4.7 Article Retracted Publication

被撤回的出版物: Decrease in the AP-2 DNA-binding activity and in the protein expression of AP-2 α and AP-2 β in frontal cortex of rats treated with lithium for 6 weeks (Retracted article. See vol. 42, pg. 456, 2018)

期刊

NEUROPSYCHOPHARMACOLOGY
卷 30, 期 11, 页码 2006-2013

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1300740

关键词

brain; lithium; transcription factors; PKC; AP-2; AP-1

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Lithium chloride (LiCl), when fed to rats for 6 weeks, has been reported to decrease brain mRNA, protein, and activity levels of arachidonic acid (AA)-selective cytosolic phospholipase A(2) (cPLA(2)), without affecting secretory sPLA(2) or Ca2+-independent iPLA(2) We investigated whether transcription factors known to regulate cPLA(2) gene expression are modulated by chronic lithium treatment. Male Fischer-344 rats were fed a LiCl-containing diet for 6 weeks to produce a therapeutically relevant brain lithium concentration. Control animals were fed a LiCl-free diet. Using a gelshift assay, we found that LiCl significantly decreased activating protein 2 (AP-2)-binding activity, and protein levels of the AP-2 alpha and AP-2 beta but not of the AP-2 gamma subunits in the frontal cortex. Activating protein 1 (AP- 1)binding activity was increased, whereas glucocorticoid response element, polyoma enhancer activator 3, and nuclear factor kappa B DNA-binding activities were not changed significantly, Since both cPLA(2) and AP-2 can be activated by protein kinase C (PKC), we examined the frontal cortex protein levels of PKC alpha and PKC epsilon, as well as AA-dependent PKC activity. The protein levels of PKC alpha and PKC e were decreased significantly, as was AA-dependent PKC activity, in the lithium-treated compared to control rats, Our results suggest that the reported decrease in brain gene expression of cPLA(2) by chronic lithium may be mediated by reduced AP-2 transcriptional activity, and that decreased expression of PKC a and PKC e. contributes to lowering the AP-2 activity.

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