Protein isoaspartyl methyltransferase protects from Bax-induced apoptosis
Protein isoaspartyl methyltransferase protects from Bax-induced apoptosis
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DOI：
10.1016/s0378-1119(99)00443-6
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发表时间：
1999-11-29
期刊：
影响因子：
3.5
通讯作者：
Fürst, P
中科院分区：
文献类型：
--
作者：
Huebscher, KJ;Lee, J;Fürst, P
蛋白质L-异丙酰基甲基转移酶（Pimt）是一种高度保守的酶，其利用S-腺苷甲硫氨酸（S-adenosylmethionine，S-Met）来甲基化被年龄相关的异构化和脱酰胺化损伤的蛋白质的天冬氨酸残基。我们对这种酶特别感兴趣，因为将化合物CGP 3466加入到原代大鼠星形胶质细胞培养物中导致Pimt在mRNA水平上上调，如这里通过半定量RT-PCR所示。CGP 3466是一种与抗帕金森病药物R-（-）-丙炔苯丙胺相关的化合物，其已显示出保护免受由营养因子戒断诱导的神经细胞凋亡[Tatton et al.，1994. J. Neurochem，63，1572]。促凋亡基因Bax是停药后级联反应所必需的[Deckwerth et al.，1996. Neuron 17，401]。因此，我们研究了Pimt过表达是否能够影响原代小鼠皮层神经元中β-内酰胺酶诱导的细胞凋亡。我们的研究结果表明，Pimt确实能够保护细胞免于凋亡诱导的凋亡。此外，这种活性不限于脑特异性细胞类型，因为在COS 1细胞中也证明了相同的效果。此外，突变分析表明，保护作用是依赖于腺苷甲硫氨酸结合基序，这是很好地保守在蛋白质甲基转移酶，和突变破坏这个基序至关重要地影响细胞的细胞骨架结构。(C)1999 Elsevier Science B. V.保留所有权利。
Protein L-isoaspartyl methyltransferase (Pimt) is a highly conserved enzyme utilising S-adenosylmethionine (AdoMet) to methylate aspartate residues of proteins damaged by age-related isomerisation and deamidation. We have been particularly interested in this enzyme since addition of the compound CGP3466 to primary rat astroglia cell cultures resulted in an upregulation of Pimt at the mRNA level, as shown here by semi-quantitative RT-PCR. CGP3466 is a compound related to the anti-Parkinson's drug R-(-)-deprenyl, which has been shown to protect from neural apoptosis induced by trophic factor withdrawal [Tatton et al., 1994. J. Neurochem, 63, 1572]. The pro-apoptotic gene Bax is required in the cascade of events following withdrawal [Deckwerth et al., 1996. Neuron 17, 401]. We therefore investigated whether Pimt overexpression was able to affect Bax-induced apoptosis in primary mouse cortical neurons. Our results show that Pimt is indeed able to protect from Bax-induced apoptosis. Furthermore, this activity is not restricted to brain-specific cell types, since the same effect is also demonstrated in COS1 cells. In addition, mutational analysis suggests that the protective effect is dependent on the adenosine methionine-binding motif, which is well conserved in protein methyltransferases, and that a mutation destroying this motif crucially affects cytoskeletal structures of the cell. (C) 1999 Elsevier Science B.V. All rights reserved.