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一项利用从福尔马林固定、石蜡包埋材料中提取的RNA对肌萎缩侧索硬化症患者中枢神经系统中谷胱甘肽S-转移酶pi表达的研究。

A study of glutathione S-transferase pi expression in central nervous system of subjects with amyotrophic lateral sclerosis using RNA extraction from formalin-fixed, paraffin-embedded material.

作者信息

Usarek Ewa, Gajewska Beata, Kaźmierczak Beata, Kuźma Magdalena, Dziewulska Dorota, Barańczyk-Kuźma Anna

机构信息

Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097, Warsaw, Poland.

出版信息

Neurochem Res. 2005 Aug;30(8):1003-7. doi: 10.1007/s11064-005-6771-1.

Abstract

The expression of glutathione S-transferase pi (GST pi), an enzyme responsible for inactivation of a large variety of toxic compounds was studied in spinal cord, motor and sensory brain cortex obtained from patients who died in the course of amyotrophic lateral sclerosis (ALS). The studies were performed on formalin-fixed, paraffin-embedded (FFPE) and freshly frozen tissues. The method of RNA isolation from FFPE was modified. A significant decrease of GST pi-mRNA expression was found in cervical spinal cord and motor brain cortex of ALS subjects comparing to analogue control tissues (P<0.01), as well as in motor cortex of ALS subjects comparing to their sensory cortex (P<0.05). In spinal cords the decrease in GST pi-mRNA expression was accompanied by a decrease of GST pi protein level. Results indicated lowered GST pi expression on both mRNA and protein levels in the regions of nervous system affected by ALS. The non-properly inactivated by GST toxic electrophiles and organic peroxides may thus contribute to motor neurons damage.

摘要

对谷胱甘肽S-转移酶pi(GST pi)的表达进行了研究,该酶负责使多种有毒化合物失活,研究对象是取自死于肌萎缩侧索硬化症(ALS)患者的脊髓、运动性和感觉性脑皮质。研究在福尔马林固定、石蜡包埋(FFPE)和新鲜冷冻组织上进行。对从FFPE中分离RNA的方法进行了改进。与对照组织相比,在ALS患者的颈脊髓和运动性脑皮质中发现GST pi-mRNA表达显著降低(P<0.01),与感觉皮质相比,在ALS患者的运动皮质中也有降低(P<0.05)。在脊髓中,GST pi-mRNA表达的降低伴随着GST pi蛋白水平的下降。结果表明,在受ALS影响的神经系统区域,GST pi在mRNA和蛋白水平上的表达均降低。因此,未被GST正确失活的有毒亲电试剂和有机过氧化物可能导致运动神经元损伤。

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