title: The Effects of Heme Oxygenase By-Products on the Proliferation and Invasion of HUVECs, HTR-8/SVneo Cells, 3A(tPA 30-1) Cells, and HESCs Under Varying Oxygen Concentrations.
abstract: OBJECTIVE
  Abnormal spiral artery remodeling during early pregnancy leads to preeclampsia. The proliferation and invasion of trophoblasts in pregnancy are important for spiral artery remodeling. This study examined whether heme oxygenase (HO) by-products (carbon monoxide biliverdin, and iron) play roles in regulating the restoration of proliferation and invasion of human umbilical vein endothelial cells (HUVECs), HTR-8/SV-neo cells originating from first-trimester trophoblasts, 3A(tPA 30-1) obtained from term trophoblasts, and human endometrial stromal cells (HESCs) inhibited by zinc protoporphyrin IX (Znpp-9).
  
  
  METHODS
  We explored whether HO by-products restored the proliferation and invasion of HUVECs, HTR-8/SVneo cells, 3A(tPA 30-1) cells, and HESCs inhibited by Znpp-9 depending on the oxygen concentration.
  
  
  RESULTS
  Bilirubin promoted proliferation of HUVECs, HTR-8/SVneo cells, 3A(tPA-30-1) cells, and HESCs under both hypoxic and normoxic conditions. Biliverdin also promoted invasion of HUVECs, HTR-8/SVneo cells, 3A(tPA30-1) cells, and HESCs under both hypoxic and normoxic conditions. Carbon monoxide-releasing molecule 2 promoted the proliferation and invasion of specific cell types depending on the oxygen concentration.
  
  
  CONCLUSIONS
  Our data suggest that HO by-products differentially stimulate the proliferation and invasion of cells involved in pregnancy maintenance. When HO by-products are considered to be stimulants during the invasion and proliferation of such cells, both target cells and the gestational period should be considered.
authors.affiliation: Department of Obstetrics and Gynecology, Eulji University Hospital, Daejeon, Korea.
authors.forename: Joong Gyu
authors.initials: JG
authors.lastname: Ha
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Dong heon
authors.initials: Dh
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Sung hun
authors.initials: Sh
authors.lastname: Na
authors.affiliation: Department of Molecular and Cell Biochemistry, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Kwon Soo
authors.initials: KS
authors.lastname: Ha
authors.affiliation: Department of Molecular and Cell Biochemistry, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea rapidhwang@kangwon.ac.kr.
authors.forename: Jong Yun
authors.initials: JY
authors.lastname: Hwang
mesh_terms: D001663:Bilirubin / Q000378:metabolism / Q000494:pharmacology*; D001664:Biliverdine / Q000378:metabolism / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000378:metabolism; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011247:Pregnancy; D011524:Protoporphyrins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D011524:Protoporphyrins; C447082:tricarbonyldichlororuthenium (II) dimer; C017803:zinc protoporphyrin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine; D001663:Bilirubin; D010100:Oxygen
keywords: biliverdin; carbon monoxide; heme oxygenase; heme oxygenase by-products; trophoblast