title: Calcium-independent phospholipases A2 and their roles in biological processes and diseases.
abstract: Among the family of phospholipases A2 (PLA2s) are the Ca(2+)-independent PLA2s (iPLA2s) and they are designated group VI iPLA2s. In relation to secretory and cytosolic PLA2s, the iPLA2s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA2s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca(2+) for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membrane-associated iPLA2γ) and PNPLA9 (cytosol-associated iPLA2β) are the most widely studied and understood. The iPLA2s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA2s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA2s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA2s and discussion of the potential mechanisms of action of the iPLA2s and related involved lipid mediators.
authors.affiliation: Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Sasanka
authors.initials: S
authors.lastname: Ramanadham
authors.affiliation: Undergraduate Research Office, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Tomader
authors.initials: T
authors.lastname: Ali
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Ashley
authors.affiliation: Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Bone
authors.affiliation: Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: William D
authors.initials: WD
authors.lastname: Hancock
authors.affiliation: Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Lei
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D020816:Amino Acid Motifs / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008049:Lipase; D054512:Phospholipases A2, Calcium-Independent; D002118:Calcium
keywords: alternate splicing; arachidonic acid; cancers; central nervous system disorders; docosahexaenoic acid; eicosanoids; immune responses; inflammation; membrane homeostasis; signaling; β-cells