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 11

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
Takehiro Suzuki Masumi Yamagishi
出版者
一般社団法人 園芸学会
雑誌
The Horticulture Journal (ISSN:21890102)
巻号頁・発行日
pp.MI-089, (Released:2015-12-10)
被引用文献数
1 3

Lilium leichtlinii (2n = 2x = 24) is the most commercially cultivated edible lily in Japan, although viral and fungal diseases are severe problems. Triploid L. lancifolium (2n = 3x = 36), the bulbs of which are also edible, adapts well to the climate in Japan, and feral triploid L. lancifolium plants are often seen along roadsides and in croplands. Thus, triploid L. lancifolium is an important genetic resource for edible lilies, but it develops many bulbils (aerial bulbs) on leaf axils. Bulbil formation is undesirable for edible lilies because bulbils can compete for photosynthate with bulbs, which limits the use of triploid L. lancifolium in commercial production. Edible lily cultivars have been bred by intraspecific crosses within L. leichtlinii, although interspecific hybridization, which increases the level of genetic variation, is the major technique used to breed floricultural lily cultivars. In this study, interspecific-hybrid plants were developed by crossing triploid L. lancifolium and L. leichtlinii, and their characteristics, including bulbil formation ability, were evaluated. The crosses of triploid L. lancifolium × L. leichtlinii developed aneuploid plants, of which the chromosome number ranged from 26 to 34. Bulbil formation ability was continuously distributed in the F1 offspring, although 86% of F1 plants did not develop bulbils, indicating that many aneuploid plants without bulbils are developed by this cross combination. The plants harboring abnormal anthers were segregated in the hybrids. In addition, pollen germination in the F1 hybrids was lower than 20%, and 85% of the hybrids exhibited no pollen germination. However, abnormal anther morphology and low pollen fertility should not be major problems for edible lily production because bulbs are the main commercial output. These results indicate that interspecific hybridization between triploid L. lancifolium and L. leichtlinii has the potential to develop elite edible lily cultivars.