研究者詳細 - 豊國　伸哉

Isolation and characterization of annexin 2 pseudogene in Rattus norvegicus.

Isolation and characterization of annexin 2 pseudogene in Rattus norvegicus

Ozeki M, Hoshino S, Hiai H, Toyokuni S

GENE 289 巻 ( 1-2 ) 頁： 185 - 190 2002年5月

Ozeki M, Hoshino S, Hiai H, Toyokuni S

Gene 289 巻 ( 1-2 ) 頁： 185 - 90 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Gene

Annexin 2 is a calcium-regulated, phospholipid-binding protein present in endothelial cells, macrophages and some tumor cells. Annexin 2 is a substrate for a variety of protein kinases, and plays roles in the regulation of endocytosis, exocytosis and thrombolysis. We have determined the nucleotide sequence of a rat genomic DNA fragment that hybridized to a rat annexin 2 DNA complementary to RNA (cDNA) probe. Sequence analysis revealed that it was an intronless rat annexin 2, consisting of a start-to-stop-codon-length copy of the processed transcript. This pseudogene contained 33 point mutations and two deletion sites in the coding region as compared with the cDNA, and thus displayed typical features of a retroposon. Transitions were more frequent than transversions, and the most frequent type of mutation was G to A transition. We isolated a phage clone that contained a functional rat annexin 2 genomic fragment including coding exons 3 and 4. Polymerase chain reaction and subsequent sequence analysis revealed an intron of approximately 4 kbp at the same site as in humans and mice. Whereas the annexin 2 gene or its cDNA homologues have been detected in various species from Xenopus to humans, its pseudogene has been reported only in humans. In the present study, we demonstrated the presence of an annexin 2 pseudogene in rats. © 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/s0378-1119(02)00549-8

Isolation and characterization of annexin 2 pseudogene in Rattus norvegicus. 国際誌

Munetaka Ozeki, Shinsuke Hoshino, Hiroshi Hiai, Shinya Toyokuni

Gene 289 巻 ( 1-2 ) 頁： 185 - 90 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/S0378-1119(02)00549-8

Hepatocyte nuclear factor-1 alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter

Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, Toyokuni S, Tsuda K, Seino Y

DIABETES 51 巻 ( 5 ) 頁： 1409 - 1418 2002年5月

Inhibitory effect of a novel water-soluble vitamin E derivative on atherosclerosis in rabbits

Yoshida N, Murase H, Kunieda T, Toyokuni S, Tanaka T, Terao J, Naito Y, Tanigawa T, Yoshikawa T

ATHEROSCLEROSIS 162 巻 ( 1 ) 頁： 111 - 117 2002年5月

Protective effect of colored rice over white rice on Fenton reaction-based renal lipid peroxidation in rats. 国際誌

Shinya Toyokuni, Tomio Itani, Yasujiro Morimitsu, Kunihiko Okada, Munetaka Ozeki, Shohei Kondo, Koji Uchida, Toshihiko Osawa, Hiroshi Hiai, Toru Tashiro

Free radical research 36 巻 ( 5 ) 頁： 583 - 92 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Rice has been one of the most important grains. While polished white rice is favored, colored strains of rice, red, or black, have been maintained for religious purposes in Japan. We studied whether feeding of unpolished colored rice instead of white rice ameliorates oxidative renal tubular damage in rats induced by ferric nitrilotriacetate. Whereas renal lipid peroxidation was exacerbated in white rice-fed group in comparison with standard chow group, this exacerbation was not observed in red or black rice-fed groups. These changes were dependent on the proportion of colored rice to standard chow in the diet. Cyanidin 3-O-beta-D-glucoside was detectable neither in the serum nor kidney after one week of colored rice diet, but serum protocatechuic acid was significantly increased after black rice diet. There was a generalized decrease in the renal glutathione peroxidase activity in rice diet groups. Renal enzymatic activities of superoxide dismutase, glutathione S-transferase and NAD(P)H quinone reductase were not associated with the levels of lipid peroxidation. However, renal catalase activity was significantly increased in black rice-fed groups. These may partly explain the antioxidative effect. Furthermore, colored strains of rice are rich in proteins. Thus, our data warrants further investigation of the antioxidative effect of colored rice.

