![]() ![]() ![]() In Drosophila, photoreceptors and mammalian photosensitive retinal ganglion cell phototransduction is mediated by G protein-activated phospholipase C (PLC), which generates a force in the lipid-bilayer opening TRP-Canonical channels. Additionally, TRP channels are mechanically activated directly or by signaling cascades that alter lipid composition, change conformation of plasma membrane and open TRPs by mechanical force (reviewed in Liu and Montell 22). 21 showed that the oxidative status of Cys residues in the TRPV1 sequence modulated by reactive oxygen species triggers TRPV1 activation through changes in the redox environment. Allosteric coupling between both domains is responsible for a broad physiological range of stimuli activating TRPV1 and other TRP channels. High-resolution analysis of TRPV1 structure identified conformational changes in an outer pore domain and lower gate domain through ligand-binding. 18 However, diverse TRPV1 activation mechanisms induced through various (physical) stimuli have not yet been elucidated. 17 Transient receptor potential V1 mediates heat shock–induced matrix metalloproteinase-1 (MMP-1) expression in human keratinocytes. 14 – 16 Furthermore, changes of TRPV1 expression (in human skin) can be detected after UV irradiation. 12, 13 Besides being activated by heat (>43☌) and CAP, exposure to acidity and hyperosmolarity can also induce this response. The heat-sensitive TRP vanilloid receptor 1 (TRPV1, capsaicin receptor) channel is the most investigated TRP channel and it is the only one whose three-dimensional structure was determined. Transient receptor potential (TRP) channels constitute a superfamily of ligand-gated, nonselective cation channels subdivided into seven subfamilies according to differences in amino acid sequence homology (reviewed by Ramsey et al. In the long term, it often results in reduced vision due to astigmatism, tear film alterations, and movement restriction of the bulbus. 7 Advanced pterygium frequently leads to precorneal tear film dysfunction and dry eye disease (DES). Because of its high recurrence rate (10%–70%), often repeated surgery may be needed, which heightens the likelihood of regrowth, inflammation, and scar formation. 1, 3 – 6 Surgical resection is the only option for reducing visual impairment caused by a pterygium-related disturbance. 1, 2 Specifically, pterygium incidence is greater in regions near the equator (pterygium belt), 1, 3 – 5 whereas in Europe it is substantially less. In addition, viral infection and genetic factors contribute to initiating and promoting this disease. Its risk factors include not only dust, wind, heat, dryness, and smoke, but also chronic UV-B light exposure, which is the main risk factor. Pterygium (conjunctivae) is a common ocular surface hyperproliferative tumorous disorder. Therefore, TRPV1 is a potential drug target whose clinical relevance in treating pterygium warrants further assessment. Only in hPtEC do the increases in proliferation induced by EGF exceed those in HCjEC. Mitogenic responses to EGF and VEGF are mediated through TRPV1 transactivation. Capsazepine suppressed hPtEC proliferation induced by EGF and VEGF, whereas it was cytotoxic to HCjEC. Whereas epidermal growth factor (EGF) increased proliferation more in hPtEC than in HCjEC, VEGF had no effect on this response. Vascular endothelial growth factor (VEGF) also increased Ca 2+-influx and induced corresponding inward currents more in hPtEC than in HCjEC, whereas CPZ (20 μM), BCTC (20 μM), or La 3+ (500 μM) reduced these responses, respectively. Capsaicin induced corresponding changes in inward currents that were inhibited by 20 μM capsazepine (CPZ). An MTS assay measured cell metabolic activity and a cell growth assay monitored proliferation.Ĭapsaicin (20 μM) and elevating bath temperature above 43☌ activated Ca 2+ transients more in hPtEC than HCjEC. ![]() Imaging of Ca 2+ and planar whole-cell patch-clamping evaluated TRP channel activity. Reverse transcriptase PCR and quantitative real-time PCR, along with immunohistochemistry and Western blotting, characterized TRPV1 expression patterns in pterygial and healthy conjunctival tissue, primary and immortalized pterygial cells (hPtEC), and primary and immortalized conjunctival epithelial cells (HCjEC). This study determined if this response occurs in fresh and cultured hyperplastic human pterygial epithelial tissues. The heat-sensitive transient receptor potential vanilloid type-1 (TRPV1) channel (i.e., capsaicin receptor) is upregulated in numerous cancers. ![]()
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