Pérez-Baun J C, Galve I, Ruiz-Verdú A, Haro A, Guillén A
Departamento de Bioquímica y Biología Molecular I, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain.
Neuropharmacology. 1994 May;33(5):641-6. doi: 10.1016/0028-3908(94)90169-4.
The loss of the ability in signalling transduction constitutes an attractive hypothesis to explain the age-related loss of functions in the nervous system. In this paper we have examined adenylyl cyclase and G proteins in Ceratitis capitata brain during aging. The intermediate level of complexity of the Mediterranean fruit fly and its short lifespan make it a particularly interesting system for aging studies. Adenylyl cyclase basal activity decreased in the course of aging. By contrast, neither guanine nucleotide-induced activation of adenylyl cyclase nor Gs protein levels were modified. However, adenylyl cyclase activation by octopamine, which is a major neurotransmitter, neuromodulator and neurohormone in insects, was lost during aging. This observation correlated with a decrease in octopamine binding to brain plasma membranes that was due to a decrease in both receptor affinity and binding sites. On the other hand, we observed an increase in the expression of C. capitata Go protein with age, as revealed by pertussis toxin-catalysed ADP-ribosylation and immunoblotting experiments, that was not correlated with an increase in beta subunit levels. This report constitutes the first direct evidence for the participation of a Go protein in aging in the nervous system.
信号转导能力的丧失构成了一个有吸引力的假说,用以解释与年龄相关的神经系统功能丧失。在本文中,我们研究了地中海实蝇大脑在衰老过程中的腺苷酸环化酶和G蛋白。地中海实蝇中等程度的复杂性水平及其较短的寿命使其成为衰老研究中一个特别有趣的系统。腺苷酸环化酶的基础活性在衰老过程中下降。相比之下,鸟嘌呤核苷酸诱导的腺苷酸环化酶激活以及Gs蛋白水平均未改变。然而,章鱼胺(昆虫体内一种主要的神经递质、神经调质和神经激素)对腺苷酸环化酶的激活作用在衰老过程中丧失。这一观察结果与章鱼胺与脑细胞膜结合的减少相关,而这种减少是由于受体亲和力和结合位点的降低所致。另一方面,通过百日咳毒素催化的ADP核糖基化和免疫印迹实验发现,随着年龄增长,地中海实蝇Go蛋白的表达增加,且这一增加与β亚基水平的增加无关。本报告构成了Go蛋白参与神经系统衰老的首个直接证据。