Busquets X, Ventayol P, Sastre M, García-Sevilla J A
Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain.
Brain Res. 1996 Feb 26;710(1-2):28-34. doi: 10.1016/0006-8993(95)01293-1.
In the postmortem human brain (20 specimens of frontal cortex, Brodmann area 9) the abundance of immunoreactive protein kinase C (PKC-alpha beta) and the activity of PKC (calcium, phosphatidylserine, and phorbol ester-dependent enzymes) were determined to study the effect of aging (range 1 month to 89 years) on this regulatory enzyme. Also, the abundance of immunoreactive G protein subunits (G alpha i1/2, G alpha i3, G alpha o, G alpha s and G beta) were assessed in parallel to investigate possible relationships with PKC-alpha beta. The abundance of PKC-alpha beta was positively correlated with aging (r = 0.62, n = 20, P < 0.005). Moreover, PKC activity also showed a significant positive correlation with the age of the subject at death (r = 0.55, n = 14, P < 0.05). Because of the known in vitro modulatory role of PKC-alpha beta on G(i) proteins, the existence of an in vivo effect of brain PKC-alpha beta on various G proteins was assessed through correlation analyses. In the brain of the same subjects, there were significant negative correlations between the immunoreactivity of PKC-alpha beta and the immunoreactivities of G alpha i1/2 (r = -0.78, n = 13, P < 0.005) and G alpha i3 (r = -0.58, n = 15, P < 0.005). In the same brains, similar negative, although non-significant, correlations were found between the levels of PKC-alpha beta and those of G alpha o, G alpha s and G beta. The results demonstrate an up-regulation of brain PKC-alpha beta with aging and suggest the existence of a relevant in vivo modulatory role of this regulatory enzyme on inhibitory Gi proteins in the human brain during the process of aging.
在人死后的大脑（20个额叶皮质标本，布罗德曼9区）中，测定了免疫反应性蛋白激酶C（PKC-αβ）的丰度和PKC（钙、磷脂酰丝氨酸和佛波酯依赖性酶）的活性，以研究衰老（范围为1个月至89岁）对这种调节酶的影响。此外，还同时评估了免疫反应性G蛋白亚基（Gαi1/2、Gαi3、Gαo、Gαs和Gβ）的丰度，以研究其与PKC-αβ的可能关系。PKC-αβ的丰度与衰老呈正相关（r = 0.62，n = 20，P < 0.005）。此外，PKC活性也与死亡时受试者的年龄呈显著正相关（r = 0.55，n = 14，P < 0.05）。由于已知PKC-αβ在体外对G(i)蛋白有调节作用，因此通过相关性分析评估了脑PKC-αβ对各种G蛋白的体内作用。在同一受试者的大脑中，PKC-αβ的免疫反应性与Gαi1/2（r = -0.78，n = 13，P < 0.005）和Gαi3（r = -0.58，n = 15，P < 0.005）的免疫反应性之间存在显著负相关。在同一大脑中，PKC-αβ水平与Gαo、Gαs和Gβ水平之间也发现了类似的负相关，尽管不显著。结果表明，随着衰老，脑PKC-αβ上调，提示该调节酶在衰老过程中对人脑中的抑制性Gi蛋白存在相关的体内调节作用。
