Gating of the capsaicin receptor TRPV1 by UVA-light and oxidants are mediated by distinct mechanisms

Pantke, Sebastian; Leffler, Andreas; Eberhardt, Mirjam; Herzog, Christine; Leffler, Andreas

doi:10.1016/j.ceca.2021.102391

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Cryonotothenioids express high levels of antioxidants but still show evidence of high oxidation stress ( Todgham et al 2007 ; Chen et al 2008 ; Peck 2016 , O’Brien et al 2018 ). Several TRP channels are gated or modulated by ROS, including mammalian TRPV1, TRPA1, and TRPM7 ( Takahashi et al 2011 ; Inoue et al 2021 ; Pantke et al 2021 ). It has been hypothesized that aversive behavioral responses to heat are actually mediated by ROS gating of TRP channels ( Arenas et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Typically, redox sensitivity is modulated by methionine or cysteine residues, and methionines are overrepresented in the proteins of notothenioids ( Berthelot et al 2019 ). In TRPV1, cryonotothenioids and other teleosts lack two of the N-terminal cysteine residues important for oxidant-induced gating in mammalian channels, but do maintain one C-terminal cysteine shown to be important in redox sensitivity ( Chuang and Lin 2009 ; Pantke et al 2021 ). Notothenioid TRPA1b retains five out of ten cysteines that affect redox gating in mammalian channels, similar to other teleosts ( Takahashi et al 2011 ).…”

Section: Discussionmentioning

confidence: 99%

“…In TRPM7, both cysteines important for redox sensitivity in the human channel are conserved in cryonotothenioids, and we found significant diversifying selection at an additional cysteine substitution specific to cryonotothenioids ( Inoue et al 2021 ). As oxidants can potentiate heat-evoked responses via these residues, the loss or gain of cysteines may contribute to changing temperature gating in the presence of oxidants ( Pantke et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors

York

Zakon

2022

Genome Biology and Evolution

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Animals rely on their sensory systems to inform them of ecologically relevant environmental variation. In the Southern Ocean, the thermal environment has remained between -1.9 and 5 °C for 15 million years, yet we have no knowledge of how an Antarctic marine organism might sense their thermal habitat as we have yet to discover a thermosensitive ion channel that gates (opens/closes) below 10 °C. Here, we investigate the evolutionary dynamics of transient receptor potential (TRP) channels, which are the primary thermosensors in animals, within cryonotothenioid fishes—the dominant fish fauna of the Southern Ocean. We found cryonotothenioids have a similar complement of TRP channels as other teleosts (∼28 genes). Previous work has shown that thermosensitive-gating in a given channel is species specific, and multiple channels act together to sense the thermal environment. Therefore, we combined evidence of changes in selective pressure, gene gain/loss dynamics, and the first sensory ganglion transcriptome in this clade to identify the best candidate TRP channels that might have a functional dynamic range relevant for frigid Antarctic temperatures. We concluded that TRPV1a, TRPA1b, and TRPM4 are the likeliest putative thermosensors, and found evidence of diversifying selection at sites across these proteins. We also put forward hypotheses for molecular mechanisms of other cryonotothenioid adaptations, such as reduced skeletal calcium deposition, sensing oxidative stress, and unusual magnesium homeostasis. By completing a comprehensive and unbiased survey of these genes, we lay the groundwork for functional characterization and answering long-standing thermodynamic questions of thermosensitive gating and protein adaptation to low temperatures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors

York

Zakon

2022

Genome Biology and Evolution

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“…Only 0.8% of capsaicin-sensitive cells were hemin-sensitive in presence of DTT. The mutant construct hTRPV1-3C was previously demonstrated to lack redox sensitivity, but to have an intact sensitivity to UVA-light [ 27 , 28 ]. Accordingly, the magnitude of hemin-induced calcium influx was significantly reduced on hTRPV1-3C ( Figure 6 B,C, n = 273).…”

Section: Resultsmentioning

confidence: 99%

Distinct Mechanisms Account for In Vitro Activation and Sensitization of TRPV1 by the Porphyrin Hemin

