TRPs as Chemosensors (ROS, RNS, RCS, Gasotransmitters)

Abstract

The transient receptor potential (trp) gene superfamily encodes TRP proteins that act as multimodal sensor cation channels for a wide variety of stimuli from outside and inside the cell. Upon chemical or physical stimulation of cells, TRP channels transduce electrical and/or Ca(2+) signals via their cation channel activities. These functional features of TRP channels allow the body to react and adapt to different forms of environmental changes. Indeed, members of one class of TRP channels have emerged as sensors of reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive carbonyl species (RCS), and gaseous messenger molecules including molecular oxygen (O2), hydrogen sulfide (H2S), and carbon dioxide (CO2). Hydrogen peroxide (H2O2), an ROS, triggers the production of ADP-ribose, which binds and activates TRPM2. In addition to TRPM2, TRPC5, TRPV1, and TRPA1 are also activated by H2O2 via modification of cysteine (Cys) free sulfhydryl groups. Nitric oxide (NO), a vasoactive gaseous molecule, regulates TRP channels directly via Cys S-nitrosylation or indirectly via cyclic GMP (cGMP)/protein kinase G (PKG)-dependent phosphorylation. Anoxia induced by O2-glucose deprivation and severe hypoxia activates TRPM7 and TRPC6, respectively, whereas TRPA1 serves as a sensor of mild hypoxia and hyperoxia in vagal and sensory neurons. TRPA1 also detects other gaseous molecules, such as hydrogen sulfide (H2S) and carbon dioxide (CO2). In this review, we highlight our current knowledge of TRP channels as chemosensors for ROS, RNS, RCS, and gaseous molecules and discuss their functional impacts on physiological and pathological events.

The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels

“…Melastatin and vanilloid subfamilies include TRP melastatin 2 (TRPM2) and TRP vanilloid 1 (TRPV1) Ca 2+ permeable cation channels49. Capsaicin (CAP) is a pungent component of hot chili peppers, and TRPV1 is activated by different stimuli, including CAP 10 and oxidative stress11. A growing amount of evidence has shown that ADPR is produced as a byproduct of NAD metabolism.…”

RhoA/Rho-Kinase in the Cardiovascular System

“…NO regulates TRP channels via cGMP/PKG-dependent phosphorylation. 119 Excessive ROS target multiple biomolecules, causing numerous cellular complications, including lipid peroxidation, protein oxidation/inactivation, and DNA damage/mutations. 117 Furthermore, increased O 2 − levels attenuate endothelium-dependent relaxation and enhance VSMC contraction through the formation of hydroxyl radicals.…”

α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

“…Further studies have pointed out that reactive oxygen species (ROS) and reactive nitrogen species may change activities of voltage-gated Na + , Ca 2+ , and K + channels in the aging process 16. ROS and reactive nitrogen species also activated and potentiated the TRPV1 and TRPM2 cation channels 17,18. Whether oxidative stress is involved in the modulation of NaV1.7 and NaV1.8 activities under diabetic conditions is not known.…”