Isolation and characterization of mammalian glycerophosphodiester phosphodiesterases

哺乳动物甘油磷酸二酯磷酸二酯酶的分离和表征

• 批准号: 18580094
• 负责人: YANAKA Noriyuki
• 金额: $ 2.51万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18580094/
• 关键词: glyceronhosphodiester; glvcerophosphoinositol; skeletal muscle; atrophy; neuron; outgrowth; 筋萎縮; グリセロホスホジエステル; GDE; skeletal muscle; insulin resistance

Bacterial glycerophosphodiester phosphodiesterases are well-characterized to be periplasmic and cytosolic proteins, which play a critical role in the hydrolysis of deacylated glycerophospholipids to glycerol phosphate and alcohol. In contrast, two novel mammalian GP-PDEs, GDE1 and GDE3, were recently identified, and were shown to be involved in several physiological functions.1. A GP-PDE homolog, GDE2, was widely expressed in brain tissues including, and that the expression of GDE2 in neuroblastoma Neuro2A cells was significantly up-regulated during neuronal differentiation by retinoic acid (RA) treatment. Stable expression of GDE2 resulted in neurite formation in the absence of RA, and GDE2 accumulated at the regions of perinuclear and growth cones in Neuro2A cells. Furthermore, a loss-of-function of GDE2 in Neuro2A cells by RNAi blocked RA-induced neurite formation. These results demonstrate that GDE2 expression during neuronal differentiation plays an important role for growing neurites.2. In this study, seven mammalian GP-PDEs were virtually cloned by the approach using bioinformatics. Analysis of the hydrophobicity profile of a novel GDE, GDE7, protein indicated that two distinct hydrophobic regions are located at the N-terminus and at the C-terminus. GDE7 was expressed in mouse skin, and might be involved in the maintenance of keratinocytes.3. The predicted protein sequence of GDE5 does not contain any transmembrane sequence, suggesting that GDE5 functions as a cytosolic protein. Expression of GDE5 mRNA was shown to be regulated in skeletal muscles of fasted mice and diabetic KK-Ay mice, but its functions in skeletal muscle have remained poorly understood. In this study, I created transgenic mice specifically overexpressing GDE5 in skeletal muscle. These mice had a reduced skeletal muscle mass. Microarray analysis revealed that the expression of several genes related to cellular stress was increased in skeletal muscles of transgenic mice.

细菌甘油磷酸二酯磷酸二酯酶被充分表征为周质和胞质蛋白，它们在脱酰化甘油磷脂的水解中起关键作用至磷酸甘油和酒精。相比之下，最近发现了两个新型的哺乳动物GP-PDE，GDE1和GDE3，并被证明参与了几种生理功能。1。 GP-PDE同源物GDE2在脑组织中广泛表达，包括在神经母细胞瘤神经2a细胞中GDE2在通过视黄酸（RA）处理中神经元分化期间显着上调GDE2。 GDE2的稳定表达在不存在RA的情况下导致神经突的形成，而GDE2在神经2a细胞中积聚在核周和生长锥区域。此外，RNAi通过RNAi阻断RA诱导的神经突的形成在神经2a细胞中GDE2的功能丧失。这些结果表明，神经元分化过程中的GDE2表达对于生长神经突具有重要作用。2。在这项研究中，使用生物信息学的方法实际上克隆了七个哺乳动物的GP-PDE。对新型GDE GDE7的疏水性分析的分析表明，两个不同的疏水区位于N末端和C端。 GDE7在小鼠皮肤中表达，可能参与角质形成细胞的维持。3。 GDE5的预测蛋白质序列不包含任何跨膜序列，表明GDE5作为胞质蛋白的作用。 GDE5 mRNA的表达显示在禁食小鼠和糖尿病KK-ay小鼠的骨骼肌中受到调节，但其在骨骼肌中的功能仍然很少了解。在这项研究中，我创建了特异性过表达GDE5在骨骼肌中的转基因小鼠。这些小鼠的骨骼肌质量减少。微阵列分析表明，在转基因小鼠的骨骼肌中，与细胞应激相关的几种基因的表达增加。

项目成果

動物由来glycerophosphodiester phosphodiesteraseの網羅的探索

全面寻找动物源性甘油磷酸二酯磷酸二酯酶

• 发表时间: 2008
• 作者: 工藤尊裕;ら
• 通讯作者: ら

Overexpression of GDE5 causes skeletal muscle atrophy

GDE5过度表达导致骨骼肌萎缩

• 发表时间: 2008
• 作者: Yoshizawa;I.;et. al.
• 通讯作者: et. al.

Isolation of a novel GDE by the approach using bioinformatics

利用生物信息学方法分离新型 GDE

• 发表时间: 2008
• 作者: Kudo T.;et. al.
• 通讯作者: et. al.

骨格筋特異的GDE5過剰発現マウスは速筋型筋萎縮を呈する

过度表达骨骼肌特异性 GDE5 的小鼠表现出快肌萎缩

• 发表时间: 2008
• 作者: 吉澤郁美;ら
• 通讯作者: ら

細胞骨格を調節する新規因子GDE3の骨芽細胞分化における生理的役割

新型细胞骨架调节因子GDE3在成骨细胞分化中的生理作用

• 发表时间: 2007
• 作者: 岡崎優利;ら
• 通讯作者: ら