IHC image of CSB-RA186773A0HU diluted at 1:100 and staining in paraffin-embedded human prostate cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration. Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.
基因功能參考文獻:
Study shows the cloning and characterization of N-terminal truncated TRPM8 isoforms in prostate epithelial cells and tumors. These isoforms exhibit likely 4TM domain structure which is distinct from the 6-TM of the TRP channel archetype. MTRPM8 isoforms act as the ER Ca2+-release channels not only in epidermis but also in prostate epithelial cells. PMID: 29678654
The present data suggest a possible theoretical foundation for the anti-inflammatory role of TRPM8 activation, providing an experimental basis that could contribute to the advancement of cooling therapy for trauma patients. PMID: 28332601
Study shows that TRPM8 expression is significantly up-regulated in pancreatic cancer. PMID: 29860264
Data show evidence of recent local ambient temperature adaptation on the cation channel TRPM8. PMID: 29723195
TRPM8 levels may be elevated in basal breast cancers, however, TRPM8 expression appears to be lost in many breast cancer cell lines PMID: 29496495
In this study, we identify non-channel cytoplasmic small TRPM8 isoforms as putative regulator of PCa cell death PMID: 27074561
Praziquantel is a relatively potent and selective partial agonist of the mammalian and avian cold and menthol receptor TRPM8. PMID: 29054683
The TRPM8 transient receptor potential channel. PMID: 28693898
our results indicate that enhanced TRPM8 hydrolysis in prostate cancer could present an adaptation mechanism, sustained via bypassing testosterone-induced rapid Ca2+ uptake through TRPM8, thus, diminishing the rates of apoptosis PMID: 28039451
Suggest a novel, pore-independent molecular mechanism by which endogenous TRPM8 expression inhibits Rap1 GTPase and thus plays a critical role in the behavior of vascular endothelial cells by inhibiting migration. PMID: 28550110
in this study, the glycosylation status of the TRPM8 channel was shown to affect cell proliferation, cell migration, and calcium uptake. TRPM8 expressed in the membrane of the Panc-1 pancreatic tumoral cell line is non-glycosylated, whereas human embryonic kidney cells transfected with human TRPM8 overexpress a glycosylated protein. PMID: 28857015
This study demonstrates that TRPM8 (cold receptor) is present in nasal epithelium. When it is activated by moderate cooling at 24 degrees C or menthol, TRPM8 induces the secretion of mucin. This study determines that TRPM8 channels are important regulators of mucin production. Therefore, TRPM8 antagonists could be used for the treatment of refractory rhinitis. PMID: 28767579
This study suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation. PMID: 27317670
TRPM8 SNPs are significantly associated with the risk of COPD in the Chinese Han population. PMID: 27789940
findings demonstrate that both the eTRPM8 expression level and the modalities of cold-stimulation serve as important determinants of the keratinocyte fate and act via fine tuning of [ATP] and [O2*] PMID: 27014839
TRPM8 activation is likely to occur when cigarettes contain more than 50 micrograms of menthol. PMID: 28238800
This review outlines our current understanding on the role of TRPM8 in occurrence and development of different kinds of tumor and also includes discussion about the regulation of TRPM8 during carcinogenesis as well as therapeutic potential of targeting TRPM8 in tumor, which may be utilized for a potential pharmacological use as a target for anti-cancer therapy.[review] PMID: 26803314
The effects of specific agents on TRPV1 and TRPM8 channels are intricately interrelated. PMID: 26645885
The data of this study provided evidence for decreased activity and expression level of TRPM8 in the presence of methylglyoxal. PMID: 26629685
Study used a combination of molecular modeling and experimental techniques to examine the structure of the TRPM8 transmembrane and pore helix region including the conducting conformation of the selectivity filter PMID: 26536261
Translational and clinical investigation to exploit TRPM8 as a molecular biomarker and therapeutic target is expected to make a positive impact on precision medicine in pancreatic cancer and other malignant diseases. PMID: 27038374
