Loss of expression of glial fibrillary acidic protein in acute hyperammonemia
Loss of expression of glial fibrillary acidic protein in acute hyperammonemia
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DOI：
10.1016/s0197-0186(02)00037-2
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发表时间：
2002-08-01
影响因子：
4.2
通讯作者：
Butterworth, RF
中科院分区：
文献类型：
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作者：
Bélanger, M;Desjardins, P;Butterworth, RF
胶质纤维酸性蛋白(GFAP)是胶质细丝网络的主要组成部分，已有报道在体外培养的星形胶质细胞中该蛋白的表达发生了变化，以响应急性氨暴露。为探讨急性高氨血症对大鼠肝脏GFAP表达的影响，采用逆转录-聚合酶链式反应(RT-PCR)和合适的寡核苷酸引物，对断流性肝功能衰竭大鼠(门腔静脉吻合24 h后肝动脉结扎，HAL)大鼠脑组织中GFAP的表达进行了分析。用多克隆抗体免疫印迹法检测GFAP蛋白。在脑病昏迷前和昏迷期，当脑组织含水量显著增加且脑氨浓度在毫摩尔范围内(1-5 mM)时，断流导致GFAP基因表达显著减少55-68%(P<；0.01)，并伴随着GFAP蛋白的丢失。第二种胶质细丝蛋白S-100β的表达不受急性高氨血症的影响。这些发现提示GFAP在细胞体积调节中起作用，GFAP表达缺失可能参与急性高氨血症综合征脑水肿的发病机制。(C)2002爱思唯尔科学有限公司。保留所有权利。
Glial fibrillary acid protein (GFAP) is a major component of the glial filament network and alterations in expression of this protein in cultured astrocytes have been reported in response to acute ammonia exposure in vitro. In order to determine the effects of acute hyperammonemia in vivo on GFAP expression, brain extracts from rats with acute liver failure due to hepatic devascularization (portacaval anastomosis followed 24 h later by hepatic artery ligation, HAL) were analyzed for GFAP mRNA using reverse transcription-polymerase chain reaction (RT-PCR) and appropriate oligonucleotide primers. GFAP protein was assayed by immunoblotting using a polyclonal antibody. Hepatic devascularization resulted in a significant 55-68% decrease (P < 0.01) of GFAP mRNA and a concomitant loss of GFAP protein at precoma and coma stages of encephalopathy when brain water content was significantly increased and brain ammonia concentrations were in the millimolar range (1-5 mM). Expression of a second glial filament protein S-100 beta was unaffected by acute hyperammonemia. These findings suggest a role for GFAP in cell volume regulation and that loss of GFAP expression could contribute to the pathogenesis of brain edema in acute hyperammonemic syndromes. (C) 2002 Elsevier Science Ltd. All rights reserved.