Grant-in-Aid for Scientific Research (B).
|Allocation Type||Single-year Grants|
Pathological medical chemistry
|Research Institution||Nagoya University|
WAKABAYASHI Takashi School of Mrdicine, Nagoya University, Professor, 医学部, 教授 (00079998)
NIKI Ichiro School of Medicine, Nagoya University, Assoc.Professor, 医学部, 助教授 (10262908)
YOSHIDA Shonen School of Medicine, Nagoya University, Professor, 医学部, 教授 (70090420)
HAYAKAWA Tetsuo School of Medicine, Nagoya University, Professor, 医学部, 教授 (80022838)
JERZY Krechn グダニスク医科系大学, 教授
ZDZISLAW Wai グダニスク医科系大学, 教授
MICHAL Wozni グダニスク医科系大学, 助教授
|Project Period (FY)
1998 – 2000
Completed(Fiscal Year 2000)
|Budget Amount *help
¥4,200,000 (Direct Cost : ¥4,200,000)
Fiscal Year 2000 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1999 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1998 : ¥1,600,000 (Direct Cost : ¥1,600,000)
|Keywords||megamitochondria / free radicals / scavengers / apoptosis / TEMPO derivatives / culture cells / 4-OH-TEMPO / 微小管 / taxol / nocodazole / acetylated α-tubulin / coenzymeQ_<10> / ミトコンドリア形態制御遺伝子 / mmml / mdm10 / スカベンジャー|
1. Establishment of the experimental model for the megamitochondria (MG) formation using culture cells.
2. Mechanism of the MG formation :
Free radicals are involved as the mechanism common to the MG formation induced by various pathologic conditions.
3. Pathophysiological meaning of the free radical-induced MG formation :
Cell in the presence of MG become apoptotic with time. MG decrease the rate of oxygen consumption thus decreasing the generation of oxygen radicals. This contributes to the suppression of the increase in the intracellular level of free radicals. If such effect do not efficiently work, cells become apoptotic.
4. Suppression of the MG formation by scavengers of free radicals : MG induced both in vivo and in vitro by various chemicals were successfully suppressed by α-tocopherol, CoQ_<10>, or 4-OH-TEMPO most effectively by 4-OH-TEMPO.
5. Synthesis of TEMPO derivatives :
4-octanoyl-and 4-lauroyl-TEMPO, among newly synthesized 6 TEMPO derivatives, have been found much more effective than 4-OH-TEMPO in suppressing the MG formation.