研究者詳細 - 高橋　素子

Misc - 高橋　素子

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ラット大動脈平滑筋細胞におけるメチルグリオキサールによるヘパリン結合性EGF様増殖因子(HB-EGF)の発現誘導とその機序

車文一, 朝日通雄, 高橋素子, 金藤秀明, 東山繁樹, 谷口直之

日本分子生物学会年会プログラム・講演要旨集 19 496 - 496 1996年08月

Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines

A Okado, Y Kawasaki, Y Hasuike, M Takahashi, T Teshima, J Fujii, N Taniguchi

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS ) 225 ( 1 ) 219 - 224 1996年08月

Production of 2-oxoaldehyde compounds increases during hyperglycemic conditions and is cytotoxic to susceptible cells. We have investigated the effects of methylglyoxal and 3-deoxyglucosone at physiological concentrations on monocytic leukemia U937 cells and other cell lines. Both ladder formation of DNA and nuclear fragmentation were observed in the cells treated with these agents, indicating that apoptotic cell death was induced. The fluorescent intensity of an oxidation sensitive dye (2',7'-dichlorofluorescin) was increased in U937 cells but not in other cells in which apoptosis was not induced. The levels of intracellular glutathione, however, were only slightly changed. Apoptosis and intracellular oxidant levels were enhanced by buthionine sulfoximine, an inhibitor of glutathione biosynthesis, and partially blocked by N-acetylcysteine, an antioxidant. Thus, it is conceivable that elevation of intracellular oxidant stress is a cause of the apoptosis induced by cytotoxic 2-oxoaldehyde compounds. (C) 1996 Academic Press, Inc.

DOI PubMed CiNii

Glycation and inactivation of sorbitol dehydrogenase in normal and diabetic rats

A Hoshi, M Takahashi, J Fujii, T Myint, H Kaneto, K Suzuki, Y Yamasaki, T Kamada, N Taniguchi

BIOCHEMICAL JOURNAL ( PORTLAND PRESS ) 318 119 - 123 1996年08月

Sorbitol dehydrogenase (SDH) is involved in the polyol pathway, which plays an important role in the pathogenesis of diabetic complications. We have measured the tissue distributions of SDH mRNA, both the immunoreactive enzyme levels and the enzyme activity. SDH mRNA was especially abundant in liver, kidney and testis. Both the activity and enzyme content are high in liver and kidney but not in testis. The discrepancy between mRNA and immunoreactive enzyme levels and the activity of SDH observed in testis was also seen in livers of streptozotocin-induced diabetic rats. SDH was found to exist in both glycated and non-glycated forms, with larger amounts of the glycated protein in the diabetic liver, Moreover, after incubation of purified enzyme with glucose or fructose, its activity was markedly decreased. These results indicate that glycation causes a decrease in SDH activity in liver under diabetic conditions. The same post-transcriptional event might occur to decrease the activity of SDH in testis in normal animals.

糖尿病ラットにおけるSorbitol dehydrogenaseのグリケーションと不活性化の亢進

星歩, 高橋素子, 藤井順逸, MYINT Theingi, 谷口直之

日本分子生物学会年会プログラム・講演要旨集 19 131 - 131 1996年08月

CiNii

Deglycating enzymes from Aspergillus sp for potential application in transgenic models of diabetic complications

M Takahashi, M Pischetsrieder, VM Monnier

DIABETES ( AMER DIABETES ASSOC ) 45 812 - 812 1996年05月

研究発表ペーパー・要旨（国際会議）

Induction of aldose reductase gene expression in LEC rats during the development of the hereditary hepatitis and hepatoma

M Takahashi, A Hoshi, J Fujii, E Miyoshi, T Kasahara, K Suzuki, K Aozasa, N Taniguchi

JAPANESE JOURNAL OF CANCER RESEARCH ( JAPANESE CANCER ASSOCIATION ) 87 ( 4 ) 337 - 341 1996年04月

We examined age-related changes in the protein and the mRNA expression of aldose reductase in Livers of Long-Evans with a cinnamon-like color (LEG) rats, which develop hereditary hepatitis and hepatoma with aging, using Long-Evans with an agouti color rats as controls. The levels of the protein and mRNA of aldose reductase increased after 20 weeks, at the stage of acute hepatitis, and were maintained at 60 weeks of age, while those of aldehyde reductase seemed to be constant at all ages. The expression of aldose reductase was marked in cancerous lesions in hepatoma-bearing LEC rat liver compared to uninvolved surrounding tissues. These results indicated that elevation of aldose reductase accompanied hepatocarcinogenesis and may be related to the acquisition of immortality of the cancer cells through detoxifying cytotoxic aldehyde compounds.

