Gene transfer of CuZn superoxide dismutase enhances the synthesis of vascular endothelial growth factor

Grzenkowicz-Wydra, Jolanta; Cisowski, Jaroslaw; Nakonieczna, Joanna; Zarębski, Adrian; Udilova, Natalia; Nohl, Hans; Józkowicz, Alicja; Podhajska, Anna J.; Dulak, Józef

doi:10.1023/b:mcbi.0000044386.45054.70

Cited by 34 publications

(23 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4). Thus, although Cu/ZnSOD and MnSOD have been considered as antioxidant enzymes in cytosol and mitochondria, respectively, they seem to serve as H 2 O 2 -generating, angiogenic enzymes in some settings [113]. These studies indicate that SOD treatment becomes anti-angiogenic and angiogenic depending on its isoform or location.…”

Section: Effects Of Superoxide Dismutase (Sod) On Angiogenesismentioning

confidence: 97%

“…By contrast, FGFinduced angiogenesis and tumor development are enhanced in Cu/ZnSOD transgenic mice [112] and gene transfer of Cu/ZnSOD in NIH3T3 fibroblasts enhances VEGF synthesis through an increase in H 2 O 2 [113]. Connor et al [114] have reported that overexpression of MnSOD promotes mitochondrial H 2 O 2 production, thereby stimulating EC sprouting and neovascularization in the CAM assay.…”

Section: Effects Of Superoxide Dismutase (Sod) On Angiogenesismentioning

confidence: 99%

See 1 more Smart Citation

Redox signaling in angiogenesis: Role of NADPH oxidase

Ushio‐Fukai

2006

Cardiovascular Research

429

310

View full text Add to dashboard Cite

Angiogenesis, a process of new blood vessel formation, is a key process involved in normal development and wound repair as well as in the various pathophysiologies such as ischemic heart and limb diseases and atherosclerosis. Reactive oxygen species (ROS) such as superoxide and H(2)O(2) function as signaling molecules in many aspects of growth factor-mediated responses including angiogenesis. Vascular endothelial growth factor (VEGF) is a key angiogenic growth factor and stimulates proliferation, migration, and tube formation of endothelial cells (ECs) primarily through the VEGF receptor type2 (VEGR2, KDR/Flk1). VEGF binding initiates autophosphorylation of VEGFR2, which results in activation of downstream signaling enzymes including ERK1/2, Akt, and eNOS in ECs, thereby stimulating angiogenesis. The major source of ROS in EC is a NADPH oxidase which consists of Nox1, Nox2 (gp91phox), Nox4, p22phox, p47phox, p67phox and the small G protein Rac1. The endothelial NADPH oxidase is activated by angiogenic factors including VEGF and angiopoietin-1. ROS derived from this enzyme stimulate diverse redox signaling pathways leading to angiogenesis-related gene induction as well as EC migration and proliferation, which may contribute to postnatal angiogenesis in vivo. The aim of this review is to provide an overview of the recent progress on the emerging area of the role of ROS derived from NADPH oxidase and redox signaling in angiogenesis. Understanding these mechanisms may provide insight into the NADPH oxidase and redox signaling components as potential therapeutic targets for treatment of angiogenesis-dependent cardiovascular diseases and for promoting angiogenesis in ischemic limb and heart diseases.

show abstract

Section: Effects Of Superoxide Dismutase (Sod) On Angiogenesismentioning

confidence: 97%

Section: Effects Of Superoxide Dismutase (Sod) On Angiogenesismentioning

confidence: 99%

Redox signaling in angiogenesis: Role of NADPH oxidase

Ushio‐Fukai

2006

Cardiovascular Research

429

310

View full text Add to dashboard Cite

show abstract

“…The expression of VEGF is regulated by HRE and the Sp1 responsive (Grzenkowicz-Wydra et al, 2004). It seems that the regulation of VEGF expression by either HRE or the Sp1 responsive element is copper-dependent, so that without HIF-1␣ accumulation, which acts through HRE, copper stimulates VEGF expression by affecting Sp1 regulation.…”

Section: Downloaded Frommentioning

confidence: 99%

Copper Is Required for Cobalt-Induced Transcriptional Activity of Hypoxia-Inducible Factor-1

