Funchal Cláudia, de Lima Pelaez Priscila, Loureiro Samanta Oliveira, Vivian Lilian, Dall Bello Pessutto Franciele, de Almeida Lúcia Maria Vieira, Tchernin Wofchuk Susana, Wajner Moacir, Pessoa Pureur Regina
Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Rua Ramiro Barcelos 2600 anexo, 90035-003, Porto Alegre, RS, Brazil.
Brain Res Dev Brain Res. 2002 Dec 15;139(2):267-76. doi: 10.1016/s0165-3806(02)00578-3.
In this study we investigated the effects of alpha-ketoisocaproic acid (KIC), the main keto acid accumulating in the inherited neurometabolic disorder maple syrup urine disease (MSUD), on the in vitro incorporation of 32P into intermediate filament (IF) proteins from cerebral cortex of rats during development. KIC decreased the in vitro incorporation of 32P into the IF proteins studied up to day 12, had no effect on day 15, and increased this phosphorylation in cortical slices of 17- and 21-day-old rats. A similar effect on IF phosphorylation was achieved along development by incubating cortical slices with glutamate. Furthermore, the altered phosphorylation caused by the presence of KIC in the incubation medium was mediated by the ionotropic receptors NMDA, AMPA and kainate up to day 12 and by NMDA and AMPA in tissue slices from 17- and 21-day-old rats. The results suggest that alterations of IF phosphorylation may be associated with the neuropathology of MSUD.
在本研究中，我们调查了α-酮异己酸（KIC），即遗传性神经代谢疾病枫糖尿症（MSUD）中积累的主要酮酸，对发育过程中大鼠大脑皮质中间丝（IF）蛋白体外掺入32P的影响。KIC在第12天之前降低了所研究的IF蛋白中32P的体外掺入量，在第15天没有影响，并增加了17日龄和21日龄大鼠皮质切片中的这种磷酸化。通过用谷氨酸孵育皮质切片，在发育过程中对IF磷酸化产生了类似的影响。此外，在第12天之前，孵育培养基中KIC的存在所引起的磷酸化改变是由离子型受体NMDA、AMPA和海人藻酸介导的，而在17日龄和21日龄大鼠的组织切片中是由NMDA和AMPA介导的。结果表明，IF磷酸化的改变可能与MSUD的神经病理学有关。
