Nox2 and Nox4 mediate tumour necrosis factor-α-induced ventricular remodelling in mice.
Bottom Line: ROS was significantly decreased by inhibitors of NADPH oxidase, but not by inhibitors of other ROS production systems.Nox2 and Nox4 siRNA significantly attenuated TNF-α-induced ROS and upregulation of IL-1β and IL-6 in cardiomyocytes.Our study highlights a novel TNF-α-induced chronic ventricular remodelling mechanism mediated by sequential regulation of Nox2 and Nox4 subunits.
Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. email@example.comShow MeSH
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Mentions: To detect ROS in the ex vivo ventricular tissues of TNF-α-injected and control mice, DHE staining was performed. No significant difference in fluorescent intensity was observed among day-1 TNF-α-injected and control mice (Fig. 1A and B). However, the fluorescent intensities of mice injected with TNF-α 7 and 28 days previously were significantly higher than control mice. Mitochondrial ROS in the ex vivo ventricular tissues of TNF-α-injected and control mice showed slight fluorescence intensity (Fig. 1C). However, there was no significant difference between TNF-α injected and control mice at all three time points (Fig. 1D). The ROS in the ventricular homogenates was assessed by CM-H2DCFDA fluorescence assay. Mice injected with TNF-α 7 and 28 days previously showed a significant increase in fluorescence compared to the controls, but not in the mice injected 1 day previously (Fig. 1E). The enzymatic sources of the ROS were examined using specific inhibitors in the fluorescence assay. ROS production was significantly reduced with SOD and abolished by NADPH oxidase inhibitors, DPI and apocynin. However, allopurinol, L-NAME and rotenone had no effect on TNF-α-induced ROS in the ventricles (Fig. 1F).
Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. firstname.lastname@example.org