Collapse of signal transduction during aging and molecular pharmacological research regarding the control.

衰老过程中信号转导的崩溃及其控制的分子药理学研究。

• 批准号: 08838021
• 负责人: MIYAMOTO Atsushi
• 金额: $ 1.34万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08838021/
• 关键词: Aging; G proteins; G protein mRNA; Development; ddy mice; Wistar rats; Signal transduction; 学習・記憶障害; ニューロステロイド; デハイドロエピアンドロステロン; プレグネノロン; コレステロール; C57BL; 6Jマウス

Several different guanine nucleotide regulatory proteins (G proteins) have been identified and their functions explored in brain (e.g.Gsalpha increases adenylyl cyclase and Ca^<2+> channels ; Gi1alpha decreases adenylyl cyclase : Gi2alpha increases phosphatidylinositol-phospholipase C (PI-PLC) ; Gi3alpha increases K^+ channels ; Goalpha decreases Ca^<2+> channels ; Gqalpha increases PI-PLC ; Gbeta decreases adenylyl cyclase and increases PI-PLC). The expression of Gsalpha and beta-actin mRNA was determined over the same period of development by hybridization blot analysis of total mice and rat cerebral cortex RNA using oligonucleotides for probes. Three age groups (3,12 and 24 months old) of male ddy mice and three age groups (3,6 and 24 months old) od male Wistar rats were employed in this study. The mean life spans were 23.1 and 23.5 months in male ddy mice and male Wistar rats, respecively. Total RNA from cerebral cortex was isolated by the guanidinium thiocyanate/phenol/chloroform method. Yield of total RNA/tissue weight did not differ from 3 months to 24 months of age in both animals. An age-dependent increase in the levels of Gsalpha protein mRNA (1.9kb) and beta-actin mRNA (2.0kb) was observed in the mice. In contrast, the levels of Gsalpha mRNA and beta-actin mRNA were essentially identical in the rats during aging. These results indicate that the ontogeny of Gsalpha mRNA and beta-actin mRNA between mice and rats are qualitatively different during brain aging.

已确定了几种不同的鸟嘌呤核苷酸调节蛋白(G蛋白)，并对它们在脑中的功能进行了研究(例如，Gsalpha增加腺酰环化酶和钙通道；Gi1α减少腺酰环化酶：Gi2α增加磷脂酰肌醇-磷脂酶C(PI-PLC)；Gi3α增加K^+通道；GoAlpha减少Ca^&lt；2+&gt；通道；GqAlpha增加PI-PLC；Gbeta减少腺苷环化酶和PI-PLC)。以寡核苷酸为探针，通过小鼠和大鼠大脑皮层总RNA的杂交印迹分析，确定Gsalpha和β-肌动蛋白在同一发育时期的表达。选用3、12、24月龄雄性ddy小鼠和3、6、24月龄雄性Wistar大鼠。雄性ddy小鼠平均寿命为23.1个月，雄性Wistar大鼠平均寿命为23.5个月。用硫氰酸胍/酚/氯仿法提取大脑皮层总RNA。从3月龄到24月龄，两种动物的总RNA/组织重量的产量没有差异。Gsalpha蛋白mRNA(1.9kb)和β-肌动蛋白mRNA(2.0kb)水平随年龄增长而升高。相反，在衰老过程中，Gsalpha和β-肌动蛋白的mRNA水平基本相同。这些结果表明，在脑老化过程中，小鼠和大鼠Gsalpha和β-肌动蛋白mRNA的个体发育存在质的差异。

项目成果

宮本 篤: "C57BL/6J老化モデルマウスの学習・記憶障害に対するニューロステロイドの作用" 日本薬理学雑誌. 108. 139P-142P (1996)

Atsushi Miyamoto：“神经类固醇对 C57BL/6J 衰老模型小鼠学习和记忆障碍的影响”日本药理学杂志 108. 139P-142P (1996)

Nishikawa, Satoshi: "Mechanisms of ET-1 release from endothelial cells in pregnancy-induced hypertension." J.Cardiovasc.Pharmacol.31. S528-S530 (1998)

Nishikawa, Satoshi：“妊娠诱发高血压中内皮细胞释放 ET-1 的机制。”

Nishikawa, Satoshi: "The Biology of Nitric Oxide.Part 6" Portland Press(Eds.Monkada,S et al.)(in press),

Nishikawa，Satoshi：“一氧化氮生物学。第 6 部分”波特兰出版社（Eds.Monkada，S 等人）（印刷中），

Kanaya,Noriaki: "Role of L-type calcium channels on helothane-induced myocardial depression in cultured rat ventricular myocytes." Res.Commun.Mol.Pathol.Pharmacol.91. 85-96 (1996)

Kanaya，Noriaki：“L 型钙通道对培养的大鼠心室肌细胞中 Helothane 诱导的心肌抑制的作用。”

Miyamoto, Atsushi: "Molecular diversity and double regulatory mechanism of activation of phospholipase C in rat brain." Life Sci.(in press).

Miyamoto, Atsushi：“大鼠脑中磷脂酶 C 激活的分子多样性和双重调节机制。”