Thiazolidinediones increase arachidonic acid release and subsequent prostanoid production in a peroxisome proliferator-activated receptor γ-independent manner

Hiroki Tsukamoto, Takanori Hishinuma, Naoto Suzuki, Risa Tayama, Masahiro Hiratsuka, Yoshihisa Tomioka, Michinao Mizugaki, Junichi Goto

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Thiazolidinedione, peroxisome proliferator-activated receptor γ (PPARγ) agonist, has been used as an anti-diabetic drug and as an useful tool to elucidate multiple PPARγ functions by in vitro and in vivo studies. We investigated the effects of thiazolidinediones on prostanoid production in lipopolysaccharide-stimulated cells. The high concentrations (>10 μM) of rosiglitazone and pioglitazone significantly increased lipopolysaccharide-stimulated prostanoid production such as thromboxane A2 and prostaglandin E2. However, PPARγ antagonist could not inhibit them. In PPARγ-deficient cells, thiazolidinediones increased prostaglandin E2 production. Thiazolidinediones increased arachidonic acid (AA) release from the cell membrane by not stimulating AA releasing process involving several phospholipase A2s but inhibiting AA reuptaking process. The expression of cyclooxygenase-1 and cyclooxygenase-2 were not affected by thiazolidinediones. In this study, we demonstrated that high concentrations of TZDs increased AA release by the inhibition of AA reuptaking process, leading to subsequent increase in the prostanoid production in a PPARγ-independent manner. This mechanism provides useful information for the elucidation of multiple PPARγ functions and diabetic drug therapy.

Original languageEnglish
Pages (from-to)191-213
Number of pages23
JournalProstaglandins and Other Lipid Mediators
Volume73
Issue number3-4
DOIs
Publication statusPublished - 2004 Apr

Keywords

  • Arachidonic acid
  • PPARγ
  • Prostaglandin
  • Thiazolidinedione
  • Thromboxane

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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