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Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells.
J Biol Chem. 2014 Dec 05; 289(49):33741-53.JB

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 > PGF2α-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.

Authors+Show Affiliations

From the A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and.From the A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and.the Skaggs Institute for Chemical Biology and the Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037.the Skaggs Institute for Chemical Biology and the Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037.the Skaggs Institute for Chemical Biology and the Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037.From the A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and larry.marnett@vanderbilt.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25301951

Citation

Manna, Joseph D., et al. "Identification of the Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells." The Journal of Biological Chemistry, vol. 289, no. 49, 2014, pp. 33741-53.
Manna JD, Wepy JA, Hsu KL, et al. Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells. J Biol Chem. 2014;289(49):33741-53.
Manna, J. D., Wepy, J. A., Hsu, K. L., Chang, J. W., Cravatt, B. F., & Marnett, L. J. (2014). Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells. The Journal of Biological Chemistry, 289(49), 33741-53. https://doi.org/10.1074/jbc.M114.582353
Manna JD, et al. Identification of the Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells. J Biol Chem. 2014 Dec 5;289(49):33741-53. PubMed PMID: 25301951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells. AU - Manna,Joseph D, AU - Wepy,James A, AU - Hsu,Ku-Lung, AU - Chang,Jae Won, AU - Cravatt,Benjamin F, AU - Marnett,Lawrence J, Y1 - 2014/10/09/ PY - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/3/4/medline KW - Activity-based Protein Profiling KW - Cancer KW - Chemical Biology KW - Endocannabinoids KW - Enzyme Kinetics KW - Lipid Metabolism KW - Prostaglandin KW - Prostaglandin Glycerol Esters KW - Serine Hydrolase SP - 33741 EP - 53 JF - The Journal of biological chemistry JO - J Biol Chem VL - 289 IS - 49 N2 - 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 > PGF2α-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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/25301951/Identification_of_the_major_prostaglandin_glycerol_ester_hydrolase_in_human_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)47326-0 DB - PRIME DP - Unbound Medicine ER -