Eakes A T, Hymer T K, Rosenthal M J, Moss J, Katz M S
Department of Medicine, University of Texas Health Science Center, San Antonio, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):E126-32. doi: 10.1152/ajpendo.1996.270.1.E126.
beta-Adrenergic stimulation of adenylyl cyclase in rat liver increases during aging. We examined whether this increase is related to alterations in the stimulatory and inhibitory G proteins (Gs and Gi) linked to adenylyl cyclase. Levels of immunoreactive alpha- and beta-subunits of Ga and Gi in liver plasma membranes from 6-, 12-, 18-, and 24-mo-old rats were unchanged with age, as was pertussis toxin-catalyzed [32P]ADP ribosylation of Gi alpha. Cholera toxin-catalyzed [32P]ADP ribosylation of Ga alpha and Gs bioactivity, assessed as reconstitution of adenylyl cyclase activity in S49 cyc- cell membranes, increased two- to threefold between 6 and 12-18 mo, and declined by 24 mo. Recombinant ADP ribosylation factor (ARF) enhanced cholera toxin labeling of Gs alpha at all ages, yet abolished the increase in toxin labeling at 12-18 mo. Auto-ADP ribosylation of the cholera toxin A1 peptide also increased transiently with age. Alteration of Gs alpha, as reflected by increased cholera toxin labeling and Gs bioactivity, may be involved in the regulation of beta-adrenergic-responsive adenylyl cyclase in rat liver during aging. Moreover, changes in endogenous ARF levels could contribute to age differences in cholera toxin labeling of Gs alpha.
衰老过程中，大鼠肝脏中β-肾上腺素能对腺苷酸环化酶的刺激作用增强。我们研究了这种增强是否与与腺苷酸环化酶相关的刺激性和抑制性G蛋白（Gs和Gi）的改变有关。6、12、18和24月龄大鼠肝细胞膜中Ga和Gi免疫反应性α和β亚基的水平以及百日咳毒素催化的Giα的[32P]ADP核糖基化随年龄未发生变化。霍乱毒素催化的Gaα的[32P]ADP核糖基化和Gs生物活性（以S49 cyc-细胞膜中腺苷酸环化酶活性的重建来评估）在6至12 - 18月龄之间增加了两到三倍，并在24月龄时下降。重组ADP核糖基化因子（ARF）在所有年龄段均增强了霍乱毒素对Gsα的标记，但消除了12 - 18月龄时毒素标记的增加。霍乱毒素A1肽的自身ADP核糖基化也随年龄短暂增加。霍乱毒素标记增加和Gs生物活性所反映的Gsα改变可能参与了衰老过程中大鼠肝脏中β-肾上腺素能反应性腺苷酸环化酶的调节。此外，内源性ARF水平的变化可能导致Gsα霍乱毒素标记的年龄差异。
