- 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
- Yuri Sasaki Eikan Mishima Koichi Kikuchi Takafumi Toyohara Takehiro Suzuki Hideki Ota Kazumasa Seiji Mariko Miyazaki Hideo Harigae Sadayoshi Ito Kei Takase Takaaki Abe
- 出版者
- The Japanese Society of Internal Medicine
- 雑誌
- Internal Medicine (ISSN:09182918)
- 巻号頁・発行日
- pp.5290-20, (Released:2020-08-22)
- 参考文献数
- 27
- 被引用文献数
- 3
Angioplasty for cases of chronic total occlusion of renal artery with/without atrophic kidney is generally not recommended. We here report a 57-year-old man who presented with renin-mediated refractory hypertension caused by occlusion of a unilateral renal artery leading to kidney atrophy (length: 69 mm). Angioplasty favorably achieved blood pressure control with normalized renin secretion and enlargement of the atrophic kidney to 85 mm. Timely angioplasty can be beneficial in select patients, even with an atrophic kidney and total occlusion, especially in cases with deterioration of hypertension within six months and the presence of collateral perfusion to the affected kidney.
- 著者
- Kentaro Matsumoto Shenwei Ni Hiroyuki Arai Takashi Toyama Yoshiro Saito Takehiro Suzuki Naoshi Dohmae Kojiro Mukai Tomohiko Taguchi
- 出版者
- Japan Society for Cell Biology
- 雑誌
- Cell Structure and Function (ISSN:03867196)
- 巻号頁・発行日
- vol.48, no.1, pp.59-70, 2023 (Released:2023-02-16)
- 参考文献数
- 43
Stimulator of interferon genes (STING) is an ER-localized transmembrane protein and the receptor for 2',3'-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), which is a second messenger produced by cGAMP synthase (cGAS), a cytosolic double-stranded DNA sensor. The cGAS-STING pathway plays a critical role in the innate immune response to infection of a variety of DNA pathogens through the induction of the type I interferons. Pharmacological activation of STING is a promising therapeutic strategy for cancer, thus the development of potent and selective STING agonists has been pursued. Here we report that mouse STING can be activated by phenylarsine oxide (PAO), a membrane permeable trivalent arsenic compound that preferentially reacts with thiol group of cysteine residue (Cys). The activation of STING with PAO does not require cGAS or cGAMP. Mass spectrometric analysis of the peptides generated by trypsin and chymotrypsin digestion of STING identifies several PAO adducts, suggesting that PAO covalently binds to STING. Screening of STING variants with single Cys to serine residues (Ser) reveals that Cys88 and Cys291 are critical to the response to PAO. STING activation with PAO, as with cGAMP, requires the ER-to-Golgi traffic and palmitoylation of STING. Our results identify a non-nucleotide STING agonist that does not target the cGAMP-binding pocket, and demonstrate that Cys of STING can be a novel target for the development of STING agonist.Key words: STING agonist, cysteine modification, innate immunity, phenylarsine oxide
- 著者
- Eikan Mishima Hideki Ota Takehiro Suzuki Takafumi Toyohara Kazumasa Seiji Sadayoshi Ito Yoshikatsu Saiki Kei Takase Takaaki Abe
- 出版者
- The Japanese Society of Internal Medicine
- 雑誌
- Internal Medicine (ISSN:09182918)
- 巻号頁・発行日
- pp.3855-19, (Released:2020-01-17)
- 参考文献数
- 21
We report a case in which diffusion-weighted magnetic resonance imaging (DWI) demonstrated renal artery stenosis-related renal ischemia and the therapeutic efficacy of revascularization. The patient was a 73-year-old man, who underwent descending thoracic aortic replacement due to DeBakey IIIb chronic aortic dissection, and who showed progressive renal dysfunction due to right renal artery stenosis caused by false lumen thrombosis. DWI demonstrated a decreased apparent diffusion coefficient (ADC) in the right kidney, indicating renal ischemia. Angioplasty with stenting restored renal perfusion and improved the renal function, resulting in the normalization of the decreased ADC in the treated kidney. Thus, DWI can be used to monitor renal ischemia in cases involving advanced renal artery stenosis.
- 著者
- Kentaro Matsumoto Shenwei Ni Hiroyuki Arai Takashi Toyama Yoshiro Saito Takehiro Suzuki Naoshi Dohmae Kojiro Mukai Tomohiko Taguchi
- 出版者
- Japan Society for Cell Biology
- 雑誌
- Cell Structure and Function (ISSN:03867196)
- 巻号頁・発行日
- pp.22085, (Released:2022-12-28)
Stimulator of interferon genes (STING) is an ER-localized transmembrane protein and the receptor for 2’,3’-cyclic guanosine monophosphate&endash;adenosine monophosphate (cGAMP), which is a second messenger produced by cGAMP synthase (cGAS), a cytosolic double-stranded DNA sensor. The cGAS-STING pathway plays a critical role in the innate immune response to infection of a variety of DNA pathogens through the induction of the type I interferons. Pharmacological activation of STING is a promising therapeutic strategy for cancer, thus the development of potent and selective STING agonists has been pursued. Here we report that mouse STING can be activated by phenylarsine oxide (PAO), a membrane permeable trivalent arsenic compound that preferentially reacts with thiol group of cysteine residue (Cys). The activation of STING with PAO does not require cGAS or cGAMP. Mass spectrometric analysis of the peptides generated by trypsin and chymotrypsin digestion of STING identifies several PAO adducts, suggesting that PAO covalently binds to STING. Screening of STING variants with single Cys to serine residues (Ser) reveals that Cys88 and Cys291 are critical to the response to PAO. STING activation with PAO, as with cGAMP, requires the ER-to-Golgi traffic and palmitoylation of STING. Our results identify a non-nucleotide STING agonist that does not target the cGAMP-binding pocket, and demonstrate that Cys of STING can be a novel target for the development of STING agonist.Key words: STING agonist, cysteine modification, innate immunity, phenylarsine oxide
- 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 16
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.