Serotonin induced hepatic steatosis is associated with modulation of autophagy and notch signaling pathway.
Serotonin induced hepatic steatosis is associated with modulation of autophagy and notch signaling pathway.
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DOI：
10.1186/s12964-018-0282-6
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发表时间：
2018-11-08
期刊：
影响因子：
--
通讯作者：
Kumar D
中科院分区：
文献类型：
--
作者：
Niture S;Gyamfi MA;Kedir H;Arthur E;Ressom H;Deep G;Kumar D
除了其神经递质和血管收缩功能之外，5-羟色胺是外周组织中许多生物过程的重要介质，包括细胞增殖、脂肪变性和纤维化。最近的研究表明5-羟色胺可能促进肝癌的生长，但其分子机制尚不清楚。在这项研究中，我们研究了5-羟色胺在肝癌细胞存活、耐药性和脂肪变性中的作用和分子信号机制。MTT/WST 1法检测5-羟色胺对细胞存活/增殖的调节作用。通过免疫印迹评估5-羟色胺对自噬生物标志物和脂质/脂肪酸蛋白表达、AKT/mTOR和Notch信号传导的调节的作用。油红O染色分析5-羟色胺在正常人肝细胞和肝癌细胞脂肪变性中的作用。通过qRT-PCR验证脂质/脂肪酸蛋白和5-羟色胺受体的mRNA表达水平。自噬、Notch信号、5-羟色胺受体和5-羟色胺再摄取蛋白在降钙素介导的细胞脂肪变性中的重要作用通过使用选择性抑制剂或拮抗剂进行了研究。还使用慢性EtOH喂养的小鼠模型研究了外周5-羟色胺、自噬和肝脂肪变性的关联。肝癌细胞暴露于5-羟色胺诱导Notch信号传导和自噬，独立于AKT/mTOR通路。此外，血清素增强癌细胞增殖/存活和耐药性。此外，5-羟色胺治疗上调了脂肪生成蛋白的表达，并增加了肝癌细胞的脂肪变性。抑制自噬或Notch信号传导减少了胡萝卜素介导的细胞脂肪变性。用5-羟色胺受体拮抗剂5-HTr 1B和5-HTr 2B治疗可减少阿托宁介导的细胞脂肪变性;相反，用选择性5-羟色胺再摄取抑制剂（SSRIs）治疗可增加脂肪变性。此外，用慢性EtOH喂养的小鼠导致血清5-羟色胺水平增加，这与肝脂肪变性和自噬的诱导相关。5-羟色胺通过激活Notch信号和自噬调节肝癌细胞脂肪变性、细胞存活，并可能促进肝癌的发生。本文的在线版本（10.1186/s12964-018-0282-6）包含补充材料，可供授权用户使用。
Besides its neurotransmitter and vasoconstriction functions, serotonin is an important mediator of numerous biological processes in peripheral tissues including cell proliferation, steatosis, and fibrogenesis. Recent reports indicate that serotonin may promote tumor growth in liver cancer, however, the molecular mechanisms remain elusive. n this study, we investigated the role and molecular signaling mechanisms mediated by serotonin in liver cancer cell survival, drug resistance, and steatosis. Effect of serotonin on modulation of cell survival/proliferation was determined by MTT/WST1 assay. Effect of serotonin on the regulation of autophagy biomarkers and lipid/fatty acid proteins expression, AKT/mTOR and Notch signaling was evaluated by immunoblotting. The role of serotonin in normal human hepatocytes and liver cancer cell steatosis was analyzed by Oil Red O staining. The mRNA expression levels of lipid/fatty acid proteins and serotonin receptors were validated by qRT-PCR. The important roles of autophagy, Notch signaling, serotonin receptors and serotonin re-uptake proteins on serotonin-mediated cell steatosis were investigated by using selective inhibitors or antagonists. The association of peripheral serotonin, autophagy, and hepatic steatosis was also investigated using chronic EtOH fed mouse model. Exposure of liver cancer cells to serotonin induced Notch signaling and autophagy, independent of AKT/mTOR pathway. Also, serotonin enhanced cancer cell proliferation/survival and drug resistance. Furthermore, serotonin treatment up-regulated the expression of lipogenic proteins and increased steatosis in liver cancer cells. Inhibition of autophagy or Notch signaling reduced serotonin-mediated cell steatosis. Treatment with serotonin receptor antagonists 5-HTr1B and 5-HTr2B reduced serotonin-mediated cell steatosis; in contrast, treatment with selective serotonin reuptake inhibitors (SSRIs) increased steatosis. In addition, mice fed with chronic EtOH resulted in increased serum serotonin levels which were associated with the induction of hepatic steatosis and autophagy. Serotonin regulates liver cancer cell steatosis, cells survival, and may promote liver carcinogenesis by activation of Notch signaling and autophagy. The online version of this article (10.1186/s12964-018-0282-6) contains supplementary material, which is available to authorized users.
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影响因子：
29
作者：
Lin HV;Accili D
通讯作者：
Accili D
DOI：
10.1016/j.biocel.2011.10.010
发表时间：
2012-01-01
影响因子：
4
作者：
Coelho, Wagner Santos;Da Silva, Daniel;Sola-Penna, Mauro
通讯作者：
Sola-Penna, Mauro
影响因子：
4.3
作者：
Kwanten, Wilhelmus J.;Martinet, Wim;Francque, Sven M.
通讯作者：
Francque, Sven M.
影响因子：
6.6
作者：
Fatima, Sarwat;Shi, Xiaoke;Bian, Zhao Xiang
通讯作者：
Bian, Zhao Xiang
影响因子：
2.8
作者：
Morgan, CJ;Badawy, AAB
通讯作者：
Badawy, AAB