. Low potassium induced the dephosphorylation and inactivation of PKB, whereas when lithium was present PKB was not dephosphorylated. Our results allow us to propose a new hypothesis about the action mechanism of lithium, this ion could inhibit a serine‐threonine phosphatase induced by potassium deprivation.