Peptidylarginine deiminase: a candidate factor in demyelinating disease
Peptidylarginine deiminase: a candidate factor in demyelinating disease
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DOI：
10.1046/j.1471-4159.2002.00834.x
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发表时间：
2002-04-01
影响因子：
4.7
通讯作者：
Wood, DD
中科院分区：
文献类型：
--
作者：
Moscarello, MA;Pritzker, L;Wood, DD
在早期的研究中，我们发现在多发性硬化症中瓜氨酸化髓鞘碱性蛋白（MBP）的相对量增加（Moscarello et al. 1994）。为了确定瓜氨酸化MBP与肽精氨酸脱亚胺酶（PAD）之间的时间关系，我们在一个自发脱髓鞘转基因小鼠模型中研究了酶活性、酶蛋白、PAD mRNA，并将PAD的量与瓜氨酸化MBP相关联。免疫槽印迹法检测的PAD蛋白和PAD RNA均升高。在分离研究中，我们发现PAD酶的增加是由于在膜组分中发现的PAD增加，而不是可溶性PAD （padi）。根据我们的数据，我们得出结论，髓磷脂相关PAD的上调是导致转基因小鼠在脱髓鞘临床或病理症状出现之前瓜氨酸化MBP增加的原因。我们假设类似的机制可能是多发性硬化症中瓜氨酸化MBP增加的原因。
In earlier studies we demonstrated that an increase in the relative amounts of citrullinated myelin basic protein (MBP) was found in multiple sclerosis (Moscarello et al. 1994). To determine the temporal relationship between the citrullinated MBP and peptidylarginine deiminase (PAD), the enzyme responsible for deiminating arginyl residues in proteins, we studied enzyme activity, enzyme protein, PAD mRNA in a spontaneously demyelinating transgenic mouse model and we correlated the amount of PAD with citrullinated MBP. Both PAD protein as measured in an immunoslot blot method and PAD RNA were elevated. In fractionation studies we showed that the increase in PAD enzyme was due to an increase in the PAD found in membrane fractions and not the soluble PAD (PADII). From our data we concluded that up-regulation of myelin-associated PAD was responsible for the increase in citrullinated MBP in our transgenic mice prior to onset of clinical or pathological signs of demyelination. We postulate that a similar mechanism may be responsible for the increase in citrullinated MBP in multiple sclerosis.