Phosphorylation of 5-lipoxygenase at ser523 by protein kinase A determines whether pioglitazone and atorvastatin induce proinflammatory leukotriene B4 or anti-inflammatory 15-epi-lipoxin a4 production

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yumei YeYochai Birnbaum

Abstract

The 5-lipoxygenase (5LO) produces leukotriene B(4) and 15-epilipoxin-A(4) (15-epi-LXA(4)). Phosphorylation at Ser(523) by protein kinase A (PKA) prevents 5LO shift to the perinuclear membrane. Atorvastatin and pioglitazone up-regulate 15-epi-LXA(4) production in the heart. We assessed whether phosphorylation of 5LO by PKA determines whether 5LO interacts with the membranous cytosolic phospholipase A(2) (cPLA(2)) to produce leukotriene B(4) or with cyclooxygenase-2 (COX2) to produce 15-epi-LXA(4). Rats received either pioglitazone, atorvastatin, pioglitazone plus atorvastatin, vehicle, or LPS. Rat myocardial cells were incubated with pioglitazone plus atorvastatin, pioglitazone plus atorvastatin plus H-89 (PKA inhibitor), H-89, or vehicle for 8 h. Pioglitazone and atorvastatin did not affect total 5LO expression. However, both increased 5LO levels in the cytosolic fraction. H-89 caused a shift of 5LO to the membranous fraction in atorvastatin- and pioglitazone-treated rats. Pioglitazone and atorvastatin increased phospho-5LO levels. H-89 attenuated this increase. Both pioglitazone and atorvastatin increased COX2 levels in the cytosolic fraction and the membranous fraction. H-89 prevented this increase. Pioglitazone and atorvasta...Continue Reading

Associated Clinical Trials

Dec 30, 2009·Yochai Birnbaum, Yochai Birnbaum

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Citations

Mar 26, 2009·The Journal of Pharmacology and Experimental Therapeutics·Yolanda AlvarezNieves Fernández
Nov 13, 2010·Circulation Research·Matthew Spite, Charles N Serhan
Oct 30, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Yumei YeYochai Birnbaum
Jun 25, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nicholas S KirkbyJane A Mitchell
Nov 11, 2016·Cardiovascular Drugs and Therapy·Yochai BirnbaumYumei Ye
Aug 18, 2018·Therapeutic Advances in Neurological Disorders·Mingqin ZhuErik Hjorth
Sep 19, 2012·Metabolic Syndrome and Related Disorders·Yochai BirnbaumMandeep Bajaj
Sep 17, 2013·Fundamental & Clinical Pharmacology·Seyedeh Y SeyediMohammad Sharifzadeh
Sep 7, 2018·Frontiers in Microbiology·Rodrigo A López-MuñozJuan D Maya
Feb 10, 2012·Current Opinion in Clinical Nutrition and Metabolic Care·Erik Hjorth, Yvonne Freund-Levi
Sep 6, 2011·Basic Research in Cardiology·Yumei YeYochai Birnbaum
Mar 9, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Yumei YeYochai Birnbaum
Dec 10, 2015·Molecular Neurobiology·Mingqin ZhuMarianne Schultzberg
Dec 25, 2019·Oxidative Medicine and Cellular Longevity·Qian-Yi SunXiao-Yuan Mao
Jan 31, 2012·Current Atherosclerosis Reports·Yochai Birnbaum, Yumei Ye
Jul 17, 2020·Neurochemical Research·Zonglin HeYuechun Wang
Mar 2, 2021·Frontiers in Immunology·Stephania LibrerosCharles N Serhan
Jun 21, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Luciana P TavaresLirlândia P Sousa
Sep 4, 2010·The American Journal of Pathology·Charles N Serhan

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