Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

10.1038/88842 ◽  
2001 ◽  
Vol 28 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Bert Oosthuyse ◽  
Lieve Moons ◽  
Erik Storkebaum ◽  
Heike Beck ◽  
Dieter Nuyens ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Motor Neuron ◽  
Vascular Endothelial ◽  
Hypoxia Response Element ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Response Element ◽  
Hypoxia Response ◽  
Endothelial Growth Factor

Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 189-197 ◽  
Author(s):  
Hideo Kimura ◽  
Alessandro Weisz ◽  
Yukiko Kurashima ◽  
Kouichi Hashimoto ◽  
Tsutomu Ogura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Hypoxia Response Element ◽  
Response Element ◽  
Hypoxia Response ◽  
Hypoxia Inducible Factor 1 ◽  
Endothelial Growth Factor

Abstract Nitric oxide (NO) regulates production of vascular endothelial growth factor (VEGF) by normal and transformed cells. We demonstrate that NO donors may up-regulate the activity of the human VEGF promoter in normoxic human glioblastoma and hepatoma cells independent of a cyclic guanosine monophosphate–mediated pathway. Deletion and mutation analysis of the VEGF promoter indicates that the NO-responsive cis-elements are the hypoxia-inducible factor-1 (HIF-1) binding site and an adjacent ancillary sequence that is located immediately downstream within the hypoxia-response element (HRE). This work demonstrates that the HRE of this promoter is the primary target of NO. In addition, VEGF gene regulation by NO, as well as by hypoxia, is potentiated by the AP-1 element of the gene. Our study also reveals that NO and hypoxia induce an increase in HIF-1 binding activity and HIF-1 protein levels, both in the nucleus and the whole cell. These results suggest that there are common features of the NO and hypoxic pathways of VEGF induction, while in part, NO mediates gene transcription by a mechanism distinct from hypoxia. This is demonstrated by a difference in sensitivity to guanylate cyclase inhibitors and a different pattern of HIF-1 binding. These results show that there is a primary role for NO in the control of VEGF synthesis and in cell adaptations to hypoxia. (Blood. 2000;95:189-197)

Effects of vascular endothelial growth factor (VEGF) on motor neuron degeneration

2004 ◽  
Vol 17 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Ludo Van Den Bosch ◽  
Erik Storkebaum ◽  
Vicky Vleminckx ◽  
Lieve Moons ◽  
Ludo Vanopdenbosch ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Motor Neuron ◽  
Vascular Endothelial ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Endothelial Growth Factor

scholarly journals Vascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degeneration

2009 ◽  
Vol 69 (13) ◽  
pp. 871-884 ◽  
Author(s):  
J. Simon Lunn ◽  
Stacey A. Sakowski ◽  
Bhumsoo Kim ◽  
Andrew A. Rosenberg ◽  
Eva L. Feldman
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Motor Neuron ◽  
Vascular Endothelial ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Endothelial Growth Factor ◽  
G93a Sod1

Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 189-197 ◽  
Author(s):  
Hideo Kimura ◽  
Alessandro Weisz ◽  
Yukiko Kurashima ◽  
Kouichi Hashimoto ◽  
Tsutomu Ogura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Hypoxia Response Element ◽  
Response Element ◽  
Hypoxia Response ◽  
Hypoxia Inducible Factor 1 ◽  
Endothelial Growth Factor

Nitric oxide (NO) regulates production of vascular endothelial growth factor (VEGF) by normal and transformed cells. We demonstrate that NO donors may up-regulate the activity of the human VEGF promoter in normoxic human glioblastoma and hepatoma cells independent of a cyclic guanosine monophosphate–mediated pathway. Deletion and mutation analysis of the VEGF promoter indicates that the NO-responsive cis-elements are the hypoxia-inducible factor-1 (HIF-1) binding site and an adjacent ancillary sequence that is located immediately downstream within the hypoxia-response element (HRE). This work demonstrates that the HRE of this promoter is the primary target of NO. In addition, VEGF gene regulation by NO, as well as by hypoxia, is potentiated by the AP-1 element of the gene. Our study also reveals that NO and hypoxia induce an increase in HIF-1 binding activity and HIF-1 protein levels, both in the nucleus and the whole cell. These results suggest that there are common features of the NO and hypoxic pathways of VEGF induction, while in part, NO mediates gene transcription by a mechanism distinct from hypoxia. This is demonstrated by a difference in sensitivity to guanylate cyclase inhibitors and a different pattern of HIF-1 binding. These results show that there is a primary role for NO in the control of VEGF synthesis and in cell adaptations to hypoxia. (Blood. 2000;95:189-197)

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