Advances in modulating thermosensory TRP channels

Ferrer‐Montiel, Antonio; Fernández-Carvajal, Asia; Planells-Cases, Rosa; Fernández‐Ballester, Gregorio; González-Ros, José M.; Messeguer, Àngel; González‐Muñiz, Rosario

doi:10.1517/13543776.2012.711320

Cited by 83 publications

(77 citation statements)

References 97 publications

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“…In addition to this complexity, the function of these channels is critically regulated by the formation of signaling complexes (known as signalplexes) with a variety of accessory and/or signaling proteins [25][26][27][28][29]. Recent and promising findings suggest that manipulation of these interactions between TRP channels and their regulatory proteins can be exploited for therapeutic intervention [30].…”

Section: Introductionmentioning

confidence: 99%

Lipids as central modulators of sensory TRP channels

Ciardo

Ferrer-Montiel

2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane. This lipid-based modulatory effect is being considered an alternative and promising approach to regulate TRP channel dysfunction in diseases. Here, we review the current progress in this exciting field highlighting a complex channel regulation by a large diversity of lipid molecules and suggesting some diseases that may benefit from a membrane lipid therapy. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

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Section: Introductionmentioning

confidence: 99%

Lipids as central modulators of sensory TRP channels

Ciardo

Ferrer-Montiel

2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…TRP channels mainly differ in their cytosolic N-and C-terminal domains, which are involved in channel gating and mediating intracellular signaling. Indeed, most of TRP channels, if not all, are part of protein complexes known as signalplexes [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

TRP channels interaction with lipids and its implications in disease

Taberner

Fernández‐Ballester

Fernández-Carvajal

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Transient receptor potential (TRP) proteins are a family of ion channels central for sensory signaling. These receptors and, in particular, those involved in thermal sensing are also involved in pain signaling. Noteworthy, thermosensory receptors are polymodal ion channels that respond to both physical and chemical stimuli, thus integrating different environmental clues. In addition, their activity is modulated by algesic agents and lipidergic substances that are primarily released in pathological states. Lipids and lipid-like molecules have been found that can directly activate some thermosensory channels or modulate their activity by either potentiating or inhibiting it. To date, more than 50 endogenous lipids that can regulate TRP channel activity in sensory neurons have been described, thus representing the majority of known endogenous TRP channel modulators. Lipid modulators of TRP channels comprise lipids from a variety of metabolic pathways, including metabolites of the cyclooxygenase, lipoxygenase and cytochrome-P450 pathways, phospholipids and lysophospholipids. Therefore, TRP-channels are able to integrate and interpret incoming signals from the different metabolic lipid pathways. Taken together, the large number of lipids that can activate, sensitize or inhibit neuronal TRP-channels highlights the pivotal role of these molecules in sensory biology as well as in pain transduction and perception. This article is part of a Special Issue entitled: Lipid-protein interactions. Guest Editors: Amitabha Chattopadhyay and Jean-Marie Ruysschaert.

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“…20) TRPV1 channel is a non-selective cation channel, which serves as a pain receptor, and is activated by capsaicin, increased temperature (>43°C), oxidative stress, or hypertonicity. 21,22) However, the role of TRPV1 channel in radiation-induced cellular responses has not been clarified. Therefore, in this study, we investigated the radio-sensitizing effect of TRPV1 channel inhibitors in cancer cells.…”

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Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

Nishino

Tanamachi

Nakanishi

et al. 2016

Biological & Pharmaceutical Bulletin

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Radiosensitizers are used in cancer therapy to increase the γ-irradiation susceptibility of cancer cells, including radioresistant hypoxic cancer cells within solid tumors, so that radiotherapy can be applied at doses sufficiently low to minimize damage to adjacent normal tissues. Radiation-induced DNA damage is repaired by multiple repair systems, and therefore these systems are potential targets for radiosensitizers. We recently reported that the transient receptor potential vanilloid type 1 (TRPV1) channel is involved in early responses to DNA damage after γ-irradiation of human lung adenocarcinoma A549 cells. Therefore, we hypothesized that TRPV1 channel inhibitors would have a radiosensitizing effect by blocking repair of radiation-induced cell damage. Here, we show that pretreatment of A549 cells with the TRPV1 channel inhibitors capsazepine, AMG9810, SB366791 and BCTC suppressed the γ-ray-induced activation of early DNA damage responses, i.e., activation of the protein kinase ataxia-telangiectasia mutated (ATM) and accumulation of p53-binding protein 1 (53BP1). Further, the decrease of survival fraction at one week after γ-irradiation (2.0 Gy) was enhanced by pretreatment of cells with these inhibitors. On the other hand, inhibitor pretreatment did not affect cell viability, the number of apoptotic or necrotic cells, or DNA synthesis at 24 h after irradiation. These results suggest that inhibition of DNA repair by TRPV1 channel inhibitors in irradiated A549 cells caused gradual loss of proliferative ability, rather than acute facilitation of apoptosis or necrosis. TRPV1 channel inhibitors could be novel candidates for radiosensitizers to improve the efficacy of radiation therapy, either alone or in combination with other types of radiosensitizers. Key words γ-ray; radiosensitizer; transient receptor potential vanilloid type 1 channelRadiation therapy plays an important role in treatment of numerous cancers, 1) because ionizing radiation induces potentially lethal DNA damage, such as DNA double-strand breaks (DSBs). Although DSBs cause cell death or genomic instability, 2,3) they can be repaired by mechanisms such as non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ rejoins the DNA ends without requiring sequence homologies, and is mediated by a DNA-dependent protein kinase holoenzyme. On the other hand, HR processes use undamaged homologous DNA sequences (sister chromatid or the homologous chromosome) to ensure the fidelity of the repair process. [4][5][6] The DNA damage response pathways protect genomic integrity and act as a barrier against cancer, 7) and are important for recovery of irradiated normal cells. However, overexpression of DNA repair proteins is involved in radioresistance of cancer cells, [8][9][10] and therefore these mechanisms also decrease the efficiency of radiation therapy.Since ionizing radiation does not discriminate between cancer cells and normal cells, damage to normal tissues is usually a dose-limiting factor in radiation therapy. In addition, many solid ...

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Advances in modulating thermosensory TRP channels

Cited by 83 publications

References 97 publications

Lipids as central modulators of sensory TRP channels

Lipids as central modulators of sensory TRP channels

TRP channels interaction with lipids and its implications in disease

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

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