Yoshimura N, Hatayama I, Sato K, Nishimura M
Department of Pathology, Hirosaki University School of Medicine, Hamamatsu, Japan.
J Intellect Disabil Res. 1993 Dec;37 ( Pt 6):561-7. doi: 10.1111/j.1365-2788.1993.tb00326.x.
To elucidate the roles played by copper-containing enzymes in the brain degeneration associated with Menkes disease, the brains of brindled mouse hemizygotes (BMs) were studied histochemically and biochemically before and after copper therapy. Light and electron microscopic histochemistry revealed that, while neuronal mitochondria in BM brains demonstrate only a weak diaminobenzidine reaction for cytochrome oxidase, these exhibit strong activity after therapy and in control mice. Biochemical assays of enzyme activity revealed only 30% of the normal level before a single subcutaneous application of 50 micrograms of CuCl2, whereas neuronal mitochondria of BMs surviving 8 months after the copper therapy displayed essentially no difference from the controls. Similar results were also gained for superoxide dismutase activity, although the reduction was less marked. The present findings provide direct support for decreased activities of copper-containing enzymes being responsible for the mitochondrial abnormalities and brain degeneration associated with Menkes disease.
为了阐明含铜酶在与门克斯病相关的脑退化中所起的作用，对斑驳小鼠半合子（BMs）的大脑在铜治疗前后进行了组织化学和生物化学研究。光镜和电镜组织化学显示，虽然BM大脑中的神经元线粒体对细胞色素氧化酶仅表现出微弱的二氨基联苯胺反应，但在治疗后以及对照小鼠中这些线粒体表现出强活性。酶活性的生化测定显示，在单次皮下注射50微克氯化铜之前，活性仅为正常水平的30%，而在铜治疗后存活8个月的BMs的神经元线粒体与对照相比基本没有差异。超氧化物歧化酶活性也得到了类似结果，尽管降低程度不太明显。目前的研究结果直接支持了含铜酶活性降低是导致与门克斯病相关的线粒体异常和脑退化的原因。
