Role of heme oxygenase-1 in hydrogen peroxide-induced VEGF synthesis: effect of HO-1 knockout.
Hydrogen peroxide is an important mediator of intracellular signaling, which potently enhances the expression of heme oxygenase-1 (HO-1) and upregulates synthesis of vascular endothelial growth factor (VEGF). The purpose of the present study was to explore the involvement of HO-1 in regulation of H(2)O(2)-mediated induction of VEGF synthesis. We provide genetic evidence that basal and H(2)O(2)-induced VEGF synthesis is partially dependent on HO-1. Inhibition of HO-1 activity by tin protoporphyrin (SnPPIX) resulted in downregulation of VEGF synthesis in murine fibroblasts and human keratinocytes. The relationship between HO-1 and VEGF was corroborated by using cells derived from HO-1 knockout mice, which demonstrated lower basal and H(2)O(2)-induced production of VEGF. Additionally, knock out of HO-1 gene impaired induction of VEGF by hemin, lysophosphatidylcholine, and prostaglandin-J(2). Our results provide confirmation for the involvement of HO-1 in regulation of angiogenesis.
Cisowski
Jarosław
J
Faculty of Biotechnology, Jagiellonian University, Kraków, Poland.
Loboda
Agnieszka
A
Józkowicz
Alicja
A
Chen
Sifeng
S
Agarwal
Anupam
A
Dulak
Józef
J
D000818:Animals; D001011:Aorta / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse