Turner Bradley J, Lopes Elizabeth C, Cheema Surindar S
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Melbourne, Victoria 3010, Australia.
Neurosci Lett. 2003 Oct 23;350(2):132-6. doi: 10.1016/s0304-3940(03)00893-0.
Superoxide dismutase 1 (SOD1) aggregates are a histological and biochemical correlate of disease progression in neural tissues from mutant SOD1-linked forms of familial amyotrophic lateral sclerosis (FALS). In the present study, we assayed the monomeric and high molecular weight mutant SOD1 content of nervous, muscle and visceral tissues from transgenic SOD1(G93A) mice using immunoblotting and zymograms. A progressive age-dependent increase in mutant SOD1 level, aggregation and stabilisation by cross-species heterodimers was determined in lumbar spinal cord, sciatic nerve and gastrocnemius muscle. Such biochemical abnormalities were not present in cervical spinal cord, brainstem and diaphragm muscle, nor common to endogenous mouse SOD1. Mutant dismutase activity in general did not increase correspondingly with accumulating protein at later ages. These results suggest that peripheral targets such as hindlimb skeletal muscle and nerve accumulate mutant SOD1 aggregates and may therefore be susceptible to mutant SOD1-mediated toxicity, in addition to lower and upper motor neurons of the central nervous system in transgenic FALS mice.
超氧化物歧化酶1（SOD1）聚集体是与突变型SOD1相关的家族性肌萎缩侧索硬化症（FALS）神经组织中疾病进展的组织学和生化指标。在本研究中，我们使用免疫印迹和酶谱分析法检测了转基因SOD1（G93A）小鼠的神经、肌肉和内脏组织中单体和高分子量突变型SOD1的含量。在腰脊髓、坐骨神经和腓肠肌中，确定了突变型SOD1水平随年龄增长的渐进性增加、聚集以及跨物种异源二聚体的稳定化。这些生化异常在颈脊髓、脑干和膈肌中不存在，内源性小鼠SOD1也没有这种情况。在后期，突变型歧化酶活性一般不会随着蛋白质积累而相应增加。这些结果表明，除了转基因FALS小鼠中枢神经系统的上下运动神经元外，诸如后肢骨骼肌和神经等外周靶点会积累突变型SOD1聚集体，因此可能易受突变型SOD1介导的毒性影响。
