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1 April 2004 Radiation-Induced Up-regulation of Mmp2 Involves Increased mRNA Stability, Redox Modulation, and MAPK Activation
Weiling Zhao, Prabhat C. Goswami, Mike E. C. Robbins
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Abstract

Zhao, W., Goswami, P. C. and Robbins, M. E. C. Radiation- Induced Up-regulation of Mmp2 Involves Increased mRNA Stability, Redox Modulation, and MAPK Activation. Radiat. Res. 161, 418–429 (2004).

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 γ 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 t1/2 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.

Weiling Zhao, Prabhat C. Goswami, and Mike E. C. Robbins "Radiation-Induced Up-regulation of Mmp2 Involves Increased mRNA Stability, Redox Modulation, and MAPK Activation," Radiation Research 161(4), 418-429, (1 April 2004). https://doi.org/10.1667/3155
Received: 29 September 2003; Accepted: 1 December 2003; Published: 1 April 2004
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