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| Content Provider | Springer Nature Link |
|---|---|
| Author | Tian, Yangyang Yang, Yang Zhang, Xiaowei Nakajima, Takero Tanaka, Naoki Sugiyama, Eiko Kamijo, Yuji Lu, Yu Moriya, Kyoji Koike, Kazuhiko Gonzalez, Frank J. Aoyama, Toshifumi |
| Copyright Year | 2016 |
| Abstract | 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. |
| Starting Page | 927 |
| Ending Page | 936 |
| Page Count | 10 |
| File Format | |
| ISSN | 02820080 |
| Journal | Glycoconjugate Journal |
| Volume Number | 33 |
| Issue Number | 6 |
| e-ISSN | 15734986 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2016-06-18 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Cancer Core protein HCV PPARα Sphingolipid Sulfatide Biochemistry Pathology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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