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帕金森病中血小板线粒体呼吸链功能

Platelet mitochondrial respiratory chain function in Parkinson's disease.

作者信息

Blake C I, Spitz E, Leehey M, Hoffer B J, Boyson S J

机构信息

Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.

出版信息

Mov Disord. 1997 Jan;12(1):3-8. doi: 10.1002/mds.870120103.

Abstract

Reports on mitochondrial respiratory chain (MRC) complex I (CI) dysfunction in the substantia nigra in Parkinson's disease (PD) support the oxidative stress hypothesis in the neuropathogenesis of PD. Studies in peripheral tissue have found variable decreased CI and occasionally other complex activity suggestive of systemic impairment of MRC function in PD; however, MRC activity may be influenced by numerous variables. We conducted spectrophotometric measurements of MRC function in platelet mitochondrial preparations in 13 individuals with PD and 9 age-matched controls (CON) and have identified additional variables that may affect MRC activity. Mean CI, CIII, CIV, and citrate synthase (CS) activities were similar between PD and CON. CIII and CIV, specific and CS-corrected, activities were significantly positively correlated with CI in combined and individual group data, with the exception of CIII CS-corrected and CIV specific activities in CON and PD, respectively. CIII and CS specific activities were negatively correlated with age in CON, but varied randomly in PD. In PD, CIII specific activity was 1.4-fold higher in those with a history of environmental risk factors for PD and CIV specific activity was lower in those with a positive family history of PD [8.34 +/- 0.74 (n = 4) vs. 12.4 +/- 1.1 (SEM) min-1 mg-1; p = 0.046]. Group heterogeneity, variables affecting enzyme activity, and intrinsic properties of cells may thus contribute to conflicting data in studies of MRC function in platelets and other tissues.

摘要

关于帕金森病(PD)中黑质线粒体呼吸链(MRC)复合体I(CI)功能障碍的报告支持了PD神经发病机制中的氧化应激假说。外周组织研究发现,PD患者中CI活性存在不同程度降低,偶尔其他复合体活性也降低,提示MRC功能存在系统性损害;然而,MRC活性可能受多种变量影响。我们对13例PD患者和9例年龄匹配的对照者(CON)的血小板线粒体提取物进行了MRC功能的分光光度测量,并确定了其他可能影响MRC活性的变量。PD组和CON组之间的平均CI、CIII、CIV和柠檬酸合酶(CS)活性相似。在合并和单独分组数据中,经CS校正的CIII和CIV特异性活性与CI显著正相关,但CON组和PD组中经CS校正的CIII活性及CIV特异性活性除外。CON组中CIII和CS特异性活性与年龄呈负相关,但在PD组中随机变化。在PD组中,有PD环境危险因素病史者的CIII特异性活性高1.4倍,有PD家族史阳性者的CIV特异性活性较低[8.34±0.74(n = 4)对12.4±1.1(SEM)min-1 mg-1;p = 0.046]。因此,组间异质性、影响酶活性的变量以及细胞的内在特性可能导致血小板和其他组织中MRC功能研究数据相互矛盾。

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