Development of specific substances evaluated by the regulation of glucose transporter involved in aging of brain

通过与大脑老化相关的葡萄糖转运蛋白的调节来评估特定物质的开发

• 批准号: 05557107
• 负责人: ISHIBASHI Sadahiko
• 金额: $ 5.63万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05557107/
• 关键词: Senescence-accelerated mouse (SAM); Glucose metabolism; Oxidative stress; Active oxygen; Peroxisome; 促進老化モデルマウス(SAM); 老化促進モデルマウス; グルコース輸送担体; サイトカラシンB

First, we tried to clarify the characteristic of the energy metabolism in the brain cells of SAMP8, a substrain of accelerated senescence-prone strain. We found that the rate of D-glucose oxidation at 4- to 8-weeks of age, just before the appearance of deficits in the brain, was higher than that in age-matched SAMR1 and SAMR2 and that the increase in glucose transporter protein in the cell surface membrane was involved in the increased metabolism. Both the increases were restricted at 4- to 8-weeks of age and the cerebral cortex.Next, we examined the involvement of oxygen free radicals in relation to the above-mentioned change in the cnergy metabolism. We found the transient increase in the contents of lipid peroxides and protein carbonyl only in the cerebral cortex of SAMP8 at 4- to 8-weeks of age in comparison with SAMR1. Accordingly, the content of hydrogen peroxide was increased in the cerebral cells of SAMP8 at 4- to 8-weeks of age. In comparison of the various enzyme activities in the peroxisome in the cerebral cortex between the two strains. The decrease in the catalase activity and increase in acyl-CoA oxidase activity were observed in SAMP8.It is quite likely that these results provide some clues towards understanding the mechanism responsible for initiating the process of senile memory impairment in the brain and contribute the development of new therapeutic substances for aging.

首先，我们试图阐明加速衰老倾向株的亚株SAMP 8的脑细胞中能量代谢的特征。我们发现，在4至8周龄的D-葡萄糖氧化率，就在出现的赤字在大脑中，是高于年龄匹配的SAMR 1和SAMR 2，并在细胞表面膜中的葡萄糖转运蛋白的增加参与代谢增加。这两种增加在4- 8周龄和大脑皮层都受到限制。接下来，我们检查了氧自由基与上述能量代谢变化的关系。我们发现，短暂的增加脂质过氧化物和蛋白质羰基的含量仅在大脑皮层的SAMP 8在4- 8周龄相比，SAMR 1。相应地，在4- 8周龄的SAMP 8的脑细胞中过氧化氢的含量增加。比较了两种菌株大脑皮层过氧化物酶体中各种酶的活性。SAMP 8中过氧化氢酶活性降低，酰基辅酶A氧化酶活性升高。这些结果可能为了解老年性记忆障碍的发病机制提供线索，并有助于开发新的抗衰老药物。

项目成果

Hideo Hasegawa: "Interactions of Ginseng extract,Ginseng separated fractions,and some triterpenoid saponins with glucose transporters in sheep erythrocytes" Planta Medica. 60. 153-157 (1994)

Hideo Hasekawa：“人参提取物、人参分离组分和一些三萜皂苷与绵羊红细胞中葡萄糖转运蛋白的相互作用”Planta Medica。

E.Sato: "Early and transient increase in oxidative stress in the cerebral cortex of senescence-accelerated mouse." Mech.Ageing Dev.86. 105-114 (1996)

E.Sato：“加速衰老小鼠大脑皮层氧化应激的早期和短暂增加。”

E. Sato: "The SAM Model of Senescence," T. Takeda Elsevier, Amsterdam, 458 (1994)

E. Sato：“衰老的 SAM 模型”，T. Takeda Elsevier，阿姆斯特丹，458 (1994)

E.Sato: "Early changes in glucose metabolism in the cerebrum of senescence accelerated mouse : involvement of glucose transporter." Brain Res.637. 133-138 (1994)

E.Sato：“小鼠大脑中葡萄糖代谢的早期变化加速了小鼠的衰老：葡萄糖转运蛋白的参与。”

Hidenori Tokuda: "Dual cffects of forskolin on glucose utilization in clutured fibroblasts,as obscrved with the use of glucose analogs" Biochem.Mol.Bol.Int.34. 653-659 (1994)

Hidenori Tokuda：“使用葡萄糖类似物观察到毛喉素对培养的成纤维细胞中葡萄糖利用的双重影响”Biochem.Mol.Bol.Int.34。