Several members of the transient receptor potential (TRP)-channel family are expressed in cancer cells. One, cold/menthol-sensitive TRPM8, is reportedly an important player in carcinogenesis in human ...prostate cancer, although its involvement in oral squamous cell carcinoma (SCC) remains unclear. The present immunohistochemistry and RT-PCR results revealed intense TRPM8 expression in two SCC cell lines, HSC3 and HSC4, derived from the human tongue. Menthol, icilin, and a more specific TRPM8 agonist (WS-12) induced non-specific cation currents, with Ca2+ permeability being greater than that of Na+ or K+. The novel TRPM8 antagonist RQ-00203078 (RQ) profoundly reduced such agonist-induced cation currents. Intracellular Ca2+ imaging revealed that menthol induced both intracellular Ca2+ release and store-operated Ca2+ entry, with RQ inhibiting each effect. To assess the possible pathophysiological role of TRPM8 in oral SCC, we performed motility and invasion assays, and gelatin zymography. Menthol augmented the migration and invasion abilities of both HSC3 and HSC4 cells by potentiating MMP-9 activity. RQ suppressed all of these effects. These results may aid understanding of the pathophysiological implications of TRPM8 channels in the oral SCC cells, support TRP proteins as valuable targets for pharmaceutical intervention, and inform the targeting of oral SCC in which the prognosis is poor.
An autopsy of a patient in Japan with coronavirus disease indicated pneumonia lung pathology, manifested as diffuse alveolar damage. We detected severe acute respiratory syndrome coronavirus 2 ...antigen in alveolar epithelial cells and macrophages. Coronavirus disease is essentially a lower respiratory tract disease characterized by direct viral injury of alveolar epithelial cells.
Brown and beige adipocytes are a major site of mammalian non-shivering thermogenesis and energy dissipation. Obesity is caused by an imbalance between energy intake and expenditure and has become a ...worldwide health problem. Therefore modulation of thermogenesis in brown and beige adipocytes could be an important application for body weight control and obesity prevention. Over the last few decades, the involvement of thermo-sensitive transient receptor potential (TRP) channels (including TRPV1, TRPV2, TRPV3, TRPV4, TRPM4, TRPM8, TRPC5, and TRPA1) in energy metabolism and adipogenesis in adipocytes has been extensively explored. In this review, we summarize the expression, function, and pathological/physiological contributions of these TRP channels and discuss their potential as future therapeutic targets for preventing and combating human obesity and obesity-related metabolic disorders.
To date, 11 thermosensitive transient receptor potential (thermo-TRP) channels have been identified. Recent studies have characterized the mechanism of thermosensing by thermo-TRPs and the ...physiological role of thermo-TRPs in energy metabolism. In this review, we highlight the role of various thermo-TRPs in energy metabolism and hormone secretion. In the pancreas, TRPM2 and other TRPs regulate insulin secretion. TRPV2 expressed in brown adipocytes contributes to differentiation and/or thermogenesis. Sensory nerves that express TRPV1 promote increased energy expenditure by activating sympathetic nerves and adrenaline secretion. Here, we first show that capsaicin-induced adrenaline secretion is completely impaired in TRPV1 knockout mice. The thermogenic effects of TRPV1 agonists are attributable to brown adipose tissue (BAT) activation in mice and humans. Moreover, TRPA1- and TRPM8-expressing sensory nerves also contribute to potentiation of BAT thermogenesis and energy expenditure in mice. Together, thermo-TRPs are promising targets for combating obesity and metabolic disorders.
