Undie A S, Wang H Y, Friedman E
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Neurobiol Aging. 1995 Jan-Feb;16(1):19-28. doi: 10.1016/0197-4580(95)80004-b.
Phosphoinositide metabolism, phospholipase C immunoreactivity, and protein kinase C translocation were measured in brain slices of 6- and 24-month-old F-344 rats. Basal phosphoinositide labeling and accumulation of [3H]inositol phosphates were reduced in the 24-month-old rats. The cholinergic agonist, carbachol, induced lower net accumulations of inositol phosphates in striatal, hippocampal, and cortical slices of the aged rats. The dose-response curve for carbachol showed a significantly lower maximal response in the striatum of senescent rats, whereas the time course of [3H]inositol incorporation into inositol metabolites and the accumulation of free [3H]inositol in tissues from young and old animals were not different. Quantitative analyses showed marked reductions in endogenous brain levels of the phosphoinositides and in phospholipase C-beta 1 immunoreactivity, but no marked reductions in endogenous brain levels of the phosphoinositides and in phospholipase C-beta 1 immunoreactivity, but no changes in phospholipase C-gamma levels in aged animals. Moreover, basal protein kinase C activity and carbachol-mediated translocation of the enzyme were significantly reduced in the cerebral cortex of the senescent animals. These findings imply that aging is associated with alterations in the brain content, metabolism, and activity of phosphoinositide-derived second messengers in the F-344 rat brain.
在6个月和24个月大的F-344大鼠的脑片中测量了磷酸肌醇代谢、磷脂酶C免疫反应性和蛋白激酶C易位。24个月大的大鼠中，基础磷酸肌醇标记和[3H]肌醇磷酸的积累减少。胆碱能激动剂卡巴胆碱在老年大鼠的纹状体、海马体和皮质切片中诱导的肌醇磷酸净积累较低。卡巴胆碱的剂量反应曲线显示，衰老大鼠纹状体中的最大反应明显较低，而[3H]肌醇掺入肌醇代谢物的时间进程以及年轻和老年动物组织中游离[3H]肌醇的积累没有差异。定量分析显示，老年动物脑内磷酸肌醇的内源性水平和磷脂酶C-β1免疫反应性显著降低，但磷脂酶C-γ水平没有明显降低。此外，老年动物大脑皮质中的基础蛋白激酶C活性和卡巴胆碱介导的该酶易位显著降低。这些发现表明，衰老与F-344大鼠脑中磷酸肌醇衍生的第二信使的脑含量、代谢和活性改变有关。
