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Nox4- and Nox2-dependent oxidant production is required for VEGF-induced SERCA cysteine-674 S-glutathiolation and endothelial cell migration
| Content Provider | PubMed Central |
|---|---|
| Author | Evangelista, Alicia M. Thompson, Melissa D. Bolotina, Victoria M. Tong, Xiaoyong Cohen, Richard A. |
| Copyright Year | 2012 |
| Abstract | Endothelial cell (EC) migration in response to VEGF is a critical step in both physiological and pathological angiogenesis. Although VEGF signaling has been extensively studied, the mechanisms by which VEGF-dependent reactive oxygen species (ROS) production affects EC signaling are not well-understood. The aim of this study was to elucidate the involvement of Nox2- and Nox4-dependent ROS in VEGF-mediated EC Ca2+ regulation and migration. VEGF induced migration of human aortic EC into a scratch wound over 6 hours that was inhibited by overexpression of either catalase or SOD. EC stimulation by micromolar concentrations of H2O2 was inhibited by catalase, but also unexpectedly by SOD. Both VEGF and H2O2 increased S-glutathiolation of SERCA2b and increased Ca2+ influx into EC, and these events could be blocked by overexpression of catalase or overexpression of SERCA2b in which the reactive cysteine-674 was mutated to a serine. In determining the source of VEGF-mediated ROS production, our studies show that specific knock down of either Nox2 or Nox4 inhibited VEGF-induced S-glutathiolation of SERCA, Ca2+ influx, and EC migration. Treatment with H2O2 induced S-glutathiolation of SERCA and EC Ca2+ influx, overcoming the knockdown of Nox4, but not Nox2, and Amplex Red measurements indicated that Nox4 is the source of H2O2. These results demonstrate that VEGF stimulates EC migration through increased S-glutathiolation of SERCA and Ca2+ influx in a Nox4- and H2O2-dependent manner, requiring Nox2 downstream. |
| Related Links | http://dx.doi.org/10.1016/j.freeradbiomed.2012.10.546 |
| File Format | |
| ISSN | 08915849 |
| e-ISSN | 18734596 |
| Journal | Free radical biology & medicine |
| Issue Number | 12 |
| Volume Number | 53 |
| Language | English |
| Publisher Date | 2012-12-01 |
| Access Restriction | Open |
| Subject Keyword | Physiology (medical) Biochemistry Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology (medical) Biochemistry |
