New Control Mechanism for Protein Transport in Cells

细胞内蛋白质运输的新控制机制

• 批准号: 14580650
• 负责人: OGISHIMA Tadashi
• 金额: $ 2.3万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580650/
• 关键词: Outer mitochondrial membrane cytochrome b; cytochrome b_5; cytochrome P-45O_<17α>; Membrane Transport; Androgengenesis; Thetis; Purkinje cells; choroid plexus; 外膜シトクロムb5; ミトコンドリア外膜; 小胞体; 細胞内輸送; デキサメサゾン; Outer mitochondrial membrane cytochrome b; cytochrome b_5; cytochrome P-45O_<17α>; Membrane Transport; Androgengenesis; Thetis; Purkinje cells; choroid plexus; 外膜シトクロムb5; ミトコンドリア外膜; 小胞体; 細胞内輸送; デキサメサゾン

Outer mitochondrial membrane cytochrome b (OMb) was discovered in rat liver as a homologue of microsomal cytochrome b_5 (b_5). OMb was co-localized in Leydig cells with cytochrome P-450_<17α>, which catalyzes androgengenesis therein, whereas b_5 was undetectable. We have demonstrated that OMb stimulates the 17α-hydroxylase and lyase reactions of P-45O_<17α> under limited but physiological amounts of P-450 reductase, leading to an enhanced production of androstenedione from progesterone. Thus, OMband not b_5, which was believed to be responsible for the activation, was identified as a modulator for androgengenesis in rat testes. This finding prompted us to study the novel physiological functions of OMb. We analyzed the tissue localization of OMb, b_5 and P-45O_<17α> in rats by immunohistochemical staining. In the adrenal cortex OMb and b_5 were mainly present in the outer and inner portions, respectively. In the cerebellum OMb and P-450_<17α> were only detected and co-localized in the Purkinje cell, a major site for neurosteroidogenesis. In cerebrum they were co-localized in the ependymal cells of choroid plexus, which produces the cerebrospinal fluid. OMb was present also in the hippocampus and ganglionic layer. In contrast, b_5 was scarcely observed in the brain. Partially purified Purkinje cells produced testosterone from progesterone, indicating that both P-450_<17α> and 17β-hydroxysteroid dehydrogenase were active in the conversion and suggested that OMb could be responsible for stimulation of P-450_<17α>-catalyzed reactions in the cells. These results imply important functions of OMb in not only ordinary endocrine systems but also in higher life activities.

线粒体膜细胞色素B（OMB）在大鼠肝脏中被发现是微粒体细胞色素B_5（B_5）的同源物。 OMB与细胞色素p-450_<17α>共定位在Leydig细胞中，其中催化了其中的雄激素，而B_5是无法检测的。我们已经证明，在有限但物理量的P-450降低量下，OMB刺激P-45O_<17α>的17α-羟化酶和裂解酶反应，从而导致从谚语中增强了雄激素的产生。据认为，Omband不是B_5是导致激活的原因，被确定为大鼠测试中雄激素的调节剂。这一发现促使我们研究了OMB的新生理功能。我们通过免疫组织化学染色分析了大鼠中OMB，B_5和P-45O_<17α>的组织定位。在肾上腺皮质中，OMB和B_5主要存在于外部和小脑OMB中，并且P-450_<17α>仅在Purkinje细胞中被检测和共定位，Purkinje细胞是神经类固醇生成的主要部位。在大脑中，它们在脉络丛的室系室室内室中共定位，该细胞产生脑脊液。 OMB也存在于海马和神经节层中。相反，在大脑中几乎看不到B_5。部分纯化的Purkinje细胞从孕酮中产生睾丸激素，表明P-450_ <17α>和17β-羟基固醇脱氢酶均活跃，并表明OMB可以刺激P-450_ <17α>诱导细胞中的p-450_ <17α>诱导反应。这些结果意味着OMB不仅在普通的内分泌系统中，而且在更高的生活活动中的重要功能。