Age-dependent PPARα activation induces hepatic sulfatide accumulation in transgenic mice carrying the hepatitis C virus core gene.
Age-dependent PPARα activation induces hepatic sulfatide accumulation in transgenic mice carrying the hepatitis C virus core gene.
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年龄依赖性 PPARα 激活可诱导携带丙型肝炎病毒核心基因的转基因小鼠肝脏硫苷脂积累。
DOI：
10.1007/s10719-016-9703-1
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发表时间：
2016-12
影响因子：
3
通讯作者：
Aoyama T
中科院分区：
文献类型：
--
作者：
Tian Y;Yang Y;Zhang X;Nakajima T;Tanaka N;Sugiyama E;Kamijo Y;Lu Y;Moriya K;Koike K;Gonzalez FJ;Aoyama T
硫酸脂是一种鞘糖脂，与致癌作用有关。过氧化物酶体增殖物激活受体α（PPARα）参与调节硫苷脂代谢以及癌症的发展。我们以前报道过表达丙型肝炎病毒核心蛋白（HCVcp）的转基因（Tg）小鼠在肝脏中表现出年龄依赖性的PPARα激活和致癌作用。然而，硫苷脂在肝细胞癌中的代谢尚不清楚。为了检测硫苷脂代谢、致癌作用、HCVcp和PPARα之间的关系，在HCVcpTg、经PPARα受体处理的HCVcpTg和非Tg小鼠中检测了这些因子的年龄依赖性变化。HCVcpTg小鼠肝脏中的硫苷脂含量、催化硫苷脂合成的起始和最终反应的两种关键酶的肝脏表达、已知的硫苷脂转移蛋白的肝脏表达、氧化应激以及肝脏PPARα的表达及其活化呈年龄依赖性增加。肝癌组织中硫苷合成和积累增加，过氧化物酶体增殖物激活受体α（PPARα）活性增强。这些变化通过PPARα抑制剂处理减弱，在非Tg小鼠中未观察到。这些结果表明HCVcp诱导的年龄依赖性PPARα激活增加了硫苷脂的合成，导致的硫苷脂积累影响了HCV相关的肝癌。监测肝硫脂含量和通过使用PPARα抑制剂进行干预来调节硫脂的产生可能分别用于预测和预防HCV相关的肝癌发生。
Sulfatides, a type of glycosphingolipid, are associated with carcinogenesis. Peroxisome proliferator-activated receptor α (PPARα) is involved in the regulation of sulfatide metabolism as well as in cancer development. We previously reported that transgenic (Tg) mice expressing hepatitis C virus core protein (HCVcp) exhibited age-dependent PPARα activation and carcinogenesis in liver. However, the metabolism of sulfatides in hepatocellular carcinoma is unknown. To examine the relationship between sulfatide metabolism, carcinogenesis, HCVcp, and PPARα, age-dependent changes of these factors were examined in HCVcpTg, PPARα inhibitor-treated HCVcpTg, and non-Tg mice. The sulfatide content in liver, the hepatic expression of two key enzymes catalyzing the initial and last reactions in sulfatide synthesis, the hepatic expression of known sulfatide-transferring protein, oxidative stress, and hepatic PPARα expression and its activation were age-dependently increased in HCVcpTg mice. The increased synthesis and accumulation of sulfatides and PPARα activation were significantly enhanced in liver cancer lesions. These changes were attenuated by PPARα inhibitor treatment and not observed in non-Tg mice. These results suggest that HCVcp-induced age-dependent PPARα activation increases synthesis of sulfatides and the resulting sulfatide accumulation affects HCV-related liver cancer. The monitoring of hepatic sulfatide content and the modulation of sulfatide generation by intervention using a PPARα inhibitor might be useful for the prediction and prevention of HCV-related hepatocarcinogenesis, respectively.
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影响因子：
3.6
作者：
Nakajima, Takero;Tanaka, Naoki;Aoyama, Toshifumi
通讯作者：
Aoyama, Toshifumi
DOI：
10.1073/pnas.0811269106
发表时间：
2009-05-19
影响因子：
11.1
作者：
Han, Gongshe;Gupta, Sita D.;Dunn, Teresa M.
通讯作者：
Dunn, Teresa M.
硫脂苷表观遗传调控miR-223并促进人肝细胞癌细胞的迁移
影响因子：
25.7
作者：
Dong, Yi Wei;Wang, Rong;Wu, Xing Zhong
通讯作者：
Wu, Xing Zhong
影响因子：
4.7
作者：
Peters, JM;Aoyama, T;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
4.1
作者：
NAKAJIMA, T;ELOVAARA, E;AOYAMA, T
通讯作者：
AOYAMA, T