Correction: Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic phospholipase A2 in rat frontal cortex

Cytosolic phospholipase A2 (cPLA2) is thought to be the rate-limiting enzyme in the arachidonic acid/eicosanoid cascade. The ability of various agonists to increase steady-state cPLA2 mRNA levels has previously been reported. The current study delineates the contributions of transcriptional and post-transcriptional processes to the regulation of cPLA2 gene expression in response to a variety of agonists in cultured rat glomerular mesangial cells. Epidermal growth factor, platelet-derived growth factor, serum and phorbol myristate acetate all increase the half-life of cPLA2 mRNA transcripts, indicating a role for post-transcriptional modulation of gene expression. The presence of three ATTTA motifs in the 3′ untranslated region (3′UTR) of the rat cPLA2 cDNA is ascertained. Heterologous expression of chimeric constructs with different 3′UTRs ligated into the 3′ end of the luciferase coding region reveals that the presence of the cPLA2 3′UTR results in reduced luciferase activity compared with constructs without the cPLA2 3′UTR. Furthermore, the luciferase activity in the constructs with the cPLA2 3′UTR is increased in response to the same agonists which stabilize endogenous cPLA2 mRNA. A negligible effect of these agonists on transcriptional control of cPLA2 is evident using promoter-reporter constructs expressed in transient and stable transfectants. Taken together, these results indicate predominant post-transcriptional regulation of cPLA2 mRNA levels.

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Retraction note to: Chronic fluoxetine increases cytosolic phospholipase A2 activity and arachidonic acid turnover in brain phospholipids of the unanesthetized rat

Psychopharmacology ◽

10.1007/s00213-016-4499-z ◽

2016 ◽

Vol 234 (3) ◽

pp. 523-523

Author(s):

Ho-Joo Lee ◽

Jagadeesh S. Rao ◽

Renee N. Ertley ◽

Lisa Chang ◽

Stanley I. Rapoport ◽

...

Keyword(s):

Arachidonic Acid ◽

Phospholipase A2 ◽

Cytosolic Phospholipase A2 ◽

Cytosolic Phospholipase ◽

Brain Phospholipids ◽

Chronic Fluoxetine ◽

Phospholipase A2 Activity

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Negative regulation of cytosolic phospholipase A2 by melatonin in the rat pineal gland

Biochemical Journal ◽

10.1042/bj3510709 ◽

2000 ◽

Vol 351 (3) ◽

pp. 709-716 ◽

Cited By ~ 12

Author(s):

Beibei LI ◽

Hongjian ZHANG ◽

Mohammed AKBAR ◽

Hee-Yong KIM

Keyword(s):

Pineal Gland ◽

Phospholipase A2 ◽

Cytosolic Phospholipase A2 ◽

Mrna Levels ◽

Dependent Manner ◽

Melatonin Receptor ◽

Concentration Dependent Manner ◽

Cytosolic Phospholipase ◽

Rat Pineal Gland ◽

Melatonin Production

In this paper evidence that supports a new role for melatonin as a negative endogenous regulator of cytosolic phospholipase A2 (cPLA2) is presented. When rat pineal glands were incubated in culture, time-dependent release of arachidonic acid (AA) was observed, which was significantly inhibited by a known 85-kDa cPLA2 inhibitor, methyl arachidonyl fluorophosphonate. Co-incubation with melatonin inhibited the AA release in a concentration-dependent manner, and this decrease was accompanied by a reduction of cPLA2 protein and mRNA expression. Melatonin-receptor agonists, 2-iodo-N-butanoyl-5-methoxytryptamine and 5-methoxycarbonylamino-N-acetyltryptamine, also decreased AA release and cPLA2 protein and mRNA levels, while pre-incubation with the melatonin receptor antagonists luzindole and 2-phenylmelatonin abolished the melatonin effect. In vivo, as melatonin production reflected a typical diurnal variation, endogenous non-esterified AA and cPLA2 mRNA levels in the rat pineal gland showed an off-phase diurnal pattern in relation to melatonin levels. Intravenous administration of isoproterenol, which has been shown to elevate melatonin production, also decreased the levels of non-esterified AA and cPLA2 mRNA significantly. Direct administration of melatonin to rats by intravenous injection decreased the levels of non-esterified AA, cPLA2 protein and mRNA in rat pineal glands. In conclusion, melatonin endogenously down-regulates cPLA2 expression, presumably through melatonin-receptor-mediated processes.

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