DOI： 10.1080/10715760290025960

Protective effect of colored rice over white rice on Fenton reaction-based renal lipid peroxidation in rats

Toyokuni S, Itani T, Morimitsu Y, Okada K, Ozeki M, Kondo S, Uchida K, Osawa T, Hiai H, Tashiro T

FREE RADICAL RESEARCH 36 巻 ( 5 ) 頁： 583 - 592 2002年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Research

Rice has been one of the most important grains. While polished white rice is favored, colored strains of rice, red, or black, have been maintained for religious purposes in Japan. We studied whether feeding of unpolished colored rice instead of white rice ameliorates oxidative renal tubular damage in rats induced by ferric nitrilotriacetate. Whereas renal lipid peroxidation was exacerbated in white rice-fed group in comparison with standard chow group, this exacerbation was not observed in red or black rice-fed groups. These changes were dependent on the proportion of colored rice to standard chow in the diet. Cyanidin 3-O-β-D-glucoside was detectable neither in the serum nor kidney after one week of colored rice diet, but serum protocatechuic acid was significantly increased after black rice diet. There was a generalized decrease in the renal glutathione peroxidase activity in rice diet groups. Renal enzymatic activities of superoxide dismutase, glutathione S-transferase and NAD(P)H quinone reductase were not associated with the levels of lipid peroxidation. However, renal catalase activity was significantly increased in black rice-fed groups. These may partly explain the antioxidative effect. Furthermore, colored strains of rice are rich in proteins. Thus, our data warrants further investigation of the antioxidative effect of colored rice.

DOI： 10.1080/10715760290025960

Web of Science

Inhibitory effect of a novel water-soluble vitamin E derivative on atherosclerosis in rabbits.

Yoshida N, Murase H, Kunieda T, Toyokuni S, Tanaka T, Terao J, Naito Y, Tanigawa T, Yoshikawa T

Atherosclerosis 162 巻 ( 1 ) 頁： 111 - 7 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Atherosclerosis

A novel vitamin E derivative that is freely soluble in water, 2-(α-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), was evaluated for ability to inhibit development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits or cholesterol-loaded New Zealand White rabbits. Although TMG rapidly entered the circulation blood after oral administration, the blood TMG concentration remained low, while neither TMG nor its metabolites appeared in the low-density lipoprotein (LDL) fraction. TMG did not decrease serum total cholesterol and the various lipoprotein-associated cholesterol fractions (very LDL-, or high-density lipoprotein- (HDL) cholesterol). TMG reduced the serum concentration of thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) in cholesterol-loaded rabbits but not WHHL rabbits. Nonetheless, TMG inhibited aortic atherosclerosis as effectively as probucol in both models. Our results indicate that TMG opposes progression of atherosclerosis not only by preventing oxidation of LDL, but also by presently unknown mechanisms. Even an antioxidant with no uptake by LDL apparently can inhibit development of atherosclerosis despite a very low serum concentration. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/s0021-9150(01)00702-x

Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter. 国際誌

Nobuhiro Ban, Yuichiro Yamada, Yoshimichi Someya, Kazumasa Miyawaki, Yu Ihara, Masaya Hosokawa, Shinya Toyokuni, Kinsuke Tsuda, Yutaka Seino

