Role of reactive oxygen species in bradykinin-induced mitogen-activated protein kinase and c-fos induction in vascular cells

Eddie L. Greene, Victoria Velarde, Ayad A. Jaffa

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Bradykinin stimulates proliferation of aortic vascular smooth muscle cells (VSMCs). We investigated the action of bradykinin on the phosphorylation state of the mitogen-activated protein kinases p42(mapk) and p44(mapk) in VSMCs and tested the hypothesis that reactive oxygen species (ROS) might be involved in the signal transduction pathway linking bradykinin activation of nuclear transcription factors to the phosphorylation of p42(mapk) and p44(mapk) Bradykinin (10-8 mol/L) rapidly increased (4- to 5- fold) the phosphorylation of p42(mapk) and p44(mapk) in VSMCs. Preincubation of VSMCs with either N-acetyl-L-cysteine and/or α-lipoic acid significantly decreased bradykinin-induced cytosolic and nuclear phosphorylation of p42(mapk) and p44(mapk). In addition, the induction c-fos mRNA levels by bradykinin was completely abolished by N-acetyl-L-cysteine and α-lipoic acid. Using the cell-permeable fluorescent dye dichlorofluorescein diacetate, we determined that bradykinin (10-8 mol/L) rapidly increased the generation of ROS in VSMCs. The NADPH oxidase inhibitor diphenylene iodonium (DPI) blocked bradykinin-induced c-fos mRNA expression and p42(mapk) and p44(mapk) activation, implicating NADPH oxidase as the source for the generation of ROS. These findings demonstrate that the phosphorylation of cytosolic and nuclear p42(mapk) and p44(mapk) and the expression of c-fos mRNA in VSMCs in response to bradykinin are mediated via the generation of ROS and implicate ROS as important mediators in the signal transduction pathway through which bradykinin promotes VSMC proliferation in states of vascular injury.

Original languageEnglish (US)
Pages (from-to)942-947
Number of pages6
JournalHypertension
Volume35
Issue number4
DOIs
StatePublished - Apr 2000

Keywords

  • Bradykinin
  • Kinases
  • Proto-oncogenes
  • Reactive oxygen species

ASJC Scopus subject areas

  • Internal Medicine

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