Related Experiment Video

Updated: Aug 25, 2026

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

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

Weiling Zhao1, Prabhat C Goswami, Mike E C Robbins

  • 1Department 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

Radiation Research
|March 25, 2004
PubMed

Insights

Radiation increases matrix metalloproteinase 2 (Mmp2) mRNA in kidney cells by stabilizing the mRNA and activating the ERK MAPK pathway. Antioxidants and MEK inhibitors block this radiation effect, suggesting a redox-mediated mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Radiation Biology

Background:

  • Matrix metalloproteinase 2 (Mmp2) protein levels increase in rat tubule epithelial cells (NRK52E) post-irradiation.
  • The underlying mechanisms for radiation-induced Mmp2 upregulation remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms behind radiation-induced Mmp2 upregulation in NRK52E cells.
  • To investigate the roles of mRNA stability, redox signaling, and the ERK MAPK pathway.

Main Methods:

  • NRK52E cells were irradiated with gamma rays (0-20 Gy).
  • Mmp2 mRNA levels were assessed over time.
  • Transcription inhibition (ActD), antioxidant treatment (N-acetylcysteine, ebselen), and MEK pathway inhibition (PD98059, U0126) were employed.
  • Reactive oxygen species (ROS) and Erk1/2 activation were analyzed.
  • Dominant-negative ERK mutant transfection was performed.

Main Results:

  • Irradiation caused time- and dose-dependent increases in Mmp2 mRNA.
  • Mmp2 mRNA stability increased in irradiated cells.
  • Antioxidants and MEK inhibitors prevented radiation-induced Mmp2 upregulation.
  • Irradiation induced ROS-mediated Erk1/2 activation, which was blocked by N-acetylcysteine.
  • Dominant-negative ERK abolished radiation-induced Erk phosphorylation and Mmp2 upregulation.

Conclusions:

  • Radiation upregulates Mmp2 mRNA partially through increased mRNA stability.
  • The process is redox-mediated and involves the ERK MAPK signaling pathway.

More Related Videos

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ10:05

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ

Published on: May 8, 2020

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...