Diabetes 51 巻 ( 5 ) 頁： 1409 - 18 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mutations in the hepatocyte nuclear factor (HNF)-1alpha gene have been linked to subtype 3 of maturity-onset diabetes of the young (MODY), a disease characterized by a primary defect in insulin secretion. Here we show that the human GLUT2 gene is closely regulated by HNF-1alpha via sequences downstream of the transcriptional start site by interaction with transcriptional co-activator p300. The promoter region of the human GLUT2 gene was subcloned into luciferase expression plasmids that were transfected together with HNF-1alpha expression plasmid into a pancreatic beta-cell line, HIT-T15, to evaluate transcriptional activities. HNF-1alpha enhanced human GLUT2 promoter activity sixfold. Site-direct mutagenesis and footprint analyses showed that the HNF-1alpha binding site (+200 to +218) is critical in human GLUT2 gene expression. Furthermore, mammalian two-hybrid and immunoprecipitation studies revealed the transactivation domain of HNF-1alpha (amino acids 391-540) to interact with both the NH(2)-terminal region (amino acids 180-662) and the COOH-terminal region (amino acids 1,818-2,079) of p300. These findings demonstrated that HNF-1alpha binds to the 5'-untranslated region of GLUT2 and that p300 acts as a transcriptional co-activator for HNF-1alpha. In addition, these results provided new insight into the regulatory function of HNF-1alpha by suggesting a molecular basis for human GLUT2 gene expression.

Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter.

Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, Toyokuni S, Tsuda K, Seino Y

Diabetes 51 巻 ( 5 ) 頁： 1409 - 18 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Diabetes

Mutations in the hepatocyte nuclear factor (HNF)-1α gene have been linked to subtype 3 of maturity-onset diabetes of the young (MODY), a disease characterized by a primary defect in insulin secretion. Here we show that the human GLUT2 gene is closely regulated by HNF-1α via sequences downstream of the transcriptional start site by interaction with transcriptional co-activator p300. The promoter region of the human GLUT2 gene was subcloned into luciferase expression plasmids that were transfected together with HNF-1α expression plasmid into a pancreatic β-cell line, HIT-T15, to evaluate transcriptional activities. HNF-1α enhanced human GLUT2 promoter activity sixfold. Site-direct mutagenesis and footprint analyses showed that the HNF-1α binding site (+200 to +218) is critical in human GLUT2 gene expression. Furthermore, mammalian two-hybrid and immunoprecipitation studies revealed the transactivation domain of HNF-1α (amino acids 391-540) to interact with both the NH2-terminal region (amino acids 180-662) and the COOH-terminal region (amino acids 1,818-2,079) of p300. These findings demonstrated that HNF-1α binds to the 5′-untranslated region of GLUT2 and that p300 acts as a transcriptional co-activator for HNF-1α. In addition, these results provided new insight into the regulatory function of HNF-1α by suggesting a molecular basis for human GLUT2 gene expression.

DOI： 10.2337/diabetes.51.5.1409

Inhibitory effect of a novel water-soluble vitamin E derivative on atherosclerosis in rabbits. 国際誌

Norimasa Yoshida, Hironobu Murase, Tsutomu Kunieda, Shinya Toyokuni, Tomoyuki Tanaka, Junji Terao, Yuji Naito, Toru Tanigawa, Toshikazu Yoshikawa

Atherosclerosis 162 巻 ( 1 ) 頁： 111 - 7 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

A novel vitamin E derivative that is freely soluble in water, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), was evaluated for ability to inhibit development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits or cholesterol-loaded New Zealand White rabbits. Although TMG rapidly entered the circulation blood after oral administration, the blood TMG concentration remained low, while neither TMG nor its metabolites appeared in the low-density lipoprotein (LDL) fraction. TMG did not decrease serum total cholesterol and the various lipoprotein-associated cholesterol fractions (very LDL-, or high-density lipoprotein- (HDL) cholesterol). TMG reduced the serum concentration of thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) in cholesterol-loaded rabbits but not WHHL rabbits. Nonetheless, TMG inhibited aortic atherosclerosis as effectively as probucol in both models. Our results indicate that TMG opposes progression of atherosclerosis not only by preventing oxidation of LDL, but also by presently unknown mechanisms. Even an antioxidant with no uptake by LDL apparently can inhibit development of atherosclerosis despite a very low serum concentration.

