The development of diagnostic marker and therapeutic target for inherited metabolic disorders
Project/Area Number |
15K01691
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Applied health science
|
Research Institution | Teikyo University |
Principal Investigator |
Hama Kotaro 帝京大学, 薬学部, 准教授 (20534481)
|
Project Period (FY) |
2015-04-01 – 2020-03-31
|
Project Status |
Discontinued (Fiscal Year 2019)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
|
Keywords | 副腎白質ジストロフィー |
Outline of Final Research Achievements |
VLCFA are transported by ABCD1 into the peroxisome where they are degraded by β-oxidation. ABCD1 is the causative gene of X-ALD. Fatty acyl-coenzyme A (acyl-CoA) is an active form and serves as metabolic intermediates of fatty acids. Acyl-CoA is composed of both a hydrophobic fatty acyl moiety and a hydrophobic CoA joined with a thioester linkage. The intracellular pool of each acyl-CoA ester has not yet been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both wild-type and ABCD1-deficient HeLa cells. The findings of our study provide quantitative and metabolic information of each acyl-CoA species in living cells.
|
Academic Significance and Societal Importance of the Research Achievements |
副腎白質ジストロフィーの患者間では、その発症時期、症状の程度に大きな違いが存在し、治療を難しくしている。副腎白質ジストロフィーのすべての亜型では極長鎖脂肪酸が上昇しているものの、その亜型特異的な特徴は見出されていない。現在臨床上用いられている極長鎖脂肪酸の測定方法は、脂肪酸の総量を測定するものであり、生体内の存在様式は反映されない。申請者は今回、活性化状態として存在する脂肪酸、および、生体内に存在する極長鎖脂肪酸含有複合脂質を定量した。極長鎖脂肪酸含有脂質の産生代謝および輸送過程を制御することができれば、新しい創薬対象が見出される可能性があり、本研究はその基礎的な情報として重要である。
|
Report
(5 results)
Research Products
(27 results)
-
[Journal Article] Complex formation of sphingomyelin synthase 1 with glucosylceramide synthase increases sphingomyelin and decreases glucosylceramide levels2018
Author(s)
Yasuhiro Hayashi , Yoko Nemoto-Sasaki, Naoki Matsumoto, Kotaro Hama, Takashi Tanikawa, Saori Oka, Tadaaki Saeki, Tatsuya Kumasaka, Takanori Koizumi, Seisuke Arai, Ikuo Wada, Kazuaki Yokoyama, Takayuki Sugiura, and Atsushi Yamashita
-
Journal Title
Journal of Biological Chemistry
Volume: 293
Issue: 45
Pages: 17505-17522
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Profiling and Imaging of Phospholipids in Brains of Abcd1-Deficient Mice.2018
Author(s)
Hama K, Fujiwara Y, Morita M, Yamazaki F, Nakashima Y, Takei S, Takashima S, Setou M, Shimozawa N, Imanaka T, Yokoyama K.
-
Journal Title
Lipids
Volume: 53
Issue: 1
Pages: 85-102
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation.2016
Author(s)
Nishioka T, Arima N, Kano K, Hama K, Itai E, Yukiura H, Kise R, Inoue A, Kim SH, Solnica-Krezel L, Moolenaar WH, Chun J, Aoki J.
-
Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 23433-23433
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] LC-MS/MSによるAbcd1ノックアウトマウス脳の極長鎖脂肪酸含有リン脂質分子種の解析と糖脂質解析法の検討2016
Author(s)
笠原美那実, 笠松瞳, 豊島永莉, 前田絵里加,南佳那, 渡邉里奈, 濱弘太郎,藤原優子, 下澤伸行,守田雅志, 今中常雄,横山和明
Organizer
日本薬学会 136年会
Place of Presentation
横浜市
Year and Date
2016-03-27
Related Report
-
-
-
-
-
-