Abstract
We examined whether steady-state mRNA levels of five tumor suppressor genes are subjected to oxidative stress. Superoxide radical-generating menadione and serum deprivation diminished the steady-state mRNA levels for the genes phosphatase and tensin homolog (PTEN), ubiquitin specific peptidase 28 (USP28), damage-regulated autophagy modulator (DRAM), TP53-induced glycolysis and apoptosis regulator (TIGAR), and cylindromatosis (CYLD). Hydrogen peroxide showed suppression in steady-state mRNA levels for USP28, DRAM, TIGAR, and CYLD but not for PTEN. The steady-state mRNA levels specific for all five genes were enhanced by antioxidants, such as glutathione and N-acetylcysteine. The HepG2 stable transfectants overexpressing the mitochondrial isoform of human glutaredoxin, Grx2a, and containing a relatively low reactive oxygen species (ROS) level were assessed to contain the increased steady-state mRNA levels specific for the five tumor suppressor genes. In brief, the steady-state mRNA levels specific for these genes are negatively regulated by oxidative stress through the mediation of ROS.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antioxidants / metabolism
-
Apoptosis Regulatory Proteins
-
Deubiquitinating Enzyme CYLD
-
Down-Regulation
-
Gene Expression
-
Genes, Tumor Suppressor*
-
Glutaredoxins / genetics
-
Hep G2 Cells
-
Humans
-
Intracellular Signaling Peptides and Proteins / genetics*
-
Intracellular Signaling Peptides and Proteins / metabolism
-
Membrane Proteins / genetics*
-
Membrane Proteins / metabolism
-
Mitochondria / genetics
-
Mitochondria / metabolism
-
Oxidative Stress / genetics*
-
PTEN Phosphohydrolase / genetics*
-
PTEN Phosphohydrolase / metabolism
-
Phosphoric Monoester Hydrolases
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Reactive Oxygen Species / metabolism
-
Superoxides / metabolism
-
Tumor Cells, Cultured
-
Tumor Suppressor Proteins / genetics*
-
Tumor Suppressor Proteins / metabolism
-
Ubiquitin Thiolesterase / genetics*
-
Ubiquitin Thiolesterase / metabolism
Substances
-
Antioxidants
-
Apoptosis Regulatory Proteins
-
DRAM1 protein, human
-
Glutaredoxins
-
Intracellular Signaling Peptides and Proteins
-
Membrane Proteins
-
RNA, Messenger
-
Reactive Oxygen Species
-
Tumor Suppressor Proteins
-
USP28 protein, human
-
Superoxides
-
Phosphoric Monoester Hydrolases
-
TIGAR protein, human
-
PTEN Phosphohydrolase
-
PTEN protein, human
-
CYLD protein, human
-
Deubiquitinating Enzyme CYLD
-
Ubiquitin Thiolesterase