Erk1/2 and Elk1 Are Involved in PKCα-Induced Nox4 Expression in Human Endothelial Cells

Authors

  • Solveig Hasselwander Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany
  • Frank Schlufter Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany
  • Ning Xia Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany
  • Huige Li Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany

Keywords:

Elk1; Erk1/2; Gene expression; NADPH oxidase; Nox4; Protein kinase C

Abstract

In a previous study, we have shown that activation of protein kinase C-alpha (PKCα) leads to an upregulation of Nox4 expression in human endothelial cells. The present study was conducted to analyze the signaling pathway linking PKCα activation to Nox4 upregulation. Treatment of human EA.hy 926 endothelial cells with phorbol 12-myristate 13-acetate (PMA) increased Nox4 expression, which was prevented by the PKC inhibitor Gö 6983 and by siRNA-mediated knock-down of PKCα. PKC activation is known to stimulate the Ras/Raf/MEK/Erk/Elk1 pathway. Indeed, PMA treatment of EA.hy 926 cells induced Erk1/2 phosphorylation and Elk1 upregulation. The PMA-induced Nox4 expression in EA.hy 926 cells could be prevented by the MEK1 inhibitor PD98059 and by siRNA-mediated knock-down of Erk1/2 or Elk1, indicating a dependency of Nox4 expression on Erk1/2 and Elk1. In promoter activity analyses, PMA treatment of EA.hy 926 cells increased the activity of the Nox4 promoter fragments of 2160 bp and 672 bp in length, but not that of 495 bp. Consistently, a potential Elk1 binding site was found between –644 bp and –629 bp in the Nox4 promotor by in silico analysis. In conclusion, Erk1/2 and Elk1 are involved in the signaling pathway linking PKCα activation to Nox4 expression.

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Published

2019-11-01

How to Cite

Hasselwander, S., Schlufter, F., Xia, N., & Li, H. (2019). Erk1/2 and Elk1 Are Involved in PKCα-Induced Nox4 Expression in Human Endothelial Cells. Reactive Oxygen Species, 8(24), 323–331. Retrieved from https://rosj.org/index.php/ros/article/view/246

Issue

Section

ORIGINAL RESEARCH