磷脂酶A2亚型作为预防和治疗的新靶点的炎症和肿瘤疾病

Title:Phospholipase A2 Isoforms as Novel Targets for Prevention and Treatment of Inflammatory and Oncologic Diseases

Volume: 17 Issue: 16

Author(s): Nagendra Sastry Yarla, Anupam Bishayee, Lakshmipathi Vadlakonda, Ramakrishna Chintala, Govinda Rao Duddukuri, Pallu Reddanna and Kaladhar S.V.G.K. Dowluru

Affiliation:

关键词: 磷脂酶A2、炎症、癌症、PLA2同种型特定抑制剂。

摘要: Phospholipase A2s (PLA2s) are group of enzymes, which cleave phospholipids specifically at sn-2 position to liberate free fatty acid, mostly arachidonic acid (AA) and lysophospholipids (LPLs). Inhibition of PLA2 prevents the liberation of AA and LPLs. Hence, researchers have been considering PLA2s could be a better therapeutic target than the downstream enzymes cyclooxygense and lipoxygenase. Several isoforms of PLA2s exist; they are mainly divided into secretory PLA2s (sPLA2), cytosolic PLA2s (cPLA2), and calcium independent PLA2s (iPLA2), platelet activating factor- acyl hydrolase (PAF-AH), lysosomal PLA2 (LPLA2), adipose-specific PLA2 (Ad- PLA). Each isoform of PLA2s is different in its chemical structure and physiological functions. sPLA2s (Groups IIA, V and X) are well characterized as proinflammatory mediating enzymes but their role in cancer is controversial. Groups IVA, IVB and IVC cPLA2s are present in humans but only Group IVA cPLA2 plays key role in pathophysiology of various cancers and inflammation. The role of iPLA2 in inflammation and cancer is limited. Lipoprotein associated PLA2 (Group VIIA PLA2), a PAF-AH isoform, has key role in atherosclerosis. Several isoform specific PLA2 inhibitors have been developed and some of the PLA2s inhibitors are currently under clinical trials for various inflammatory and oncologic diseases. This review focuses on the recent experimental evidences to support the notion that PLA2s are causally implicated in the pathobiology of cancer and inflammatory related disorders and discuss the potential utility of isoform specific PLA2 inhibitors as preventive and/or therapeutic agents.

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Nagendra Sastry Yarla, Anupam Bishayee, Lakshmipathi Vadlakonda, Ramakrishna Chintala, Govinda Rao Duddukuri, Pallu Reddanna and Kaladhar S.V.G.K. Dowluru , Phospholipase A2 Isoforms as Novel Targets for Prevention and Treatment of Inflammatory and Oncologic Diseases, Current Drug Targets 2016; 17 (16) . https://dx.doi.org/10.2174/1389450116666150727122501