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Vitamin C promotes human endothelial cell growth via the ERK-signaling pathway.

AbstractBACKGROUND:
Epidemiological, secondary prevention and small interventional trials suggest a preventive role of vitamin C for cardiovascular diseases (CAD), especially through improving endothelial dysfunction. Large primary prevention trials failed to confirm this. Mechanistic studies may contribute to resolve this discrepancy.
AIM OF THE STUDY:
We examined whether vitamin C activates mitogen-activated protein kinases (MAPK) in human umbilical cord venous endothelial cells (HUVECs) and whether reactive oxygen species (ROS) play a role in this process.
METHODS:
Subconfluent quiescent HUVECs were incubated with vitamin C alone or in combination with catalase (CAT) and/or hydrogenperoxide (H2O2). Intracellular MAPK were determined by Western blot, proliferation by cell count and DNA-synthesis by [3H]-thymidine-uptake.
RESULTS:
HUVECs were incubated with vitamin C (60 microM) for 5-60 min or for 20 min (30-90 microM). A dose-dependent phosphorylation of extracellular signal-regulated-kinases (ERKs)-1 and -2 with a maximum of phosphorylation at 15-20 min was observed and inhibitable by MEK1/2-inhibitor U0126 (5-10 microM). Vitamin C (60 microM) stimulated phosphorylation of ERK5, but not of p38 and c-Jun, demonstrating a different MAPK-activation pattern compared to H2O2. Vitamin C (60 microM) induced proliferation and a dose-dependent [3H]-thymidine-uptake (30-120 microM) within 20 h. CAT (0.3 U/ml) did neither suppress the vitamin C induced [3H]-thymidine-uptake nor ERK1/2-phosphorylation. CAT (0.3 U/ml), but not vitamin C (60 microM) abrogated the inhibitory effects of H2O2 (100 microM) on [3H]-thymidine-uptake.
CONCLUSION:
Physiological vitamin C-concentrations promote proliferation of subconfluent ECs by activating an ERK1/2 controlled pathway. Targeting MAPK by vitamin C may improve, besides antioxidant mechanisms, endothelial dysfunction by promoting a fast regeneration of the endothelium after tissue injury, particularly required during secondary prevention and early development.
AuthorsGudrun Ulrich-Merzenich, Heike Zeitler, Darius Panek, Dirk Bokemeyer, Hans Vetter
JournalEuropean journal of nutrition (Eur J Nutr) Vol. 46 Issue 2 Pg. 87-94 (Mar 2007) ISSN: 1436-6207 [Print] Germany
PMID17225921 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Butadienes
  • Enzyme Inhibitors
  • Nitriles
  • Reactive Oxygen Species
  • U 0126
  • DNA
  • Hydrogen Peroxide
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Ascorbic Acid
Topics
  • Antioxidants (pharmacology)
  • Ascorbic Acid (pharmacology)
  • Blotting, Western
  • Butadienes (pharmacology)
  • Cell Proliferation (drug effects)
  • DNA (biosynthesis)
  • Dose-Response Relationship, Drug
  • Endothelial Cells (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Humans
  • Hydrogen Peroxide (metabolism)
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Mitogen-Activated Protein Kinases (metabolism)
  • Nitriles (pharmacology)
  • Phosphorylation
  • Reactive Oxygen Species (metabolism)
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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