Expression of aspartoacylase activity in cultured rat macroglial cells is limited to oligodendrocytes

Expression of aspartoacylase activity in cultured rat macroglial cells is limited to oligodendrocytes
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DOI:
10.1385/jmn:13:1-2:47
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发表时间:
1999-08-01
影响因子:
3.1
通讯作者:
Hungund, BL
Hungund, BL
中科院分区:
医学4区
文献类型:
--
作者:
Baslow, MH;Suckow, RF;Hungund, BL

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N-乙酰-L-天冬氨酸(NAA)是脊椎动物脑和眼内重要的渗透物质,其循环代谢在两个独立的室中完成。在脑中,NAA主要在神经元中合成,并且在其调节释放之后,NAA被存在于神经胶质相关隔室中的N-乙酰化酶水解。然而,这种水解隔室的确切性质仍然不清楚。已经提出,在中枢神经系统(CNS)中,N-乙酰基转移酶的一个作用是作为分子水泵(MWP)的一部分,其使用NAA隔室间循环来逆着水梯度去除神经细胞代谢水,并且少突胶质细胞包括该代谢序列中的第二隔室。Canavan病(CD)是一种罕见的早发性遗传性海绵状脑白质营养不良,其乙酰化酶活性缺失与CNS水肿、髓鞘内肿胀和少突胶质细胞进行性丢失有关。为了进一步评估MWP假说及其与CD病因学的可能关系,将从新生大鼠脑中获得的少突胶质细胞和星形胶质细胞在培养物中生长,并检测是否存在β-酰化酶活性。这项研究的结果表明,第一次,乙酰化酶活性只在少突胶质细胞中表达。这一观察的意义,在理解的NAA代谢循环的功能进行了讨论。
N-acetyl-L-aspartate (NAA) is an important osmolyte in the vertebrate brain and eye, and its cyclical metabolism is accomplished in two separate compartments. In the brain, NAA is synthesized primarily in neurons, and after its regulated release, NAA is hydrolyzed by aspartoacylase, which is present in a glial-associated compartment. However, the precise nature of this hydrolytic compartment has remained obscure. It has been proposed that one role of aspartoacylase in the central nervous system (CNS) is as part of a molecular water pump (MWP) that uses the NAA intercompartmental cycle to remove nerve cell metabolic water against a water gradient and that oligodendrocytes comprise the second compartment in this metabolic sequence. The absence of aspartoacylase activity in Canavan disease (CD), a rare early onset genetic spongiform leukodystrophy, is associated with CNS edema, intramyelinic swelling and a progressive loss of oligdendrocytes. In order to evaluate the MWP hypothesis and its possible relationship to the etiology of CD further, both oligodendrocytes and astrocytes obtained from neonatal rat brain were grown in culture and tested for the presence of aspartoacylase activity. The results of this study show for the first time that aspartoacylase activity is expressed only in oligodendrocytes. The meaning of this observation in understanding the function of the NAA metabolic cycle is discussed.