FRAGMENTATION OF CERULOPLASMIN FOLLOWING NONENZYMATIC GLYCATION REACTION

KN ISLAM, M TAKAHASHI, S HIGASHIYAMA, T MYINT, N UOZUMI, Y KAYANOKI, H KANETO, H KOSAKA, N TANIGUCHI

JOURNAL OF BIOCHEMISTRY ( JAPAN BIOCHEMICAL SOC ) 118 ( 5 ) 1054 - 1060 1995年11月

Bovine ceruloplasmin underwent fragmentation following non-enzymatic glycosylation. Western blot and ELISA analyses indicated that a polyclonal rabbit antiserum to hexitollysine reacted with bovine ceruloplasmin after incubation with 0.1 M glucose, The same fragmentation was seen upon exposure of the protein to a hydrogen peroxide bolus, Both catalase and EDTA blocked peroxide-dependent fragmentation, Incubation with glucose resulted in a time-dependent release of Cu2+, The released Cu2+ appeared to participate in a Fenton-type reaction to produce hydroxyl radicals, which effected the fragmentation, Hydroxyl radical scavengers such as thiourea, mannitol, methionine, and formate inhibited this cleavage, ESR spectral studies also supported participation of hydroxyl radicals, Inhibition by EDTA of the fragmentation induced by an H2O2 bolus also supports a role for copper in a Fenton-type reaction, Taken together these results suggest that reactive oxygen species, such as superoxide anion and H2O2, were formed by the Maillard reaction which led to hydroxyl radicals being produced by a copper-dependent Fenton-type reaction, Both processes are likely to be involved in the fragmentation of ceruloplasmin.

ELEVATION OF ALDOSE REDUCTASE GENE-EXPRESSION IN RAT PRIMARY HEPATOMA AND HEPATOMA-CELL LINES - IMPLICATION IN DETOXIFICATION OF CYTOTOXIC ALDEHYDES

M TAKAHASHI, J FUJII, E MIYOSHI, A HOSHI, N TANIGUCHI

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS ) 62 ( 6 ) 749 - 754 1995年09月

Aldose reductase and aldehyde reductase are members of the aldo-keto reductase superfamily, and participate in the reduction of a wide range of carbonyl compounds. We have purified aldose reductase from rat lens and raised antiserum against it in rabbits. Immunoblot analyses using this antibody showed that a significant amount of aldose reductase was expressed in cell lines derived from hepatomas while it was negligible in normal hepatocytes. Elevated expression of aldose reductase was also observed in cancerous lesions of 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB)-induced hepatocarcinomas. Expression of aldose reductase mRNA was confirmed in these cells by Northern-blot analysis, suggesting that the induction occurred at the stage of gene transcription. The level of aldehyde reductase, however, did not change in cancerous tissue or in the cell lines. The viability of hepatoma cells in the presence of 8-deoxyglucosone and glyceraldehyde was decreased by an aldose reductase inhibitor, ONO-2235 (5-[(1Z,2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo-3- thiazolidineactic acid). Taken together, induction of aldose reductase gene expression during hepatocarcinogenesis may render cancer cells resistant to various toxic carbonyl compounds produced during metabolism or administered as anti-cancer drugs. (C) 1995 Wiley-Liss, Inc.

DOI PubMed CiNii

糖尿病の合併症-glycation glycationの中間体代謝酵素

高橋素子

細胞工学 ( (株)学研メディカル秀潤社 ) 別冊 ( 糖尿病研究ストラテジー ) 149 - 150 1995年06月

糖尿病の合併症-glycation 抗ヘキシトールリジン抗体の作製方法とウェスタンブロット法

高橋素子, Myint Theingi

細胞工学 ( (株)学研メディカル秀潤社 ) 別冊 ( 糖尿病研究ストラテジー ) 140 - 142 1995年06月

IN-VIVO GLYCATION OF ALDEHYDE REDUCTASE, A MAJOR 3-DEOXYGLUCOSONE REDUCING ENZYME - IDENTIFICATION OF GLYCATION SITES

M TAKAHASHI, YB LU, T MYINT, J FUJII, Y WADA, N TANIGUCHI

BIOCHEMISTRY ( AMER CHEMICAL SOC ) 34 ( 4 ) 1433 - 1438 1995年01月

We have reported that the enzyme which reduces 3-deoxyglucosone (3-DG), a major intermediate and a potent cross-linker in the Maillard reaction, is identical with aldehyde reductase [Takahashi, M., Fujii, J., Teshima, T., Suzuki, K., Shiba, T., and Taniguchi, N. (1993) Gene 127, 249-253]. The enzyme purified from normal rat liver was found to be partially glycated as judged by binding to a boronate column and reactivity to anti-epsilon-hexitol lysine Igc. Sites of in vivo glycation of rat Liver aldehyde reductase were identified by sequencing of digested peptides labeled with NaB[H-3](4) and by mass spectrometry. The major glycated sites were lysines 67, 84, and 140. The glycated enzyme had low catalytic efficiency (k(cat)/K-m) as compared to the nonglycated form. In streptozotocin-induced diabetic rats, the glycated form was significantly increased in kidneys. Because the enzyme plays a role in detoxifying 3-DG formed through the Maillard reaction in vivo, glycation of aldehyde reductase and reduction of its activity may result in the metabolic imbalance under diabetic conditions.

