欢迎来到抗癌健康网!  
放入收藏夹 | 返回首页

发现病毒调节糖代谢通路

2019-06-04

抗癌健康网

手机看网页

导读:最近的研究发现,人类嗜神经病毒JCV广泛存在于包括成神经管细胞瘤的大多数脑瘤。

最近的研究发现,人类嗜神经病毒JCV广泛存在于包括成神经管细胞瘤的大多数脑瘤

已知T抗原是JCV的一种早期蛋白,在细胞培养及转基因小鼠中由于它的转化活性,导致了广泛的神经嵴肿瘤及神经胶质瘤的发生。

T抗原与广泛的肿瘤抑制蛋白(包括p53、pRb以及信号分子β-catenin及IRS-1)的联系,在JCV T抗原的致癌功能中起着重要作用。

成神经管细胞瘤细胞及胶质母细胞瘤异种移植都能内源性的表达T抗原。来自美国天普大学医学院院长的研究人员最近发现,在这两种瘤细胞中,T抗原的表达通过葡萄糖剥夺(glucose deprivation)被抑制。

AMP激酶(AMPK)是细胞内一个重要的AMP/ATP感受器,研究表明,葡萄糖剥夺介导的T抗原的抑制作用在一定程度上受到5′激活的AMP激酶(AMPK)的影响。

而且在葡萄糖剥夺期间,T抗原阻止了G1停滞,并维持细胞在G2期。在功能水平上,葡萄糖剥夺期间T抗原的下调在一定程度上依赖于活性氧(ROS)的水平,T抗原阻止了ROS的诱导,导致ATP的消耗,随即表现出了细胞毒性。

此外,研究人员已经发现,T抗原被下调通过一个糖酵解抑制剂(2-脱氧-D-葡萄糖(2-DG))以及戊糖磷酸酶抑制剂(6-氨基烟酰胺及羟基硫胺素)。T抗原调节了糖酵解酶、己糖激酶2(HK2)、戊糖磷酸酶及醛羧移转酶1(TALDO1)的表达,表明了T抗原与代谢调节之间一个潜在的联系。

这些研究指出了JCV T抗原在成神经管细胞瘤增殖和代谢表型之间可能的联系。该研究增强了对病毒蛋白在糖分解代谢中的作用的理解,也提供了有用的由病毒引起的肿瘤的治疗靶点。相关论文发表在4月9日的Plos One。(生物谷Deepblue编译)

doi: 10.1371/journal.pone.0035054
PMC:
PMID:

JC Virus T-Antigen Regulates Glucose Metabolic Pathways in Brain Tumor Cells

Evan Noch, Ilker Kudret Sariyer, Jennifer Gordon, Kamel Khalili.

Recent studies have reported the detection of the human neurotropic virus, JCV, in a significant population of brain tumors, including medulloblastomas.
Accordingly, expression of the JCV early protein, T-antigen, which has transforming activity in cell culture and in transgenic mice, results in the development of a broad range of tumors of neural crest and glial origin.Evidently, the association of T-antigen with a range of tumor-suppressor proteins, including p53 and pRb, and signaling molecules, such as β-catenin and IRS-1, plays a role in the oncogenic function of JCV T-antigen.We demonstrate that T-antigen expression is suppressed by glucose deprivation in medulloblastoma cells and in glioblastoma xenografts that both endogenously express T-antigen.Mechanistic studies indicate that glucose deprivation-mediated suppression of T-antigen is partly influenced by 5′-activated AMP kinase (AMPK), an important sensor of the AMP/ATP ratio in cells.In addition, glucose deprivation-induced cell cycle arrest in the G1 phase is blocked with AMPK inhibition, which also prevents T-antigen downregulation.Furthermore, T-antigen prevents G1 arrest and sustains cells in the G2 phase during glucose deprivation. On a functional level, T-antigen downregulation is partially dependent on reactive oxygen species (ROS) production during glucose deprivation, and T-antigen prevents ROS induction, loss of ATP production, and cytotoxicity induced by glucose deprivation.Additionally, we have found that T-antigen is downregulated by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the pentose phosphate inhibitors, 6-aminonicotinamide and oxythiamine, and that T-antigen modulates expression of the glycolytic enzyme, hexokinase 2 (HK2), and the pentose phosphate enzyme, transaldolase-1 (TALDO1), indicating a potential link between T-antigen and metabolic regulation.These studies point to the possible involvement of JCV T-antigen in medulloblastoma proliferation and the metabolic phenotype and may enhance our understanding of the role of viral proteins in glycolytic tumor metabolism, thus providing useful targets for the treatment of virus-induced tumors.

文章转载于网络,仅供阅读浏览,未做任何商业用途,如有侵权请联系删除!

相关推荐:

在这里,掌握健康资讯

扫描左侧二维码即可添加抗癌健康网官方微信;
健康之路 与你同行
卵巢癌更多>>
热文欣赏更多>>

健康阅读

推荐欣赏

  • 热门推荐
  • 最新期刊
  • 疾病关注
长期憋尿,膀胱癌,长期憋尿引发膀胱癌
[详情]
白血病与骨髓移植术
[详情]
筷子致癌?靠什么吃饭?
[详情]
卵巢囊肿并不可怕
[详情]
调理内分泌多吃黄色食物
[详情]
吃腐乳致癌可信吗?
[详情]
资讯排行榜更多>>
肺癌康复指南吃什么?
信息聚焦更多>>
化疗药物中成药止痛药
奥沙利铂参丹散结胶囊阿司匹林
紫杉醇臌症丸扑热息痛
卡铂贞芪扶正颗粒盐酸哌替啶片
泰素阿魏化痞膏吗啡
氟尿嘧啶软膏西黄丸芬太尼
视频推荐更多>>
肿瘤热文欣赏更多>>

特别声明:本站信息仅供参考 不能作为诊断及医疗的依据平台联系我们

抗癌健康网 版权所有 未经授权请勿转载  CopyRight©2008-2018 www.ca39.com, All Rights Reserved. 浙ICP备11014848号