Several TRPM8 variants appeared to be poorly expressed in transfected HEK293 cells compared with non-mutated TRPM8. PMID: 26330615
The GC variant of the TRPM8: c.750G > C (rs11562975) polymorphism is associated with cold-induced airway hyperresponsiveness in patients with bronchial asthma. PMID: 26272603
we found that the androgen-mediated TRPM8 channel activity is negatively regulated by the androgen receptor protein PMID: 25980497
TRPM8 underlines the important physiologic role of the nose in temperature regulation, both in patients with allergy and those without allergy. Isometric contraction studies demonstrate the role of TRPM8 in regulating nasal patency and airway resistance. PMID: 26163239
These results are the first to show that menthol directly binds to the TRPM8 sensing domain. PMID: 26653082
Genetic polymorphisms in TRPM8 genes modify individual susceptibility to metabolic syndrome in a Turkish population. PMID: 25967713
developed a new functional knockout mouse strain by deleting the pore domain of TRPM8 and demonstrated that eTRPM8 knockout impairs adaptation of the epidermis to low temperatures PMID: 26080404
Antibodies against TRPM8 are not found in scleroderma patient sera, suggesting that the abnormal cold sensitivity and associated abnormal vascular reactivity in scleroderma patients is not the result of an immune process targeting TRPM8. PMID: 26242276
TRPM8 and TRPA1 assays were inhibited by probenecid. PMID: 24975826
Polymorphisms L250L and S419N correlate with anthropometric parameters (body mass index and waist and hip circumferences). PMID: 25348565
Results suggests that the aberrantly expressed TRPM8 channel may contribute to pancreatic tumorigenesis by preventing oncogene-induced senescence. PMID: 22555807
activation of TRPM8 inhibits UV-B-induced PGE2 production in keratinocytes PMID: 24580132
Over-expression of TRPM8 is associated with urothelial carcinoma of bladder. PMID: 25128062
The results indicate that the TRPM8 channel is physically associated with testosterone and suggest that, in addition to a genomic role, testosterone plays a role in direct regulation of the TRPM8 channel function. PMID: 25480783
This review focus is on TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water retention and their role in chronic inflammatory diseases. [review] PMID: 24871046
Identified two regions within the initial N terminus of TRPM8 that contribute differently to channel activity and proper folding and assembly. Deletion or substitution of the first 40 residues yielded channels with augmented responses to cold and menthol. PMID: 24917670
Data indicate that transient receptor potential melastatin 8 (TRPM8) modulates the migration of pancreatic ductal adenocarcinoma (PDA) cells. PMID: 24658318
our study provides a mechanistic insight into how TRPM8 promotes the hypoxic growth adaptation of cancer cells via its promotion of RACK1-mediated stabilization of HIF-1alpha PMID: 25065497
Data indicate that upregulation of TRPM cation channel TRPM8 promoted epithelial-mesenchymal transition of breast cancer cells via activating c-akt protein/glycogen synthase kinase 3 beta (GSK-3beta) pathway. PMID: 24903376
The subjects with homozygous genotype GG of TRPM8 had a lower cold sensation and adequate response to local skin cooling in respect to thermoregulation--decrease in respiratory heat loss and increase in the lipid metabolism PMID: 25272712
Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production. PMID: 24342393
The cold receptor transient receptor potential melastatin 8 (TRPM8) undergoes a complex modulation by clinical concentrations of VAs in dorsal root ganglion neurons and HEK-293 cells heterologously expressing TRPM8. PMID: 23943870
In uveal melanoma cells, TRPV1, TRPA1 and TRPM8 gene expression were identified. PMID: 24084605
Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. PMID: 23911290
our data suggest that TRPM8 induces UCP2 to trigger metabolic transformation, whereas TRPA1 induces autophagy during adverse conditions, and the combination of both genes contributes directly to an invasive phenotype in lung cancer. PMID: 24037916
TRPM8 is activated by camphor in a concentration- and temperature-dependent manner. PMID: 23828908
Rhinovirus infection causes upregulation of neuronal TRPM8 expression mediated directly by replicating virus. PMID: 24002057