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Increased microglial catalase activity in multiple sclerosis grey matter

机译:多发性硬化症灰质中小胶质过氧化氢酶活性增加

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Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.
机译:慢性脱髓鞘,持续的炎症,轴突丢失和灰质神经元损伤可能是导致多发性硬化症(MS)疾病进展的病理过程。尽管尚不清楚每个过程及其病因底物的确切作用,但最近的证据表明氧化损伤是MS组织损伤的主要原因。由氧化性分子(例如活性氧(ROS))引起的组织损伤程度可通过使ROS解毒的内源性抗氧化酶来平衡。了解增强大脑抵抗MS氧化损伤的内源性机制非常重要,因为增强抗氧化反应是预防该疾病不可逆组织损伤的主要治疗策略。我们的目的是确定过氧化氢还原酶过氧化氢酶在MS灰质(GM)中的表达和活性水平。与对照GM相比,在MS GM中过氧化氢酶活性升高。我们通过免疫斑点印迹测量过氧化氢酶蛋白的表达,并通过实时聚合酶链反应(RT-PCR)测量过氧化氢酶mRNA。蛋白质分析研究表明,过氧化氢酶和小胶质细胞标记物IBA-1在MS GM中呈强正相关。另外,参照小胶质细胞特异性转录物AIF-1对过氧化氢酶mRNA水平的校准揭示了该转录物在MS中的增加。这通过MS GM中的HLA-DR免疫标记的程度来反映,其与对照GM相比显着升高。总之,这些观察提供了证据,证明小胶质过氧化氢酶活性在MS灰质中升高,并且可能是MS中重要的内源性抗氧化防御机制。

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