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective cation channel that is activated by a variety of stimuli and acts as a nociceptor. Mouse and human TRPA1 exhibit different reactivity ...to some stimuli, including chemicals such as menthol as well as cold stimuli. The cold sensitivity of TRPA1 in mammalian species is controversial. Here, we analyzed the reactivity of heterologously expressed canine TRPA1 as well as the mouse and human orthologs to menthol or cold stimulation in Ca2+-imaging experiments. Canine and human TRPA1 exhibited a similar response to menthol, that is, activation in a concentration-dependent manner, even at the high concentration range in contrast to the mouse ortholog, which did not respond to high concentration of menthol. In addition, the response during the removal of menthol was different; mouse TRPA1-expressing cells exhibited a typical response with a rapid and clear increase in Ca2+i (“off-response”), whereas Ca2+i in human TRPA1-expressing cells was dramatically decreased by the washout of menthol and Ca2+i in canine TRPA1-expressing cells was slightly decreased. Finally, canine TRPA1 as well as mouse and human TRPA1 were activated by cold stimulation (below 19–20°C). The sensitivity to cold stimulation differed between these species, that is, human TRPA1 activated at higher temperatures compared with the canine and mouse orthologs. All of the above responses were suppressed by the selective TRPA1 inhibitor HC-030031. Because the concentration-dependency and “off-response” of menthol as well as the cold sensitivity were not uniform among these species, studies of canine TRPA1 might be useful for understanding the species-specific functional properties of mammalian TRPA1.
Computed Tomography (CT) using X-ray attenuation by atomic effects is now widely used for medical diagnosis and industrial non-destructive inspection. In this study, we performed a tomographic ...imaging of isotope (208Pb) distribution by the Nuclear Resonance Fluorescence (NRF), i.e. isotope specific resonant absorption and scattering of gamma rays, using Laser Compton Scattering (LCS) gamma rays. The NRF-CT image which includes both effects of atomic attenuation and nuclear resonant attenuation was obtained. By accounting for the atomic attenuation measured by a conventional method at the same time, a clear 208Pb isotope CT image was obtained. The contrast degradation due to notch refilling caused by small-angle Compton scattering is discussed. This study clearly demonstrates the capability of the isotope-specific CT imaging based on nuclear resonant attenuation which will be a realistic technique when the next generation of extremely intense LCS gamma-ray sources will be available. The expected image acquisition time using these intense LCS gamma rays was discussed.
Epithelial-mesenchymal transition (EMT) is a biological event in which epithelial cells lose their polarity and cell–cell adhesions and concomitantly acquire mesenchymal traits, and is thought to ...play an important role in pathological processes such as wound healing and cancer progression. In this study, we evaluated transforming growth factor (TGF)-β1-treated human keratinocyte HaCaT cells as an in vitro model of EMT. HaCaT cells were changed into an elongated fibroblast-like morphology, which is indicative of EMT in response to TGF-β1. Phalloidin staining demonstrated the formation of actin stress fibers in TGF-β1-treated cells. Quantitative RT-PCR analysis revealed that TGF-β1 increased the mRNA levels of EMT transcription factors (SNAI2, TWIST1, and ZEB1) and mesenchymal markers (CDH2, VIM, and FN1), while it decreased the transcripts of epithelial phenotypic genes (CLDN1, OCLN, KRT5, KRT15, KRT13, and TGM1). Furthermore, we found that KRT13 was drastically suppressed through the reduction of RNA polymerase II occupancy of its promoter, which was accompanied by a decrease in active histone marks (H3K4me3 and H3K27ac) and an increase in a repressive mark (H3K27me3) during EMT. These findings indicate that the TGF-β1-induced EMT program regulates a subset of epithelial and mesenchymal marker genes, and that KRT13 is transcriptionally suppressed through the modulation of the chromatin state at the KRT13 promoter in HaCaT cells.
•TGF-β1 induced mesenchymal-like morphology in HaCaT cells.•TGF-β1-induced EMT partially controlled the gene expression of EMT markers.•KRT13 was identified as a TGF-β1-responsive epithelial marker in HaCaT cells.•Chromatin state of the KRT13 promoter was epigenetically regulated during EMT.
