title: Regulation of Calcium-Independent Phospholipase A2 Expression by Adrenoceptors and Sterol Regulatory Element Binding Protein-Potential Crosstalk Between Sterol and Glycerophospholipid Mediators.
abstract: Calcium-independent phospholipase A2 (iPLA2) is an 85-kDa enzyme that releases docosahexaenoic acid (DHA) from glycerophospholipids. DHA can be metabolized to resolvins and neuroprotectins that have anti-inflammatory properties and effects on neural plasticity. Recent studies show an important role of prefrontal cortical iPLA2 in hippocampo-prefrontal cortical LTP and antidepressant-like effect of the norepinephrine reuptake inhibitor (NRI) antidepressant, maprotiline. In this study, we elucidated the cellular mechanisms through which stimulation of adrenergic receptors could lead to increased iPLA2 expression. Treatment of SH-SY5Y neuroblastoma cells with maprotiline, another tricyclic antidepressant with noradrenaline reuptake inhibiting properties, nortriptyline, and the adrenergic receptor agonist, phenylephrine, resulted in increased iPLA2β mRNA expression. This increase was blocked by inhibitors to alpha-1 adrenergic receptor, mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) 1/2, and sterol regulatory element-binding protein (SREBP). Maprotiline and phenylephrine induced binding of SREBP-2 to sterol regulatory element (SRE) region on the iPLA2 promoter, as determined by electrophoretic mobility shift assay (EMSA). Together, results indicate that stimulation of adrenoreceptors causes increased iPLA2 expression via MAP kinase/ERK 1/2 and SREBP, and suggest a possible mechanism for effect of CNS noradrenaline on neural plasticity and crosstalk between sterol and glycerophospholipid mediators, that may play a role in physiological or pathophysiological processes in the brain and other organs.
authors.affiliation: Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
authors.forename: Wee-Siong
authors.initials: WS
authors.lastname: Chew
authors.affiliation: Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore. antongwy@nus.edu.sg.|Neurobiology and Ageing Research Programme, National University of Singapore, Singapore, 119260, Singapore. antongwy@nus.edu.sg.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Ong
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020404:Glycerophospholipids / Q000502:physiology*; D054522:Group VI Phospholipases A2 / Q000096:biosynthesis*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008376:Maprotiline / Q000494:pharmacology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000502:physiology*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism
chemical_list: D000322:Adrenergic Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000928:Antidepressive Agents; D020404:Glycerophospholipids; D011941:Receptors, Adrenergic; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D013261:Sterols; D008376:Maprotiline; D048049:Extracellular Signal-Regulated MAP Kinases; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: Cholesterol; Exercise; Fat; Fatty acids; Glycerophospholipids; Noradrenaline; Norepinephrine; Obesity; Synaptic plasticity