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October 13, 1995Science2,528 citations

Requirement for Generation of H 2 O 2 for Platelet-Derived Growth Factor Signal Transduction

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MSMaitrayee SundaresanZYZu-Xi YuVFVictor J. Ferrans

Key Points

  • To determine whether hydrogen peroxide is generated during platelet-derived growth factor (PDGF) stimulation and functions as an obligatory signal-transducing messenger in vascular smooth muscle cells.
  • Stimulated cultured rat vascular smooth muscle cells (VSMCs) with platelet-derived growth factor (PDGF).
  • Suppressed intracellular hydrogen peroxide (H2O2) levels using either the antioxidant enzyme catalase or the chemical antioxidant N-acetylcysteine.
  • Evaluated downstream cellular responses including protein tyrosine phosphorylation, mitogen-activated protein (MAP) kinase activation, DNA synthesis, and chemotaxis.
  • PDGF stimulation induced a transient increase in intracellular H2O2 concentration in rat VSMCs, which was blunted by catalase or N-acetylcysteine.
  • Inhibition of the PDGF-induced H2O2 increase suppressed downstream tyrosine phosphorylation, MAP kinase activation, DNA synthesis, and cellular chemotaxis.

Abstract

Stimulation of rat vascular smooth muscle cells (VSMCs) by platelet-derived growth factor (PDGF) transiently increased the intracellular concentration of hydrogen peroxide (H2O2). This increase could be blunted by increasing the intracellular concentration of the scavenging enzyme catalase or by the chemical antioxidant N-acetylcysteine. The response of VSMCs to PDGF, which includes tyrosine phosphorylation, mitogen-activated protein kinase stimulation, DNA synthesis, and chemotaxis, was inhibited when the growth factor-stimulated rise in H2O2 concentration was blocked. These results suggest that H2O2 may act as a signal-transducing molecule, and they suggest a potential mechanism for the cardioprotective effects of antioxidants.

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Cite This Study

Sundaresan et al. (1995) studied this question.

synapsesocial.com/papers/6a009f496018b8d0892dc5cfhttps://doi.org/10.1126/science.270.5234.296
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