Wepy JA

References (2)

Title : Lysophospholipases cooperate to mediate lipid homeostasis and lysophospholipid signaling - Wepy_2019_J.Lipid.Res_60_360
Author(s) : Wepy JA , Galligan JJ , Kingsley PJ , Xu S , Goodman MC , Tallman KA , Rouzer CA , Marnett LJ
Ref : J Lipid Res , 60 :360 , 2019
Abstract : Lysophospholipids (LysoPLs) are bioactive lipid species involved in cellular signaling processes and the regulation of cell membrane structure. LysoPLs are metabolized through the action of lysophospholipases, including lysophospholipase A1 (LYPLA1) and lysophospholipase A2 (LYPLA2). A new X-ray crystal structure of LYPLA2 compared with a previously published structure of LYPLA1 demonstrated near-identical folding of the two enzymes; however, LYPLA1 and LYPLA2 have displayed distinct substrate specificities in recombinant enzyme assays. To determine how these in vitro substrate preferences translate into a relevant cellular setting and better understand the enzymes' role in LysoPL metabolism, CRISPR-Cas9 technology was utilized to generate stable KOs of Lypla1 and/or Lypla2 in Neuro2a cells. Using these cellular models in combination with a targeted lipidomics approach, LysoPL levels were quantified and compared between cell lines to determine the effect of losing lysophospholipase activity on lipid metabolism. This work suggests that LYPLA1 and LYPLA2 are each able to account for the loss of the other to maintain lipid homeostasis in cells; however, when both are deleted, LysoPL levels are dramatically increased, causing phenotypic and morphological changes to the cells.
ESTHER : Wepy_2019_J.Lipid.Res_60_360
PubMedSearch : Wepy_2019_J.Lipid.Res_60_360
PubMedID: 30482805
Gene_locus related to this paper: human-LYPLA2

Title : Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells - Manna_2014_J.Biol.Chem_289_33741
Author(s) : Manna JD , Wepy JA , Hsu KL , Chang JW , Cravatt BF , Marnett LJ
Ref : Journal of Biological Chemistry , 289 :33741 , 2014
Abstract : Prostaglandin glycerol esters (PG-Gs) are produced as a result of the oxygenation of the endocannabinoid, 2-arachidonoylglycerol, by cyclooxygenase 2. Understanding the role that PG-Gs play in a biological setting has been difficult because of their sensitivity to enzymatic hydrolysis. By comparing PG-G hydrolysis across human cancer cell lines to serine hydrolase activities determined by activity-based protein profiling, we identified lysophospholipase A2 (LYPLA2) as a major enzyme responsible for PG-G hydrolysis. The principal role played by LYPLA2 in PGE2-G hydrolysis was confirmed by siRNA knockdown. Purified recombinant LYPLA2 hydrolyzed PG-Gs in the following order of activity: PGE2-G > PGF2alpha-G > PGD2-G; LYPLA2 hydrolyzed 1- but not 2-arachidonoylglycerol or arachidonoylethanolamide. Chemical inhibition of LYPLA2 in the mouse macrophage-like cell line, RAW264.7, elicited an increase in PG-G production. Our data indicate that LYPLA2 serves as a major PG-G hydrolase in human cells. Perturbation of this enzyme should enable selective modulation of PG-Gs without alterations in endocannabinoids, thereby providing a means to decipher the unique functions of PG-Gs in biology and disease.
ESTHER : Manna_2014_J.Biol.Chem_289_33741
PubMedSearch : Manna_2014_J.Biol.Chem_289_33741
PubMedID: 25301951
Gene_locus related to this paper: human-LYPLA2