onsdag den 6. marts 2013

TRPA1, Hypoxia and ME?

David S. Bell has written the book: “Cellular Hypoxia and Neuro-Immune Fatigue”. http://www.davidsbell.com/DSBBooks.htm

So, hypoxia and neuro-immune fatigue have already been linked together. I will not go further into that subject, but I will give you a few good quotes and links to the connection between TRPA1 and hypoxia:

“Monitoring oxygen (O2) levels is essential to optimizing aerobic metabolism and ensuring proper biological processes in most eukaryotes. The spice chemosensor TRPA1 is a previously unidentified O2 sensor in the mammalian sensory nervous system that warns against hyperoxia and hypoxia.”
Reference: Channels: A TR(i)P in the air
http://www.nature.com/nchembio/journal/v7/n10/full/nchembio.669.html

“Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O(2), it is critical to elucidate the molecular mechanisms responsible for O(2) sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O(2). O(2) sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O(2)-dependent inhibition on TRPA1 activity in normoxia, direct O(2) action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O(2)-sensing mechanism mediated by TRPA1.”
Reference: TRPA1 underlies a sensing mechanism for O2
http://www.ncbi.nlm.nih.gov/pubmed/21873995

“…Recent studies have revealed that changes in the availability of molecular oxygen (O2) also control the activation of TRP channels. Anoxia induced by O2-glucose deprivation and severe hypoxia (1% O2) activates TRPM7 and TRPC6, respectively, whereas TRPA1 has recently been identified as a novel sensor of hyperoxia and mild hypoxia (15% O2) in vagal and sensory neurons. TRPA1 also detects other gaseous molecules such as hydrogen sulfide (H2S) and carbon dioxide (CO2). In this review, we focus on how signaling by gaseous molecules is sensed and integrated by TRP channels.”
Reference: TRP channels: sensors and transducers of gasotransmitter signals
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429092/

“In human fibroblast-like synoviocytes, key inflammatory mediators (tumor necrosis factor-α and interleukin-1α) induced TRPA1 gene expression via nuclear factor-κB signaling and downstream activation of the transcription factor hypoxia-inducible factor-1α (HIF1α). HIF1α unexpectedly acted by binding to a specific hypoxia response element-like motif and its flanking regions in the TRPA1 gene. The induced TRPA1 channels, which were intrinsically activated by endogenous hydrogen peroxide and Zn(2+), suppressed secretion of interleukin-6 and interleukin-8. The data suggest a previously unrecognized HIF1α mechanism that links inflammatory mediators to ion channel expression.”
Reference: Hypoxia-inducible factor-1α (HIF1α) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release.
http://www.ncbi.nlm.nih.gov/pubmed/22843691

“We concluded that acute intermittent hypoxia (AIH) sensitizes lung vagal C fibers (LVCFs) in rats, thus resulting in exaggerated airway reflexogenic responses to chemical stimulants, possibly by ROS action and activation of TRPA1 receptors.”
Reference: Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1
http://www.ncbi.nlm.nih.gov/pubmed/23076873

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