Prostaglandin E(1) protects human liver sinusoidal endothelial cell from apoptosis induced by hypoxia reoxygenation.
Hepatic ischemia-reperfusion injury is an important cause of graft dysfunction after liver transplantation. Liver sinusoidal endothelial cells (LSECs) are particularly sensitive to ischemia-reperfusion injury and undergo apoptosis. This study investigates the protective role of PGE(1) on apoptosis of LSEC during hypoxia-reoxygenation in vitro. Hypothermia-hypoxia followed by reoxygenation triggered LSEC apoptosis, and prostaglandin PGE(1) protected LSEC from apoptosis in a dose-dependent manner. The release of matrix metalloproteinases (MMPs) and nitric oxide (NO) by LSECs were increased after hypoxia reoxygenation. Both the MMP inhibitor BB3103 and the NO inhibitor LNAM effectively decreased LSEC apoptosis, suggesting a separate role of MMPs and NO in hypoxia-reoxygenation-induced LSEC apoptosis. PGE(1) down-regulated NO production by inhibiting the expression of inducible NO synthase in LSEC. PGE(1) also inhibited MMP-2 release from LSEC during hypoxia reoxygenation. These results indicate that the protection of LSECs from apoptosis by PGE(1) in hepatic ischemia-reperfusion injury is mediated by inhibiting inducible NO synthase and MMP release.
Yang
Hong
H
Division of Investigative Surgery, Department of Surgery, University Hospital, University of Geneva, Geneva, Switzerland.
Majno
Pietro
P
Morel
Philippe
P
Toso
Christian
C
Triponez
Fréderic
F
Oberholzer
José
J
Mentha
Gilles
G
Lou
Jinning
J
D000527:Alprostadil / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D000527:Alprostadil; D010100:Oxygen