DOI： 10.1016/S0021-9150(01)00702-X

Increase in oxidative stress in kidneys of diabetic Akita mice 査読有り国際誌 Open Access

Ueno Y, Horio F, Uchida K, Naito M, Nomura H, Kato Y, Tsuda T, Toyokuni S, Osawa T

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 66 巻 ( 4 ) 頁： 869 - 872 2002年4月

Increase in oxidative stress in kidneys of diabetic Akita mice. 国際誌 Open Access

Ueno Y, Horio F, Uchida K, Naito M, Nomura H, Kato Y, Tsuda T, Toyokuni S, Osawa T

Bioscience, biotechnology, and biochemistry 66 巻 ( 4 ) 頁： 869 - 72 2002年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：公益社団法人日本農芸化学会

New biomarkers for oxidative damage, were used to identify whether hyperglycemia caused oxidative stress in diabetic Akita mice. At 13 weeks of age, the tissues of these mice were obtained, and the levels of Nε-(hexanonyl)lysine (HEL) and dityrosine (DT) were measured, these being related to lipid peroxide-derived protein covalent modification and protein cross-linking. The levels of HEL and DT in the kidneys of Akita mice were significantly increased compared with the control mice without any accumulation of thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal-modified protein. Immunopositive staining was clearly observed in the kidneys of the Akita mice when using the anti-HEL antibody or anti-DT antibody. These results suggest that hyperglycemia in Akita mice induced oxidative stress and increased these markers in the kidneys. © 2002 by Japan Society for Bioscience, Biotechnology, and Agrochemistry.

DOI： 10.1271/bbb.66.869

Increase in oxidative stress in kidneys of diabetic Akita mice 査読有り国際誌 Open Access

Ueno Y, Horio F, Uchida K, Naito M, Nomura H, Kato Y, Tsuda T, Toyokuni S, Osawa T

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 66 巻 ( 4 ) 頁： 869 - 872 2002年4月

子宮内膜細胞診疑陽性例の検討 : 構造異型を加味した判定基準を主体に Open Access

清水恵子, 小椋聖子, 小林八郎, 豊國伸哉, 則松良明, 森谷卓也, 桜井幹己

日本臨床細胞学会雑誌 41 巻 ( 2 ) 頁： 89 - 97 2002年3月

子宮内膜細胞診疑陽性例の検討 : 構造異型を加味した判定基準を主体に Open Access

清水恵子, 小椋聖子, 小林八郎, 豊國伸哉, 則松良明, 森谷卓也, 桜井幹己

日本臨床細胞学会雑誌 41 巻 ( 2 ) 頁： 89 - 97 2002年3月

Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice. 査読有り国際誌 Open Access

Kanatsu-Shinohara M, Ogura A, Ikegawa M, Inoue K, Ogonuki N, Tashiro K, Toyokuni S, Honjo T, Shinohara T

Proceedings of the National Academy of Sciences of the United States of America 99 巻 ( 3 ) 頁： 1383 - 8 2002年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Proceedings of the National Academy of Sciences of the United States of America

Sertoli cells play a pivotal role in spermatogenesis through their interactions with germ cells. To set up a strategy for treating male infertility caused by Sertoli cell dysfunction, we developed a Sertoli cell gene transfer system by using an adenovirus vector, which maintained long-term transgene expression in the testes of infertile mice. Introduction of an adenovirus carrying the mouse Steel (Sl) gene into Sertoli cells restored partial spermatogenesis in infertile Steel/Steeldickie (Sl/Sld) mutant mouse testes. Although these males remained infertile, round spermatids and spermatozoa from the testes produced normal fertile offspring after intracytoplasmic injection into oocytes. None of the offspring showed evidence of germ line transmission of adenoviral DNA. Thus, we demonstrate a successful treatment for infertility by using a gene therapy vector. Therefore, adenovirus-mediated gene delivery into Sertoli cells not only provides an efficient and convenient means for studying germ cell-Sertoli cell interactions through manipulation of the germ cell microenvironment in vivo, but also is a useful method to treat male infertility resulting from a Sertoli cell defect.

DOI： 10.1073/pnas.022646399