Reactive oxygen species stimulate VEGF production from C2C12 skeletal myotubes through a PI3K/Akt pathway

Ioanna Kosmidou, Angeliki Xagorari, Charis Roussos, Andreas Papapetropoulos

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulus, the expression of which increases in skeletal muscle after exercise. Because exercise is also accompanied by increased intramuscular reactive oxygen species (ROS) generation, we tested the hypothesis that ROS stimulate VEGF production from skeletal myotubes. Differentiated C2C12 skeletal myotubes exposed to ROS-producing agents exhibited a concentration-dependent increase in VEGF production, whereas undifferentiated myoblasts did not respond to oxidants. Moreover, conditioned medium from ROS-treated myotubes increased the bovine lung microvascular cell proliferation rate. To study the mechanism(s) involved in the stimulation of VEGF production by ROS, myotubes were pretreated with a selective phosphatidylinositol 3-kinase (PI3K) inhibitor, LY-294002, before being exposed to hydrogen peroxide or pyrogallol. LY-294002 attenuated both Akt phosphorylation and VEGF production. In addition, oxidants increased nuclear factor-κB-dependent promoter activity in transiently transfected myotubes; however, pretreatment with the pharmacological inhibitor of nuclear factor-κB, diethyldithiocarbamate, did not affect the oxidant-stimulated VEGF release. We conclude that ROS induce VEGF release from myotubes via a PI3K/Akt-dependent pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Volume280
Issue number4 PART 1
StatePublished - Apr 1 2001
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Skeletal Muscle Fibers
Vascular Endothelial Growth Factor A
Reactive Oxygen Species
Oxidants
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Pyrogallol
Ditiocarb
Myoblasts
Conditioned Culture Medium
Hydrogen Peroxide
Skeletal Muscle
Phosphorylation
Cell Proliferation
Pharmacology
Lung

Keywords

  • Exercise
  • Phosphatidylinositol 3-kinase
  • Protein kinase B
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Reactive oxygen species stimulate VEGF production from C2C12 skeletal myotubes through a PI3K/Akt pathway. / Kosmidou, Ioanna; Xagorari, Angeliki; Roussos, Charis; Papapetropoulos, Andreas.

In: American Journal of Physiology, Vol. 280, No. 4 PART 1, 01.04.2001.

Research output: Contribution to journalArticle

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