التفاصيل البيبلوغرافية
| العنوان: |
Effect of heme and heme oxygenase-1 on vascular endothelial growth factor synthesis and angiogenic potency of human keratinocytes |
| المؤلفون: |
Jazwa, Agnieszka1, Loboda, Agnieszka1, Golda, Slawomir1, Cisowski, Jaroslaw1, Szelag, Magdalena1, Zagorska, Anna1, Sroczynska, Patrycja1, Drukala, Justyna2, Jozkowicz, Alicja1, Dulak, Jozef1 jdulak@mol.uj.edu.pl |
| المصدر: |
Free Radical Biology & Medicine. Apr2006, Vol. 40 Issue 7, p1250-1263. 14p. |
| مصطلحات موضوعية: |
*HEME oxygenase, *VASCULAR endothelial growth factors, *KERATINOCYTES, *CARBON monoxide |
| مستخلص: |
Abstract: 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. [Copyright &y& Elsevier] |
| قاعدة البيانات: |
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