Certain methanogens deteriorate steel surfaces through a process called microbiologically influenced corrosion (MIC). However, the mechanisms of MIC, whereby methanogens oxidize zerovalent iron (Fe
...), are largely unknown. In this study, Fe
-corroding Methanococcus maripaludis strain OS7 and its derivative (strain OS7mut1) defective in Fe
-corroding activity were isolated. Genomic analysis of these strains demonstrated that the strain OS7mut1 contained a 12-kb chromosomal deletion. The deleted region, termed "MIC island", encoded the genes for the large and small subunits of a NiFe hydrogenase, the TatA/TatC genes necessary for the secretion of the NiFe hydrogenase, and a gene for the hydrogenase maturation protease. Thus, the NiFe hydrogenase may be secreted outside the cytoplasmic membrane, where the NiFe hydrogenase can make direct contact with Fe
, and oxidize it, generating hydrogen gas: Fe
+ 2 H
→ Fe
+ H
. Comparative analysis of extracellular and intracellular proteomes of strain OS7 supported this hypothesis. The identification of the MIC genes enables the development of molecular tools to monitor epidemiology, and to perform surveillance and risk assessment of MIC-inducing M. maripaludis.
•Role of TRP channels in wound contracture is elucidated using a reconstruction model.•Keratinocyte-derived TGF-β1 secretion and fibroblast differentiation are clarified.•TRPV2 inhibitors attenuate ...TGF-β-mediated contraction of the model.•TRPV2 channels are markedly expressed in this model.•TRPV2 is a possible promising target to ameliorate scar formation.
Keratinocytes release several factors that are involved in wound contracture and scar formation. We previously reported that a three-dimensional reconstruction model derived from rat skin represents a good wound healing model.
We characterized the role of transient receptor potential (TRP) channels in the release of transforming growth factor (TGF)-β1 from keratinocytes and the differentiation of fibroblasts to identify possible promising pharmacological approaches to prevent scar formation and contractures.
The three-dimensional culture model was made from rat keratinocytes seeded on a collagen gel in which dermal fibroblasts had been embedded.
Among the TRP channel inhibitors tested, the TRPV2 inhibitors SKF96365 and tranilast attenuated most potently keratinocyte-dependent and — independent collagen gel contraction due to TGF-β signaling as well as TGF-β1 release from keratinocytes and α-smooth muscle actin production in myofibroblasts. Besides the low amounts detected in normal dermis, TRPV2 mRNA and protein levels were increased after fibroblasts were embedded in the gel. TRPV2 was also expressed in the epidermis and keratinocyte layers of the model. Both inhibitors and TRPV2 siRNA attenuated the intracellular increase of Ca2+ induced by the TRPV agonist 2-aminoethoxydiphenyl borate in TGF-β1-pretreated fibroblasts.
This is the first study to show that compounds targeting TRPV2 channels ameliorate wound contraction through the inhibition of TGF-β1 release and the differentiation of dermal fibroblasts in a culture model.
The regulatory effect of light quality on the photosynthetic apparatus in attached leaves of rice plants was investigated by keeping rice plants under natural light, in complete darkness, or under ...illumination with light of different colors. When leaves were left in darkness and far-red (FR)-light conditions for 6 days at 30°C, there was an initial lag in chlorophyll (Chl) content, Chl a/b ratio, and maximum photosystem (PS) II photochemistry that lasted until the second day; these then rapidly decreased on the fourth day. In contrast, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) rapidly disappeared with no lag under low or zero light conditions. By using spectrophotometric quantitation, it was determined that the PSII and PSI reaction centers were regulated by light quality, but cytochrome (Cyt) f was regulated by light intensity. However, the PSII heterogeneity was also strongly modified by the light intensity; PSIIα with the large antenna decreased markedly both in content and in antenna size. Consequently, the PSIIα/PSI ratio declined under FR-light because the low intensity of FR-light dominated over its quality in the modulation of the PSIIα/PSI ratio. An imbalance between them induced the generation of reactive oxygen species (ROS), although the ROS were scavenged by stromal enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR). The activities of these stromal enzymes are also regulated by light quality. Thus, although the photosynthetic apparatus is regulated differently depending on light quality, light quality may play an important role in the regulation of the photosynthetic apparatus.
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![An extracellular [NiFe] hyd...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/2045-2322/small "An extracellular [NiFe] hydrogenase mediating iron corrosion is encoded in a genetically unstable genomic island in Methanococcus maripaludis")
