title: Effects of 4-hydroxy-2-nonenal, a major lipid peroxidation-derived aldehyde, and N-acetylcysteine on the cyclooxygenase-2 expression in human uterine myometrium.
abstract: BACKGROUND
  Chorioamnionitis is one of the important causes of preterm labor. Preterm labor with chorioamnionitis is associated with oxidative stress. We reported that 4-hydroxy-2-nonenal (4-HNE), a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with chorioamnionitis. The aim of this study was to confirm the effect of 4-HNE on cyclooxygenase-2 (COX-2) and prostaglandin (PG) induction in the uterine myometrial tissues. We also examined the effect of N-acetylcysteine (NAC) on 4-HNE-induced COX-2 expression.
  
  
  METHODS
  Uterine myometrial tissues were obtained from 5 patients. One of them underwent elective cesarean section without labor, and 4 of them underwent hysterectomy because of placental previa or atonic bleeding. We stimulated the uterine myometrial tissues with 4-HNE. In addition, the tissues were pretreated with NAC before 4-HNE treatment. The expression of COX-2 mRNA was observed by real-time PCR. PGE2 and prostacyclin release into the supernatants of the tissue cultures was measured by ELISA.
  
  
  RESULTS
  4-HNE induced the COX-2 mRNA expression and PGE2 production in the uterine myometrial tissue culture in a dose-dependent and time-dependent manner. NAC inhibited 4-HNE-induced COX-2 expression.
  
  
  CONCLUSIONS
  4-HNE may play an important role in preterm labor. NAC might be protective against preterm labor under oxidative stress.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Temma-Asano
authors.forename: Ekaterine
authors.initials: E
authors.lastname: Tskitishvili
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanagawa
authors.forename: Takuji
authors.initials: T
authors.lastname: Tomimatsu
authors.forename: Tateki
authors.initials: T
authors.lastname: Tsutsui
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Yang Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakai
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shimoya
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009215:Myometrium / Q000201:enzymology*; D007752:Obstetric Labor, Premature / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D046509:Tissue Culture Techniques
chemical_list: D000447:Aldehydes; D012333:RNA, Messenger; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C027576:4-hydroxy-2-nonenal; D015232:Dinoprostone; D000111:Acetylcysteine