title: Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease.
abstract: Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, function, substrate specificity and calcium requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2), Ca(2+)-independent (iPLA2), platelet activating factor acetylhydrolases (PAF-AH), lysosomal PLA2 (LyPLA2) and adipose specific PLA2 (AdPLA2). It is hypothesized that PLA2 can serve as pharmacological targets for the therapeutic treatment of several diseases, including cardiovascular diseases, atherosclerosis, immune disorders and cancer. Special emphasis has been placed on inhibitors of sPLA2 isoforms as pharmacological moieties, mostly due to the fact that these enzymes are activated during inflammatory events and because their expression is increased in several diseases. This review focuses on understanding how sPLA2 isoform expression is altered during disease progression and the possible therapeutic interventions to specifically target sPLA2 isoforms, including new approaches using nano-particulate-based strategies.
authors.affiliation: Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, United States.
authors.forename: Nhat D
authors.initials: ND
authors.lastname: Quach
authors.affiliation: Department of Drug Discovery & Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849-5503, United States.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Arnold
authors.affiliation: Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, United States. Electronic address: bsc@rx.uga.edu.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Cummings
mesh_terms: D000595:Amino Acid Sequence; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000628:therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000628:therapy; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology / Q000628:therapy; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D018805:Sepsis / Q000201:enzymology / Q000628:therapy; D017386:Sequence Homology, Amino Acid
chemical_list: D004791:Enzyme Inhibitors; D054497:Phospholipases A2, Secretory
keywords: Cell signaling; Interactomes; Liposomes; Nanoparticles; Phospholipase A(2) receptor; Secretory phospholipase A(2)