Radiation-induced up-regulation of Mmp2 involves increased mRNA stability, redox modulation, and MAPK activation

Weiling Zhao; Prabhat C Goswami; Mike E C Robbins

doi:10.1667/3155

Back

Radiation-induced up-regulation of Mmp2 involves increased mRNA stability, redox modulation, and MAPK activation

Journal article

Peer reviewed

Radiation-induced up-regulation of Mmp2 involves increased mRNA stability, redox modulation, and MAPK activation

Weiling Zhao, Prabhat C Goswami and Mike E C Robbins

Radiation research, Vol.161(4), pp.418-429

04/2004

DOI: 10.1667/3155

PMID: 15038770

View Online

Abstract

We have previously observed time- and dose-dependent increases in matrix metalloproteinase 2 (Mmp2) protein levels in rat tubule epithelial cells (NRK52E) after irradiation. However, the mechanism(s) involved remains unclear. In the present study, irradiating NRK52E cells with 0-20 Gy gamma rays was associated with time- and dose-dependent increases in Mmp2 mRNA. Studies using the transcription inhibitor actinomycin D (ActD) added 24 h after irradiation revealed the t(1/2) of Mmp2 mRNA to be approximately 8 h in control cells. In contrast, the increase in Mmp2 mRNA levels in irradiated cells was essentially unchanged after incubation with ActD for up to 12 h. Incubating cells with the antioxidants N-acetylcysteine or ebselen or the MEK pathway inhibitors PD98059 and U0126 prior to irradiation abolished the radiation-induced up-regulation of Mmp2. Irradiating NRK52E cells led to reactive oxygen species-mediated Erk1/2 activation; preincubation with NAC prevented the radiation-induced increase in phosphorylated Erk1/2. Transfecting cells with a dominant-negative ERK mutant completely inhibited radiation-induced Erk phosphorylation and abolished the radiation-induced up-regulation of Mmp2 protein. Thus the radiation-induced up-regulation of Mmp2 mRNA is due in part to increased mRNA stability and is mediated by redox; the ERK MAPK signaling pathway may be involved.

Up-Regulation

Phosphorylation

Epithelial Cells - metabolism

Nitriles - pharmacology

Oxidative Stress

RNA, Messenger - radiation effects

MAP Kinase Signaling System

Transfection

Genes, Dominant

Time Factors

Puromycin - pharmacology

Flavonoids - pharmacology

Matrix Metalloproteinase 2 - biosynthesis

Cell Line

Butadienes - pharmacology

Oxidation-Reduction

Signal Transduction

Cells, Cultured

Enzyme Inhibitors - pharmacology

Rats

Antioxidants - pharmacology

RNA - chemistry

Blotting, Western

Kidney Tubules - cytology

Blotting, Northern

Animals

Enzyme Activation

Kinetics

Mutation

DNA, Complementary - metabolism

Dactinomycin - pharmacology

Dose-Response Relationship, Radiation

Mitogen-Activated Protein Kinase 3

Mitogen-Activated Protein Kinase 1 - metabolism

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: Radiation-induced up-regulation of Mmp2 involves increased mRNA stability, redox modulation, and MAPK activation
Creators: Weiling Zhao - Department of Radiation Oncology, Brain Tumor Center of Wake Forest University, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. wzhao@wfubmc.edu
Prabhat C Goswami
Mike E C Robbins
Resource Type: Journal article
Publication Details: Radiation research, Vol.161(4), pp.418-429
Publisher: United States
DOI: 10.1667/3155
PMID: 15038770
ISSN: 0033-7587
eISSN: 1938-5404
Grant note: DK51612 / NIDDK NIH HHS
Language: English
Date published: 04/2004
Academic Unit: Radiation Oncology
Record Identifier: 9984047719902771

Metrics

9 Record Views

20 Times Cited - Web of Science