- 著者
- Takehiro Suzuki Hiroaki Yamaguchi Motoi Kikusato Tetsuro Matsuhashi Akihiro Matsuo Takeya Sato Yuki Oba Shun Watanabe Daichi Minaki Daisuke Saigusa Hiroko Shimbo Nobuyoshi Mori Eikan Mishima Hisato Shima Yasutoshi Akiyama Yoichi Takeuchi Akinori Yuri Koichi Kikuchi Takafumi Toyohara Chitose Suzuki Masahiro Kohzuki Jun-ichi Anzai Nariyasu Mano Shigeo Kure Teruyuki Yanagisawa Yoshihisa Tomioka Masaaki Toyomizu Sadayoshi Ito Hitoshi Osaka Ken-ichiro Hayashi Takaaki Abe
- 出版者
- 東北ジャーナル刊行会
- 雑誌
- The Tohoku Journal of Experimental Medicine (ISSN:00408727)
- 巻号頁・発行日
- vol.236, no.3, pp.225-232, 2015 (Released:2015-06-26)
- 参考文献数
- 27
- 被引用文献数
- 2 34
Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, indole-3-acetic acid. Importantly, MA-5 improved the survival of fibroblasts established from patients with mitochondrial diseases under the stress-induced condition, including Leigh syndrome, MELAS (myopathy encephalopathy lactic acidosis and stroke-like episodes), Leber’s hereditary optic neuropathy, and Kearns-Sayre syndrome. The improved survival was associated with the increased cellular ATP levels. Moreover, MA-5 increased the survival of mitochondrial disease fibroblasts even under the inhibition of the oxidative phosphorylation or the electron transport chain. These data suggest that MA-5 could be a therapeutic drug for mitochondrial diseases that exerts its effect in a manner different from anti-oxidant therapy.
- 著者
- KYOKO MASUKAWA YOSHIRO NISHIO KEN-ICHIRO HAYASHI
- 出版者
- GEOCHEMICAL SOCIETY OF JAPAN
- 雑誌
- GEOCHEMICAL JOURNAL (ISSN:00167002)
- 巻号頁・発行日
- vol.47, no.3, pp.309-319, 2013-06-20 (Released:2013-11-26)
- 参考文献数
- 43
- 被引用文献数
- 10
Ore-forming fluid trapped in vein quartz as fluid inclusions from tungsten ore at the Takatori mine was extracted by a crush-leach technique. The trace metal content and isotopic composition (δ7Li and 87Sr/86Sr ratio) of inclusion fluids were measured. Although quartz single crystals can host fluid inclusions associated with different generations, careful selection of analytical samples made it possible to separate the temporal mineralization stages. We succeeded in reconstructing the evolution of the ore-forming fluid from the results of chemical analyses. δ7Li values of the ore-forming fluid were between -2.6 and +7.9‰, gradually increasing in the later stages. The early-stage fluid characterized by low δ7Li values was derived from magma with a meta-sedimentary source (S-type granite). During precipitation of Li-bearing minerals, the δ7Li value of the ore-forming fluid became larger. The initial 87Sr/86Sr ratio of early-stage ore-forming fluid was 0.7202 to 0.7276, suggesting that the fluid responsible for tungsten mineralization was derived from S-type magma, and this magma had a different origin from the granitic rocks widely distributed in the mining area.