Palmaers

Wiegand

Herzog

et al. 2021

IJMS

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TRPV1 mediates pain occurring during sickling episodes in sickle cell disease (SCD). We examined if hemin, a porphyrin released during intravascular hemolysis modulates TRPV1. Calcium imaging and patch clamp were employed to examine effects of hemin on mouse dorsal root ganglion (DRG) neurons and HEK293t cells expressing TRPV1 and TRPA1. Hemin induced a concentration-dependent calcium influx in DRG neurons which was abolished by the unspecific TRP-channel inhibitor ruthenium red. The selective TRPV1-inhibitor BCTC or genetic deletion of TRPV1 only marginally impaired hemin-induced calcium influx in DRG neurons. While hTRPV1 expressed in HEK293 cells mediated a hemin-induced calcium influx which was blocked by BCTC, patch clamp recordings only showed potentiated proton- and heat-evoked currents. This effect was abolished by the PKC-inhibitor chelerythrine chloride and in protein kinase C (PKC)-insensitive TRPV1-mutants. Hemin-induced calcium influx through TRPV1 was only partly PKC-sensitive, but it was abolished by the reducing agent dithiothreitol (DTT). In contrast, hemin-induced potentiation of inward currents was not reduced by DTT. Hemin also induced a redox-dependent calcium influx, but not inward currents on hTRPA1. Our data suggest that hemin induces a PKC-mediated sensitization of TRPV1. However, it also acts as a photosensitizer when exposed to UVA-light used for calcium imaging. The resulting activation of redox-sensitive ion channels such as TRPV1 and TRPA1 may be an in vitro artifact with limited physiological relevance.

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“…TRPV1 may be gated by a variety of physical and chemical stimuli, such as noxious heat (>42 °C), a decrease in extracellular pH, spider-derived vanillotoxins, agonists of plant origin (e.g., capsaicin), and fatty acids conjugated with amines (e.g., anandamide) [ 3 , 5 ]. Although not explicitly recognized as a sensor of endothelial redox signaling [ 60 ], TRPV1 may also be activated by oxidant stress ( Figure 3 ) [ 211 , 212 , 213 ], although the underlying mechanism varies among species. H 2 O 2 activates the rat TRPV1 by oxidizing the extracellular Cys621 ( Figure 3 ), which may serve as a switch to open the channel pore [ 211 ], whereas chicken TRPV1 is activated in a graded manner by the oxidation of multiple Cys residues that are located at the NH 2 and COOH termini [ 212 ].…”

Section: Ros Mediate Extracellular Ca 2+ Influx Through the Activation Of Transient Receptor Potential (Trp) Channelsmentioning

confidence: 99%

Reactive Oxygen Species and Endothelial Ca2+ Signaling: Brothers in Arms or Partners in Crime?

Negri¹,

Faris²,

Moccia³

2021

IJMS

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An increase in intracellular Ca2+ concentration ([Ca2+]i) controls virtually all endothelial cell functions and is, therefore, crucial to maintain cardiovascular homeostasis. An aberrant elevation in endothelial can indeed lead to severe cardiovascular disorders. Likewise, moderate amounts of reactive oxygen species (ROS) induce intracellular Ca2+ signals to regulate vascular functions, while excessive ROS production may exploit dysregulated Ca2+ dynamics to induce endothelial injury. Herein, we survey how ROS induce endothelial Ca2+ signals to regulate vascular functions and, vice versa, how aberrant ROS generation may exploit the Ca2+ handling machinery to promote endothelial dysfunction. ROS elicit endothelial Ca2+ signals by regulating inositol-1,4,5-trisphosphate receptors, sarco-endoplasmic reticulum Ca2+-ATPase 2B, two-pore channels, store-operated Ca2+ entry (SOCE), and multiple isoforms of transient receptor potential (TRP) channels. ROS-induced endothelial Ca2+ signals regulate endothelial permeability, angiogenesis, and generation of vasorelaxing mediators and can be exploited to induce therapeutic angiogenesis, rescue neurovascular coupling, and induce cancer regression. However, an increase in endothelial [Ca2+]i induced by aberrant ROS formation may result in endothelial dysfunction, inflammatory diseases, metabolic disorders, and pulmonary artery hypertension. This information could pave the way to design alternative treatments to interfere with the life-threatening interconnection between endothelial ROS and Ca2+ signaling under multiple pathological conditions.

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Gating of the capsaicin receptor TRPV1 by UVA-light and oxidants are mediated by distinct mechanisms

Cited by 8 publications

References 27 publications

Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors

Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors

Distinct Mechanisms Account for In Vitro Activation and Sensitization of TRPV1 by the Porphyrin Hemin

Reactive Oxygen Species and Endothelial Ca2+ Signaling: Brothers in Arms or Partners in Crime?

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