首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Propionic and methylmalonic acids inhibit the in vitro phosphorylation of a 85 kDa cytoskeletal protein from cerebral cortex of rats.
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Propionic and methylmalonic acids inhibit the in vitro phosphorylation of a 85 kDa cytoskeletal protein from cerebral cortex of rats.

机译:丙酸和甲基丙二酸可抑制大鼠大脑皮层中85 kDa细胞骨架蛋白的体外磷酸化。

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摘要

In this study we examine the action of methylmalonic (MMA) and propionic (PA) acids, metabolites which accumulate in methylmalonic and propionic acidemias respectively, on the endogenous phosphorylating system associated with the cytoskeletal fraction of cerebral cortex of young rats. Chronic treatment with PA and treatment of tissue slices with MMA or PA are effective in decreasing the in vitro phosphorylation into a 85 kDa cytoskeletal associated protein. We tested the effect of the acids on the endogenous kinase activities by using specific kinase activators and inhibitors. Results demonstrated that the acids interfere with the endogenous cAMP-dependent and Ca2+/calmodulin-dependent kinase activities. Furthermore, in vitro dephosphorylation of the 85 kDa protein was totally inhibited in brain slices treated with the acids. Considering the importance of protein phosphorylation to cellular function, we speculate that alteration in the phosphorylating level of cytoskeletal associated phosphoproteins induced by MMA and PA treatments may somehow be involved in steps leading to brain damage.
机译:在这项研究中,我们研究了甲基丙二酸(MMA)和丙酸(PA)分别在甲基丙二酸和丙酸酸血症中积累的代谢产物对与幼鼠大脑皮质细胞骨架部分相关的内源性磷酸化系统的作用。 PA的慢性治疗和MMA或PA的组织切片治疗可有效减少体外磷酸化成85 kDa细胞骨架相关蛋白。我们通过使用特定的激酶激活剂和抑制剂测试了酸对内源性激酶活性的影响。结果表明,酸会干扰内源性cAMP依赖性和Ca2 + /钙调蛋白依赖性激酶活性。此外,在用酸处理过的脑片中,85 kDa蛋白的体外去磷酸化被完全抑制。考虑到蛋白质磷酸化对细胞功能的重要性,我们推测由MMA和PA治疗诱导的细胞骨架相关磷蛋白磷酸化水平的改变可能以某种方式参与导致脑损伤的步骤。

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