Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells.

Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells.
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人葡萄膜黑色素瘤细胞中温度敏感瞬时受体电位通道的钙调节

DOI:
10.1016/j.cellsig.2013.09.017
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发表时间:
2014
影响因子:
4.8
通讯作者:
Riechardt
Riechardt
中科院分区:
生物学2区
文献类型:
--
作者:
Mergler;Derckx;Reinach;Garreis;Schmelzer;Skosyrski;Ramesh;Abdelmessih;Khajavi;Riechardt

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葡萄膜黑色素瘤(UM)是全世界成年人中最常见和最致命的眼内癌。与所有类型的肿瘤一样,钙离子通道调节的变化可能有助于这种病理状态的发生和发展。瞬时受体电位通道(TRPs)和大麻素1型受体(CB1)是两种不同类型的钙离子渗透途径,可在肿瘤发生过程中调节失调。我们检测了人类恶性葡萄膜和健康葡萄膜以及四种不同的葡萄膜细胞系中是否存在TRP亚型和CB1的基因和功能表达,因为它们可以作为药物靶点来预防或抑制UM的发生和发展。RT-PCR、钙瞬变、免疫组织化学和平面膜片钳分析分别检测它们的基因表达和功能活性。在UM细胞中检测到TRPV1和TRPM8基因的表达。辣椒素(CAP)、薄荷醇或尼可林诱导的钙瞬变以及TRPV1和TRPM8表达的离子电流行为特征的改变。这种作用可被La3+、卡萨西平(CPZ)或BCTC阻断。TRPA1和CB1在人葡萄膜中高表达,但在所有UM细胞系中不表达。在UM细胞中,CB1激动剂Win 55,212-2诱导的钙瞬变可被La3+和CPZ抑制,而CAP诱导的钙瞬变也可被CB1激活所抑制。鉴定TRPV1、TRPM8、TRPA1和CB1在这些组织中的功能表达可能为治疗这种侵袭性肿瘤提供新的药物靶点。
Uveal melanoma (UM) is both the most common and fatal intraocular cancer among adults worldwide. As with all types of neoplasia, changes in Ca2+channel regulation can contribute to the onset and progression of this pathological condition. Transient receptor potential channels (TRPs) and cannabinoid receptor type 1 (CB1) are two different types of Ca2+permeation pathways that can be dysregulated during neoplasia. We determined in malignant human UM and healthy uvea and four different UM cell lines whether there is gene and functional expression of TRP subtypes and CB1 since they could serve as drug targets to either prevent or inhibit initiation and progression of UM. RT-PCR, Ca2+transients, immunohistochemistry and planar patch-clamp analysis probed for their gene expression and functional activity, respectively. In UM cells, TRPV1 and TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced Ca2+transients as well as changes in ion current behavior characteristic of TRPV1 and TRPM8 expression. Such effects were blocked with either La3+, capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN 55,212-2, induced Ca2+transients, which were suppressed by La3+and CPZ whereas CAP-induced Ca2+transients could also be suppressed by CB1 activation. Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these tissues may provide novel drug targets for treatment of this aggressive neoplastic disease.
DOI: 10.1016/j.exer.2010.06.022
发表时间: 2010-09
影响因子: 3.4
作者:
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8 型褪黑激素瞬时受体电位通道 (TRPM8) 的调节:cAMP、大麻素 CB(1) 受体和内香草素的作用。
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发表时间: 2007
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DOI: --
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期刊: The Journal of biological chemistry
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发表时间: 2009-09-01
影响因子: 5.5
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Devi, Sulochana;Kedlaya, Rajendra;Setaluri, Vijayasaradhi
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DOI: 10.1016/j.exer.2012.11.004
发表时间: 2013
影响因子: 3.4
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