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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Cell transformation by the superoxide-generating oxidase Mox1
Y A Suh1, R S Arnold, B Lassegue
1Department of Biochemistry, Emory University Medical School, Atlanta, Georgia 30322, USA.
Abstract:
Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer. Many cancer cells show increased production of ROS, and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation and express growth-related genes. ROS are generated in response to growth factors, and may affect cell growth, for example in vascular smooth-muscle cells. Increased ROS in Ras-transformed fibroblasts correlates with increased mitogenic rate. Here we describe the cloning of mox1, which encodes a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase of phagocytes, gp91phox. mox1 messenger RNA is expressed in colon, prostate, uterus and vascular smooth muscle, but not in peripheral blood leukocytes. In smooth-muscle cells, platelet-derived growth factor induces mox1 mRNA production, while antisense mox1 mRNA decreases superoxide generation and serum-stimulated growth. Overexpression of mox1 in NIH3T3 cells increases superoxide generation and cell growth. Cells expressing mox1 have a transformed appearance, show anchorage-independent growth and produce tumours in athymic mice. These data link ROS production by Mox1 to growth control in non-phagocytic cells.
Insights
Reactive oxygen species (ROS) are linked to cancer and cell growth. A newly identified gene, mox1, produces ROS in non-phagocytic cells, driving cell proliferation and tumor formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Reactive oxygen species (ROS) play a role in mitogenic signaling and cancer development.
- Increased ROS production is observed in many cancer cells, correlating with enhanced proliferation.
Purpose of the Study:
- To identify and characterize a novel gene involved in ROS production in non-phagocytic cells.
- To investigate the role of this gene in cell growth, proliferation, and tumor formation.
Main Methods:
- Cloning of the mox1 gene, a homolog of gp91phox.
- Analysis of mox1 mRNA expression in various tissues.
- Investigating the effects of mox1 manipulation (antisense, overexpression) on ROS generation and cell growth in vitro.
- Assessing tumor formation in vivo using athymic mice.
Main Results:
- mox1 encodes a superoxide-generating NADPH oxidase homolog and is expressed in colon, prostate, uterus, and vascular smooth muscle.
- Platelet-derived growth factor induces mox1 mRNA in smooth muscle cells.
- Antisense mox1 reduced superoxide generation and growth; mox1 overexpression increased superoxide generation and cell growth.
- mox1-expressing cells exhibited a transformed phenotype, anchorage-independent growth, and formed tumors in mice.
Conclusions:
- The mox1 gene links ROS production to growth control in non-phagocytic cells.
- mox1 is a key regulator of cell proliferation and exhibits oncogenic potential.
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