Aberrant energy metabolism induced by iron overload; Analysis for novel carcinogenic factor in liver tissue

• Project/Area Number: 26830092
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Asahikawa Medical College
• Principal Investigator: Tanaka Hiroki 旭川医科大学, 医学部, 助教 (70596155)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 鉄過剰 / 肝癌 / 脂質代謝 / 鉄 / コレステロール合成 / エネルギー代謝

Outline of Final Research Achievements

In the iron-loaded mouse livers, genetic expression of metabolic enzymes involved in cholesterol biosynthesis, β oxidation and prenylation (Fdps, FTase) were increased. These metabolic pathways are known to modulate Ras proteins post-translationally. In mouse primary hepatocytes, although iron-induced 8OHdG production was neutralized in the presence of the anti-oxidant NAC, phosphorylation of ERK1/2 was not canceled even in the presence of NAC. However, the iron chelator, deferoxamine reduced iron-induced expression of Fdps, FTase and phospho-ERK1/2. These results clearly indicate that iron affects not only the production of oxidative damage but lipid metabolism, thereby promoting a proliferation signal in the liver.

Research Products

• [Presentation] 肝発癌における鉄過剰の新たな役割：鉄過剰が引き起こす脂質代謝異常を介した細胞増殖シグナルの亢進 (2015)
  • Author(s): 田中宏樹，澤田康司，長谷部拓夢，佐々木勝則，藤谷幹浩，大竹孝明，高後裕
  • Organizer: 第26回日本消化器癌発生学会総会
  • Place of Presentation: 米子市
  • Year and Date: 2015-11-19
• [Presentation] Iron-overload alters lipid metabolism and Ras signaling independent of oxidative stress in mouse liver tissue by whole RNA sequencing (2014)
  • Author(s): Hiroki Tanaka, Takaaki Ohtake, Lynda Addo, Masayo Yamamoto, Yasumichi Toki, Koji, Sawada, Synsuke Nakajima, Takumu Hasebe, Katsuya Ikuta, Katsunori Sasaki, Yoshihiro Torimoto, Mikihiro Fujiya, Yutaka Kohgo
  • Organizer: The liver meeting 2014
  • Place of Presentation: Boston
  • Year and Date: 2014-11-07 – 2014-11-11