Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
Neurosci Lett. 2010 Mar 19;472(2):90-3. doi: 10.1016/j.neulet.2010.01.049. Epub 2010 Feb 6.
Normal aging is associated with chronic oxidative stress. In the basal ganglia, oxidative stress may contribute to the increased risk of Parkinson's disease in the elderly. Neurons are thought to actively utilize compensatory defense mechanisms, such as heat shock proteins (HSPs), to protect from persisting stress. Despite their protective role, little is known about HSP expression in the aging basal ganglia. The purpose of this study was to examine HSP expression in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month-old Fischer 344/Brown Norway rats. We found robust age-related increases in phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72 (the inducible form of HSP70) was reduced with age, but only in the striatum. p38 MAPK, a protein implicated in activating HSP25, did not change with age, nor did HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that HSP25 is especially responsive to age-related stress in the basal ganglia.
正常衰老与慢性氧化应激有关。在基底神经节中,氧化应激可能导致老年人帕金森病风险增加。人们认为神经元会主动利用热休克蛋白(HSPs)等补偿性防御机制来抵御持续的应激。尽管它们具有保护作用,但对于衰老基底神经节中的 HSP 表达知之甚少。本研究旨在检查 6、18 和 30 月龄 Fischer 344/布朗挪威大鼠纹状体、黑质、苍白球和皮质中的 HSP 表达。我们发现,在研究的每个脑区,磷酸化和总 HSP25 都与年龄呈强相关增加。相反,HSP72(HSP70 的诱导形式)随年龄减少,但仅在纹状体中。p38 MAPK 是一种与 HSP25 激活有关的蛋白,其随年龄变化不大,HSC70(HSP70 的组成型形式)或 HSP60 也没有变化。这些结果表明,HSP25 对基底神经节中与年龄相关的应激特别敏感。