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Nox4 is a major source of superoxide production in human brain pericytes.
- Source :
-
Journal of vascular research [J Vasc Res] 2014; Vol. 51 (6), pp. 429-38. Date of Electronic Publication: 2015 Jan 22. - Publication Year :
- 2014
-
Abstract
- Background: Pericytes are multifunctional cells surrounding capillaries and postcapillary venules. In brain microvasculature, pericytes play a pivotal role under physiological and pathological conditions by producing reactive oxygen species (ROS). The aims of this study were to elucidate the source of ROS and its regulation in human brain pericytes.<br />Methods: The expression of Nox enzymes in the cells was evaluated using RT-PCR and western blot. Superoxide production was determined by superoxide dismutase-inhibitable chemiluminescence. Silencing of Nox4 was performed using RNAi, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay.<br />Results: Nox4 was predominant among the Nox family in human brain pericytes. Membrane fractions of cells produced superoxide in the presence of NAD(P)H. Superoxide production was almost abolished with diphenileneiodonium, a Nox inhibitor; however, inhibitors of other possible superoxide-producing enzymes had no effect on NAD(P)H-dependent superoxide production. Pericytes expressed angiotensin II (Ang II) receptors, and Ang II upregulated Nox4 expression. Hypoxic conditions also increased the Nox4 expression. Silencing of Nox4 significantly reduced ROS production and attenuated cell proliferation.<br />Conclusion: Our study showed that Nox4 is a major superoxide-producing enzyme and that its expression is regulated by Ang II and hypoxic stress in human brain pericytes. In addition, Nox4 may promote cell growth.<br /> (© 2015 S. Karger AG, Basel.)
- Subjects :
- Angiotensin II metabolism
Animals
Cell Hypoxia
Cell Membrane enzymology
Cell Proliferation
Cells, Cultured
Disease Models, Animal
Enzyme Inhibitors pharmacology
Humans
Infarction, Middle Cerebral Artery enzymology
Male
Mice
Microvessels enzymology
NADPH Oxidase 4
NADPH Oxidases antagonists & inhibitors
NADPH Oxidases genetics
Pericytes drug effects
RNA Interference
Receptors, Angiotensin metabolism
Time Factors
Transfection
Brain blood supply
NADPH Oxidases metabolism
Pericytes enzymology
Superoxides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0135
- Volume :
- 51
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of vascular research
- Publication Type :
- Academic Journal
- Accession number :
- 25612841
- Full Text :
- https://doi.org/10.1159/000369930