Pharmaceuticals 2017, 10(2), 35; https://doi.org/10.3390/ph10020035
Modulation of TRP Channel Activity by Hydroxylation and Its Therapeutic Potential
1
School of Biological Sciences, University of Adelaide, Adelaide 5005, SA, Australia
2
School of Medicine, University of Adelaide, Adelaide 5005, SA, Australia
3
South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5005, SA, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Arpad Szallasi and Susan M. Huang
Received: 30 January 2017 / Revised: 15 March 2017 / Accepted: 24 March 2017 / Published: 27 March 2017
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
Abstract
Two transient receptor potential (TRP) channels—TRPA1 and TRPV3—are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their hydroxylation of the hypoxic inducible transcription factors (HIFs), mediating their hypoxic regulation. Consequently, these hydroxylases are currently being targeted therapeutically to modulate HIF activity in anemia, inflammation, and ischemic disease. Modulating the HIFs by targeting these hydroxylases may result in both desirable and undesirable effects on TRP channel activity, depending on the physiological context. For the best outcomes, these hydroxylases could be therapeutically targeted in pathologies where activation of both the HIFs and the relevant TRP channels are predicted to independently achieve positive outcomes, such as wound healing and obesity. View Full-Text
Figure 1
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Nagarajan, Y.; Rychkov, G.Y.; Peet, D.J. Modulation of TRP Channel Activity by Hydroxylation and Its Therapeutic Potential. Pharmaceuticals 2017, 10, 35.
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