Role of hemin in the modulation of XXXX -mediated endothelial cell injury.

@entity1 @entity137 @entity274 @entity44024 @entity13975 @entity1317 @entity291 @entity1446
Heme oxygenase (HO) has been primarily regarded as the rate-limiting enzyme in the degradation of @entity1446 . However it has recently been proposed that the inducible isoform, @entity13975 (EC 1.14.99.3), functions as a stress-responsive antioxidant enzyme, with the capacity to protect against oxidant-mediated @entity1317 . This study used an in vitro model of endothelial permeability to determine the effects of the @entity13975 -inducing agent hemin on noncytotoxic endothelial injury mediated by acute oxidant stress. Effects of hemin on oxidant-mediated @entity137 in a number of endothelial cell types were also investigated. A 20-min exposure of @entity1 umbilical vein endothelial cell (HUVEC) monolayers to @entity274 resulted in a significant concentration-dependent increase in permeability, which was reversible 48 h later. Pretreatment of monolayers with hemin for 2 h followed by 18 h in complete medium resulted in @entity13975 induction and the attenuation of @entity274 -mediated increases in endothelial permeability, and significantly improved the restoration of endothelial barrier function 48 h later. In HUVEC and in the @entity1 microvascular endothelial cell line HMEC-1, hemin treatment as above resulted in protection against @entity137 , but not in @entity291 aortic endothelial cells (BAECs), where such @entity137 was potentiated. This potentiation was inhibited by incubation with the HO inhibitor @entity44024 , supporting a role for @entity13975 in the potentiation of the cytotoxic response. When the exposure time of BAEC to hemin was extended to 24 h, @entity274 -mediated @entity137 was attenuated. We conclude that hemin treatment is cytoprotective against noncytotoxic endothelial injury in vitro, under conditions that may not offer global protection against cytotoxic @entity1317 . This would indicate that @entity13975 induction associated with @entity137 in vivo is not always beneficial and therefore that the use of hemin as a therapeutic agent to offset oxidant injury in vascular endothelium should be undertaken with caution.
