Study of mitochondria-associated diseases by pathogenic mitochondrial DNA replication delay

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Koshikawa Nobuko 千葉県がんセンター(研究所), がん遺伝創薬研究室, 主席研究員 (90260249)
• Co-Investigator(Kenkyū-buntansha): WATANABE Takayoshi 千葉県がんセンター研究所, がん遺伝創薬研究室, 研究員 (60526060) ; NAGASE Hiroki 千葉県がんセンター研究所, がん遺伝創薬研究室, 研究所長 (90322073)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 病因性ミトコンドリアDNA / ミトコンドリア病 / PIポリアミド

Outline of Final Research Achievements

Mitochondrial DNA (mtDNA) mutation 3243 A>G is one of the causes of MELAS. We designed Pyrrole/Imidazole polyamide (PIP) in order to inhibit this gene expression (PIP2). HeLamt3243 cybrids have 3243A>G mutation, at different rates. A cybrid was treated with FITC labeled PIP2. Mitochondria were stained by FITC and were visible as dots, so were mtDNAs also stained. But FITC (equal PIP2) was eliminated from mitochondria 48 hours after treatment. In order to extend the residence time of PIP in mitochondria, triphenylphosphonium (TPP) was conjugated with fluorochrome and was introduced to the cybrid with 3243A>G mutation. Mitochondria were stained by TPP conjugated fluorochrome and kept it’s fluorescence for at least 48 hours on mitochondria. It is suggested that TPP conjugated compound reached mitochondria and remained bound for at least 48 hours post treatment. Then PIP conjugated TPP was synthesized (PIP-TPP). A cybrid with 3243 A>G mutation is being treated with PIP-TPP.

Free Research Field

腫瘍分子病理学