Physiological Chemistry Laboratory, Department of Bioscience and Engineering, College of Systems Engineering and Sciences, Shibaura Institute of Technology , Saitama , Japan.
Free Radic Res. 2014 Jun;48(6):649-58. doi: 10.3109/10715762.2014.898295. Epub 2014 Mar 25.
Vitamin E deficiency induces neuronal dysfunction and while oxidative stress is likely to be involved in mediating this process, the detailed mechanisms remain to be elucidated. Previously, we found axonal degeneration in the hippocampal CA1 region in vitamin E-deficient mice of 6 months of age (long-term). However, 3 month-old (short-term) vitamin E-deficient mice did not exhibit axonal degeneration in same region. In order to characterize the mechanisms involved in axonal degeneration in long-term vitamin E-deficient mice, we examined changes in microtubule-related proteins. Long-term vitamin E-deficiency led to significantly increased expression of the phosphorylated form of collapsin response mediator protein (CRMP)-2 compared to short-term deficiency. It is well known that CRMP-2 plays a crucial role in the maintenance of neurite function. Similarly, long-term vitamin E-deficiency significantly decreased the expression of silent mating type information regulation (SIRT)-2 mRNA compared to short-term deficiency. SIRT-2 belongs to a family of class III histone deacetylases (HDACs) and functions in the deacetylation of tubulins. Furthermore, the expression of microtubule-associated protein light chain (MAP-LC)3-2, which is a key autophagy protein was significantly higher in the short-term vitamin E-deficiency than the long-term deficiency. These results indicate that the mechanisms of axonal injury in long-term vitamin E-deficient mice are related to dysfunction in microtubules assembly via alterations in microtubule-related proteins and autophagy.
维生素 E 缺乏可导致神经元功能障碍，氧化应激可能参与介导这一过程，但详细机制仍有待阐明。先前，我们发现 6 月龄（长期）维生素 E 缺乏小鼠的海马 CA1 区存在轴突变性。然而，3 月龄（短期）维生素 E 缺乏的小鼠在同一区域没有表现出轴突变性。为了阐明长期维生素 E 缺乏小鼠中轴突变性涉及的机制，我们检查了微管相关蛋白的变化。与短期缺乏相比，长期维生素 E 缺乏导致磷酸化形式的 collapsin 反应介质蛋白 (CRMP)-2 的表达显著增加。众所周知，CRMP-2 在维持神经突功能中起着至关重要的作用。同样，与短期缺乏相比，长期维生素 E 缺乏导致沉默交配型信息调节（SIRT）-2 mRNA 的表达显著降低。SIRT-2 属于 III 类组蛋白去乙酰化酶（HDAC）家族，其功能是对微管进行去乙酰化。此外，微管相关蛋白轻链 (MAP-LC)3-2 的表达在短期维生素 E 缺乏中明显高于长期缺乏。这些结果表明，长期维生素 E 缺乏小鼠轴突损伤的机制与微管相关蛋白和自噬的改变导致微管组装功能障碍有关。
