Cannabinoids inhibit gap junctional intercellular communication and activate ERK in a rat liver epithelial cell line.
Cannabinoids inhibit gap junctional intercellular communication and activate ERK in a rat liver epithelial cell line.
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大麻素抑制大鼠肝上皮细胞系中间隙连接细胞间通讯并激活 ERK。
DOI：
10.1002/ijc.10899
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发表时间：
2003
影响因子：
6.4
通讯作者：
Kaminski,NorbertE
中科院分区：
文献类型：
--
作者：
Upham,BradL;Rummel,AlisaM;Carbone,JosephM;Trosko,JamesE;Ouyang,Yanli;Crawford,RobertB;Kaminski,NorbertE
许多肿瘤促进剂抑制免疫系统;然而，免疫抑制剂对实体组织中非免疫细胞的致瘤途径的直接影响尚未得到很好的证明。选择大麻素来进一步探讨这个问题。大麻素是影响白细胞中特定细胞内信号传导途径的免疫调节剂。由于这些化合物无遗传毒性，因此可能与这些化合物相关的任何致瘤效应都需要通过表观遗传机制发生。因此，我们确定了Δ9-THC和CBN（2种植物来源的大麻素）对肿瘤促进的2个关键表观遗传标志物的影响：抑制GJIC，这对于消除细胞生长抑制至关重要，以及激活ERK-MAPK通路，这对于激活适当的基因进行有丝分裂至关重要。在正常二倍体WB大鼠肝上皮卵圆细胞系中，Δ9-THC和CBN在20 min内以非细胞毒性剂量（15 μM）可逆地抑制GJIC，并在5 min内激活ERK 1和ERK 2。使用PD 98059抑制MEK可阻止大麻素对GJIC的抑制，表明GJIC的抑制是MEK依赖性的。基于RT-PCR分析和CB 1和CB 2拮抗剂的使用，对GJIC和MAPK的影响独立于两种大麻素受体。大麻素影响啮齿动物肝上皮细胞模型系统中与细胞增殖相关的关键表观遗传途径。© 2002 Wiley利斯公司
Many tumor promoters suppress the immune system; however, the direct effect of immunosuppressants on the tumorigenic pathways of nonimmune cells in solid tissue has not been well documented. Cannabinoids were chosen to explore this question further. Cannabinoids are immune modulators that affect specific intracellular signaling pathways in leukocytes. Since these compounds are nongenotoxic, any tumorigenic effect that might be associated with these compounds would need to occur through an epigenetic mechanism. Therefore, we determined the effect of Δ9‐THC and CBN, 2 plant‐derived cannabinoids, on 2 key epigenetic markers of tumor promotion: inhibition of GJIC, which is essential in removing a cell from growth suppression, and activation of the ERK–MAPK pathway, which is crucial in activating the appropriate genes for mitogenesis. Both Δ9‐THC and CBN reversibly inhibited GJIC at noncytotoxic doses (15 μM) in a normal diploid WB rat liver epithelial oval cell line within 20 min and activated ERK1 and ERK2 within 5 min. Inhibition of MEK with PD98059 prevented the inhibition of GJIC by either cannabinoid, suggesting that inhibition of GJIC was MEK‐dependent. Based on RT‐PCR analysis and employment of an antagonist of CB1 and CB2, the effects on GJIC and MAPK were independent of both cannabinoid receptors. Cannabinoids affected crucial epigenetic pathways associated with cell proliferation in a rodent liver epithelial cell model system. © 2002 Wiley‐Liss, Inc.
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影响因子：
3.8
作者：
GUAN, XJ;BONNEY, WJ;RUCH, RJ
通讯作者：
RUCH, RJ
DOI：
10.2741/a275
发表时间：
1998-02
期刊：
Frontiers in bioscience : a journal and virtual library
影响因子：
--
作者：
J. Trosko;R. Ruch
通讯作者：
J. Trosko;R. Ruch
影响因子：
4.1
作者：
Bolton, JL;Trush, MA;Monks, TJ
通讯作者：
Monks, TJ
影响因子：
56.9
作者：
Unger, VM;Kumar, NM;Yeager, M
通讯作者：
Yeager, M
在长期原代培养的大鼠肝细胞中，巴比妥类药物对间隙连接细胞间通讯的抑制与肝脏肿瘤促进活性相关。
影响因子：
4.7
作者：
Ren,P;Ruch,RJ
通讯作者：
Ruch,RJ