TNF-α Increases Production of Reactive Oxygen Species through Cdk5 Activation in Nociceptive Neurons

Frontiers in Physiology
Rodrigo SandovalElias Utreras

Abstract

The participation of reactive oxygen species (ROS) generated by NOX1 and NOX2/NADPH oxidase has been documented during inflammatory pain. However, the molecular mechanism involved in their activation is not fully understood. We reported earlier a key role of Cyclin-dependent kinase 5 (Cdk5) during inflammatory pain. In particular, we demonstrated that TNF-α increased p35 expression, a Cdk5 activator, causing Cdk5-mediated TRPV1 phosphorylation followed by an increment in Ca2+ influx in nociceptive neurons and increased pain sensation. Here we evaluated if Cdk5 activation mediated by p35 transfection in HEK293 cells or by TNF-α treatment in primary culture of nociceptive neurons could increase ROS production. By immunofluorescence we detected the expression of catalytic subunit (Nox1 and Nox2) and their cytosolic regulators (NOXO1 and p47phox) of NOX1 and NOX2/NADPH oxidase complexes, and their co-localization with Cdk5/p35 in HEK293 cells and in nociceptive neurons. By using a hydrogen peroxide sensor, we detected a significant increase of ROS production in p35 transfected HEK293 cells as compared with control cells. This effect was significantly blocked by VAS2870 (NADPH oxidase inhibitor) or by roscovitine (Cdk5 activity inhi...Continue Reading

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Citations

Apr 23, 2019·Oral Diseases·Fuhua YangLu Zhang
Mar 11, 2020·Biomolecules·Piotr WójcikElżbieta Skrzydlewska
May 20, 2020·The Journal of Physiology·Wenly RuanJames Versalovic
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Jul 3, 2021·Antioxidants·Noemí Cárdenas-RodríguezBeatriz Hernández-Ochoa
Oct 10, 2021·Acta Neuropathologica Communications·Anusha JayaramanRichard Reynolds

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Methods Mentioned

BETA
confocal microscopy
biosensor

Software Mentioned

LSM Image Browser
ImageJ
GraphPad Prism

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