In VitroPhosphorylation of Cytoskeletal Proteins in the Rat Cerebral Cortex Is Decreased by Propionic Acid

详细信息	查看全文 | 推荐本文 |

• 作者：de Mattos-Dutra ; Â ; ngela ; Sampaio de Freitas ; Marta ; Schrö ; der ; Nadja ; Foga&ccedil ; a Lisboa ; Carla Simone ; et. al.
• 刊名：Experimental Neurology
• 出版年：1997
• 期刊代码：78_00144886
• 类别：neu
• 出版时间：October, 1997
• 卷：147
• 期：2
• 页码：238-247
• 文件大小：180 K

摘要

In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in large amounts in propionic acidemia, is able to decreasein vitroincorporation of [³²P]ATP into neurofilament subunits (NF-M and NF-L) and α- and β-tubulin. Considering that the endogenous phosphorylating system associated with the cytoskeletal fraction contains cAMP-dependent protein kinase (PKA), Ca²⁺/calmodulin protein kinase II (CaMKII), and protein phosphatase 1 (PP1), we first assayed the effect of the acid on the kinase activities by using the specific activators cAMP and Ca²⁺/calmodulin or the inhibitors PKAI or KN-93 for PKA and CaMKII, respectively. Results demonstrated that the acid totally inhibited the stimulatory effect of cAMP and interfered with the inhibitory effect of PKAI. In addition, PA partially prevented the stimulatory effect of Ca²⁺/calmodulin and interfered with the effect of KN-93. In addition, we demonstrated that PA totally inhibitedin vitrodephosphorylation of neurofilament subunits and tubulins mediated by PP1 in brain slices pretreated with the acid. Taken together, these results demonstrate that PA inhibits thein vitroactivities of PKA, CaMKII, and PP1 associated with the cytoskeletal fraction of the cerebral cortex of rats. This study suggests that PA at the same concentrations found in tissues from propionic acidemic children may alter phosphorylation of cytoskeletal proteins, which may contribute to the neurological dysfunction characteristic of propionic acidemia.