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标题：Calcium-independent phospholipases A2 and their roles in biological processes and diseases
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作者：Sasanka Ramanadham ; Tomader Ali ; Jason W. Ashley 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2015
卷号：56
期号：9
页码：1643-1668
DOI：10.1194/jlr.R058701
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Among the family of phospholipases A₂ (PLA₂s) are the Ca²⁺-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 Ca²⁺ 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.
关键词：signaling ; membrane homeostasis ; arachidonic acid ; eicosanoids ; docosahexaenoic acid ; inflammation ; immune responses ; alternate splicing ; β-cells ; central nervous system disorders ; cancers