Qiu

Ding²,

Zhang³

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Cobalt inhibits prolyl hydroxylases, leading to the accumulation of hypoxia-inducible factor-1␣ (HIF-1␣) and a concomitant increase in the transcriptional activity of HIF-1. Therefore, cobalt has been under development as a drug for activating HIF-1 under some disease conditions. However, it has been shown that ischemic conditions resulted in the loss of copper, and the activation of HIF-1 would not occur unless copper was supplemented. The present study was undertaken to test the hypothesis that copper is also required for the cobalt activation of HIF-1 transcriptional activity. Human umbilical vein endothelial cells subjected to treatment with cobalt chloride (CoCl 2 ) at concentrations above 25 M for 2 h resulted in an accumulation of HIF-1␣, which was determined by Western blot analysis, and an increase in the expression of vascular endothelial growth factor (VEGF), which was determined by real-time reverse transcription-polymerase chain reaction analysis for mRNA levels and enzyme-linked immunosorbent assay analysis for protein levels. The copper chelator tetraethylenepentamine at 25 M did not significantly affect the accumulation of HIF-1␣ but blocked increases in VEGF mRNA and protein levels, an effect that could be reversed by the addition of 25 M copper sulfate (CuSO 4 ). In addition, gene silencing of the copper chaperone for Cu,Zn-superoxide dismutase blocked VEGF expression with little effect on cobalt-induced HIF-1␣ accumulation. The present study thus demonstrates that copper was required for cobalt-activated transcriptional activity of HIF-1, although copper did not affect cobalt-induced accumulation of HIF-1␣ in the cells.

show abstract

“…Consistent with SOD3 2/2 mice, SOD1-deficient mice show impaired neovascularization, as assessed by reduction of blood flow recovery and capillary density in ischemic muscle (80). Overexpression of human SOD1 in mouse NIH 3T3 fibroblasts increased SOD activity, enhanced intracellular generation of H 2 O 2 , and significantly stimulated VEGF production (81). FGF-induced angiogenesis and tumor development are enhanced in SOD1 transgenic mice (150).…”

mentioning

confidence: 93%

Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases

Fukai

Ushio‐Fukai

2011

Antioxidants & Redox Signaling

1,604

1,099

View full text Add to dashboard Cite

Excessive reactive oxygen species Revised abstract, especially superoxide anion (O 2 -), play important roles in the pathogenesis of many cardiovascular diseases, including hypertension and atherosclerosis. Superoxide dismutases (SODs) are the major antioxidant defense systems against O 2 -, which consist of three isoforms of SOD in mammals: the cytoplasmic Cu/ZnSOD (SOD1), the mitochondrial MnSOD (SOD2), and the extracellular Cu/ZnSOD (SOD3), all of which require catalytic metal (Cu or Mn) for their activation. Recent evidence suggests that in each subcellular location, SODs catalyze the conversion of O 2 -H 2 O 2 , which may participate in cell signaling. In addition, SODs play a critical role in inhibiting oxidative inactivation of nitric oxide, thereby preventing peroxynitrite formation and endothelial and mitochondrial dysfunction. The importance of each SOD isoform is further illustrated by studies from the use of genetically altered mice and viral-mediated gene transfer. Given the essential role of SODs in cardiovascular disease, the concept of antioxidant therapies, that is, reinforcement of endogenous antioxidant defenses to more effectively protect against oxidative stress, is of substantial interest. However, the clinical evidence remains controversial. In this review, we will update the role of each SOD in vascular biologies, physiologies, and pathophysiologies such as atherosclerosis, hypertension, and angiogenesis. Because of the importance of metal cofactors in the activity of SODs, we will also discuss how each SOD obtains catalytic metal in the active sites. Finally, we will discuss the development of future SODdependent therapeutic strategies. Antioxid. Redox Signal. 15, 1583-1606.

show abstract

Gene transfer of CuZn superoxide dismutase enhances the synthesis of vascular endothelial growth factor

Cited by 34 publications

References 81 publications

Redox signaling in angiogenesis: Role of NADPH oxidase

Redox signaling in angiogenesis: Role of NADPH oxidase

Copper Is Required for Cobalt-Induced Transcriptional Activity of Hypoxia-Inducible Factor-1

Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases

Contact Info

Product

Resources

About