DOI PubMed CiNii

アルデヒド還元酵素の糖化と不活性化について

高橋素子

生化学 ( (公社)日本生化学会 ) 66 ( 12 ) 1570 - 1570 1994年12月

GLYCATION OF HUMAN BETA-(2)-MICROGLOBULIN IN PATIENTS WITH HEMODIALYSIS-ASSOCIATED AMYLOIDOSIS - IDENTIFICATION OF THE GLYCATED SITES

T MIYATA, R INAGI, Y WADA, Y UEDA, Y IIDA, M TAKAHASHI, N TANIGUCHI, K MAEDA

BIOCHEMISTRY ( AMER CHEMICAL SOC ) 33 ( 40 ) 12215 - 12221 1994年10月

beta(2)-Microglobulin (beta(2)M) is a major component forming amyloid deposits in patients with hemodialysis-associated amyloidosis (HAA), a serious complication of long-term hemodialysis. Recently, we demonstrated that beta(2)M modified with the Maillard reaction is a definite constituent of amyloid deposits in patients with HAA. Our further study demonstrated that this modified beta(2)M induces not only chemotaxis of monocytes but also secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 from macrophages, suggesting the potential link of glycation of beta(2)M by the Maillard reaction to the pathogenesis of HAA. The present study was undertaken to identify the glycated site(s) of beta(2)M purified from long-term hemodialysis patients as well as beta(2)M incubated with glucose in vitro. Borotritide-treated beta(2)M was cleaved by endoproteinase Lys-C, and peptides were isolated by reverse-phase high-performance liquid chromatography, followed by amino acid sequence analysis and fast atom bombardment mass spectrometry to identify the glycated site. The glycated sites of beta(2)M formed in vivo were found to be almost the same as those of glycated beta(2)M in vitro. The primary glycated site was the alpha-amino group of the amino terminal isoleucine. Other minor sites were the epsilon-amino groups of Lys-19, -41, -49, -58, -91, and -94. Computer graphics of the three-dimensional structure of beta(2)M suggested that the high specificity for the glycated site at Ile-1 may be explained by its high solvent accessibility and the nearby imidazole group of His-31 as an acid-base catalyst of the Amadori rearrangement.

DOI PubMed CiNii

肝細胞癌におけるアルド・ケト還元酵素の動態

高橋素子

日本癌学会総会記事 ( 日本癌学会 ) 53回 290 - 290 1994年10月

SELECTIVE SUPPRESSION OF IGG2A SUBCLASS IN LEC RATS DURING DEVELOPMENT

Y IKEDA, T SUGIYAMA, M TAKAHASHI, N TANIGUCHI

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS ( ELSEVIER SCIENCE BV ) 1200 ( 3 ) 277 - 280 1994年08月

The LEC rat is a mutant strain that has been established as a model of hepatitis and hepatoma. In addition to hepatic disorders, it has been found that this strain has a defect in T cell maturation, and has low levels of serum IgG. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis showed that low levels of serum IgG were largely due to reduction of the IgG2a subclass. Quantitative determination of IgG subclasses by enzyme-linked immunosorbent assay (ELISA) using subclass-specific antibodies indicated that IgG2b and IgG2c subclasses were increased during development in this strain, whereas the IgG2a subclass was markedly decreased. These results suggest that dysfunction of some helper T cells in LEC rats selectively suppress synthesis of the IgG2a subclass during development but not affect production of IgG2b and IgG2c.

アルデヒド還元酵素のグライケーションによる不活性化

高橋素子

生化学 ( (公社)日本生化学会 ) 65 ( 8 ) 902 - 902 1993年08月

糖尿病グリケーションとフリーラジカル蛋白質変性特にCu,Zn-SODの断片化と活性酸素生成

高橋素子, 谷口直之

活性酸素・フリーラジカル ( (株)メディカルレビュー社 ) 4 ( 2 ) 134 - 141 1993年03月

3-デオキシグルコソン還元酵素はアルデヒドレダクターゼと同一である

高橋素子

生化学 ( (公社)日本生化学会 ) 64 ( 9 ) 1171 - 1171 1992年09月

糖尿病の集学的管理フリーラジカルと糖尿病

谷口直之, 大河原知水, 高橋素子

綜合臨床 ( (株)永井書店 ) 41 ( 9 ) 2532 - 2535 1992年09月

3-デオキシグルコソン還元酵素とアルデヒドレダクターゼの異同についての分子生物学的考察

高橋素子

生化学 ( (公社)日本生化学会 ) 64 ( 8 ) 713 - 713 1992年08月

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