title: A profile of NSAID-targeted arachidonic acid metabolisms in human embryonic stem cells (hESCs): implication of the negative effects of NSAIDs on heart tissue regeneration.
abstract: BACKGROUND
  An emerging technology using human embryonic stem cells (hESCs) to regenerate infarcted heart tissue has been underdeveloped. However, because non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are taken during the infarction, it becomes critical to know whether the NSAIDs have negative impacts on heart tissue regeneration when using hESCs.
  
  
  METHODS
  Mass spectrometry (LC/MS/MS) and high performance liquid chromatography (HPLC) analyses were used to analyze the functional presence of the elaborate prostanoids' biosynthesis and signaling systems in hESCs. The detected endogenous arachidonic acid (AA) released in the hESC membranes reflects the activity of phospholipase which directly controls the biosyntheses of the prostanoids.
  
  
  RESULTS
  The complete inhibition of the endogenous prostaglandin E(2) (PGE(2)) biosynthesis by the cyclooxygenase-2 (COX-2) inhibitor, NS398, confirmed that the major prostanoids synthesized in the hESCs are mediated by the COX-2 enzyme. We also found that PGE(2) and the prostacyclin (PGI(2)) metabolite, 6-keto-PGF(1α), are present in the undifferentiated hESCs.
  
  
  CONCLUSIONS
  This indicated different cyclooxygenase (COX)-downstream synthases and metabolizing enzymes are involved in the AA products' signaling through the COX-1 and COX-2 pathways. The presence of many enzymes' and receptors' [(COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), cytosolic prostaglandin E synthase (cPGES), prostaglandin I synthase (PGIS), the PGE(2) subtype receptors (EP(1), EP(2), and EP(4)) and the prostacyclin receptor (IP)] involvement in the prostanoid biosynthesis and activity was confirmed by western blot. The studies implied the negative effects of NSAIDs, such as aspirin and COX-2 inhibitors, which suppress prostanoid production during tissue regeneration for infarcted heart when using hESCs.
authors.affiliation: Center for Experimental Therapeutics and Pharmacoinformatics, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, United States.
authors.forename: Annirudha
authors.initials: A
authors.lastname: Chillar
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: So
authors.forename: Cheng-Huai
authors.initials: CH
authors.lastname: Ruan
authors.forename: Harnath
authors.initials: H
authors.lastname: Shelat
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
authors.forename: Ke-He
authors.initials: KH
authors.lastname: Ruan
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D061252:Feeder Cells / Q000187:drug effects / Q000378:metabolism; D006131:Growth Inhibitors / Q000009:adverse effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006131:Growth Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid