MacGibbon G A, Lawlor P A, Walton M, Sirimanne E, Faull R L, Synek B, Mee E, Connor B, Dragunow M
Department of Pharmacology and Clinical Pharmacology, School of Medicine, The University of Auckland, New Zealand.
Exp Neurol. 1997 Oct;147(2):316-32. doi: 10.1006/exnr.1997.6600.
Apoptosis is an active process of cell death characterized by distinct morphological features and is often the end result of a genetic program of events, i.e., programmed cell death (PCD). There is growing evidence supporting a role for apoptosis and/or PCD in Alzheimer's disease (AD), based on DNA fragmentation studies and recent findings of increased levels of inducible transcription factors (ITFs) such as c-Jun in AD brains. We have characterized the expression of a large range of ITFs (c-Fos, Fos B, Fos-related antigens, c-Jun, Jun B, Jun D, Krox20, and Krox24) using multiple antisera in AD postmortem hippocampi and compared this with human control hippocampi as well as Huntington's disease hippocampi and human epilepsy biopsy tissue. We found little evidence of nuclear expression of any ITF except c-Jun in the human postmortem tissue, compared with nuclear staining in biopsy tissue. We found some evidence for increased levels of c-Jun and Krox24 protein and krox24 mRNA in the CA1 region of AD hippocampi, suggesting that PCD may be involved in the pathogenesis of AD. In general, staining characteristics of ITFs varied with different antisera directed against the same protein, indicating the need for caution when interpreting results.
细胞凋亡是一种以独特形态特征为特点的细胞死亡的主动过程，通常是一系列基因事件程序的最终结果，即程序性细胞死亡（PCD）。基于DNA片段化研究以及近期在阿尔茨海默病（AD）脑内发现诱导性转录因子（ITFs）如c-Jun水平升高，越来越多的证据支持细胞凋亡和/或程序性细胞死亡在AD中发挥作用。我们利用多种抗血清对AD尸检海马中多种ITFs（c-Fos、Fos B、Fos相关抗原、c-Jun、Jun B、Jun D、Krox20和Krox24）的表达进行了表征，并将其与人类对照海马、亨廷顿病海马以及人类癫痫活检组织进行了比较。与活检组织中的核染色相比，我们在人类尸检组织中几乎没有发现除c-Jun外任何ITF核表达的证据。我们发现AD海马CA1区中c-Jun和Krox24蛋白以及krox24 mRNA水平升高的一些证据，提示程序性细胞死亡可能参与AD的发病机制。一般来说，ITFs的染色特征因针对同一蛋白的不同抗血清而有所不同，这表明在解释结果时需要谨慎。
