Lithium chloride, administered chronically to rats, does not affect the fractional phosphorylation of brain cytosolic phospholipase A2, while reducing its net protein level.
Lithium, used to treat bipolar disorder, has been reported to decrease rat brain mRNA and protein levels of cytosolic phospholipase A(2) (cPLA(2)), an enzyme that selectively hydrolyzes arachidonic acid from the stereospecifically numbered (sn)-2 position of membrane phospholipids, and to decrease PLA(2) activity. cPLA(2) can be activated by being phosphorylated at its Ser-228, Ser-505, and Ser-727 sites. In this study, we show that the percent phosphorylated cPLA(2) protein in rat brain is unaffected by lithium. Male Fischer-344 rats were fed lithium chloride for 6 weeks, so as to produce a therapeutically equivalent brain lithium concentration; control rats were fed lithium-free chow under parallel conditions. cPLA(2) was immunoprecipitated from brain homogenate and phosphorylated cPLA(2) protein was quantified using an anti-phosphoserine antibody, and compared to net cPLA(2) protein. The mean ratio of phosphorylated/total cPLA(2) was not changed significantly in the lithium-treated compared to the control group. Thus, decreased brain PLA(2) enzyme activity caused by chronic lithium is likely a consequence only of lithium's downregulation of cPLA(2) transcription.
Weerasinghe
Gayani R
GR
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Seemann
Ruth
R
Rapoport
Stanley I
SI
Bosetti
Francesca
F
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D010741:Phospholipases A / Q000032:analysis / Q000187:drug effects*; D054467:Phospholipases A2; D010766:Phosphorylation / Q000187:drug effects*; D011233:Precipitin Tests; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D018692:Antimanic Agents; D010741:Phospholipases A; D054467:Phospholipases A2; D018021:Lithium Chloride