BACKGROUND: Skin injury leads to the release of heme, a potent prooxidant which is degraded by heme oxygenase-1 (HO-1) to carbon monoxide, iron, and biliverdin, subsequently reduced to bilirubin. Recently the involvement of HO-1 in angiogenesis has been shown; however, the role of heme and HO-1 in wound healing angiogenesis has not been yet investigated. RESULTS: Treatment of HaCaT keratinocytes with hemin (heme chloride) induced HO-1 expression and activity. The effect of heme on vascular endothelial growth factor (VEGF) synthesis is variable: induction is significant after a short, 6 h treatment with heme, while longer stimulation may attenuate its production. The involvement of HO-1 in VEGF synthesis was confirmed by inhibition of VEGF expression by SnPPIX, a blocker of HO activity and by attenuation of HO-1 mRNA expression with specific siRNA. Importantly, induction of HO-1 by hemin was able to overcome the inhibitory effect of high glucose on VEGF synthesis. Moreover, HO-1 expression was also induced in keratinocytes cultured in hypoxia, with concomitant augmentation of VEGF production, which was further potentiated by hemin stimulation. Accordingly, conditioned media from keratinocytes overexpressing HO-1 enhanced endothelial cell proliferation and augmented formation of capillaries in angiogenic assay in vitro. CONCLUSIONS: HO-1 is involved in hemin-induced VEGF expression in HaCaT and may play a role in hypoxic regulation of this protein. HO-1 overexpression may be beneficial in restoring the proper synthesis of VEGF disturbed in diabetic conditions.
BACKGROUND:Skin injury leads to the release of heme, a potent prooxidant which is degraded by heme oxygenase-1 (HO-1) to carbon monoxide, iron, and biliverdin, subsequently reduced to bilirubin. Recently the involvement of HO-1 in angiogenesis has been shown; however, the role of heme and HO-1 in wound healing angiogenesis has not been yet investigated. RESULTS: Treatment of HaCaT keratinocytes with hemin (heme chloride) induced HO-1 expression and activity. The effect of heme on vascular endothelial growth factor (VEGF) synthesis is variable: induction is significant after a short, 6 h treatment with heme, while longer stimulation may attenuate its production. The involvement of HO-1 in VEGF synthesis was confirmed by inhibition of VEGF expression by SnPPIX, a blocker of HO activity and by attenuation of HO-1 mRNA expression with specific siRNA. Importantly, induction of HO-1 by hemin was able to overcome the inhibitory effect of high glucose on VEGF synthesis. Moreover, HO-1 expression was also induced in keratinocytes cultured in hypoxia, with concomitant augmentation of VEGF production, which was further potentiated by hemin stimulation. Accordingly, conditioned media from keratinocytes overexpressing HO-1 enhanced endothelial cell proliferation and augmented formation of capillaries in angiogenic assay in vitro. CONCLUSIONS:HO-1 is involved in hemin-induced VEGF expression in HaCaT and may play a role in hypoxic regulation of this protein. HO-1 overexpression may be beneficial in restoring the proper synthesis of VEGF disturbed in diabetic conditions.
Authors: Anna T Grazul-Bilska; Mary Lynn Johnson; Jerzy J Bilski; Dale A Redmer; Lawrence P Reynolds; Ahmed Abdullah; Kay M Abdullah Journal: Drugs Today (Barc) Date: 2003-10 Impact factor: 2.245
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Authors: G Balla; H S Jacob; J Balla; M Rosenberg; K Nath; F Apple; J W Eaton; G M Vercellotti Journal: J Biol Chem Date: 1992-09-05 Impact factor: 5.157
Authors: Anke Schmidt; Stephan Dietrich; Anna Steuer; Klaus-Dieter Weltmann; Thomas von Woedtke; Kai Masur; Kristian Wende Journal: J Biol Chem Date: 2015-01-14 Impact factor: 5.157
Authors: Magdalena Kozakowska; Maciej Ciesla; Anna Stefanska; Klaudia Skrzypek; Halina Was; Agnieszka Jazwa; Anna Grochot-Przeczek; Jerzy Kotlinowski; Agnieszka Szymula; Aleksandra Bartelik; Milena Mazan; Oleksandr Yagensky; Urszula Florczyk; Krzysztof Lemke; Anna Zebzda; Grzegorz Dyduch; Witold Nowak; Krzysztof Szade; Jacek Stepniewski; Marcin Majka; Rafal Derlacz; Agnieszka Loboda; Jozef Dulak; Alicja Jozkowicz Journal: Antioxid Redox Signal Date: 2011-10-19 Impact factor: 8.401