Tantini B, Pignatti C, Zanfanti M L, Sacchi P, Caldarera C M, Clò C
Dipartimento di Biochimica G Moruzzi, Centro Studi e Ricerche sul Metabolismo Cardiaco, Università degli Studi, Bologna.
Cardiologia. 1992 Sep;37(9):655-8.
The metabolic and functional activity of the heart closely depends on cAMP and therefore on the integrity of adenylate cyclase (AC) system. Alterations of this signal transduction system might be co-responsible for the impairment of cardiac performance observed with aging. Evidence is here provided that basal activity of cardiac membrane-bound (48,000 x g) AC significantly declines with the age of the rat (1, 12, 24 month-old). This is accompanied with the decrease of cAMP content, which leads to the fall of cAMP/cGMP molar ratio a possible final determinant of cardiac performance. Kinetic analyses indicate that aging is associated with a net increase of the Km of a cardiac AC, while the Vmax is unaffected. Besides, the response in vitro of AC from 24-month-old heart to the inhibitor spermine or a different stimulants, such as Gpp (NH) p, isoproterenol, PGE1 or forskolin, is significantly lower than that of AC from 1 month-old one. The suggestion is made that aging causes an impairment in the capability of the catalytic moiety of cardiac AC to make functional complexes with activated guanine nucleotide binding proteins.
心脏的代谢和功能活动紧密依赖于环磷酸腺苷(cAMP),因此也依赖于腺苷酸环化酶(AC)系统的完整性。这种信号转导系统的改变可能是导致衰老过程中心脏功能受损的共同原因。本文提供的证据表明,大鼠(1、12、24月龄)心脏膜结合(48,000×g)AC的基础活性随年龄增长显著下降。这伴随着cAMP含量的降低,进而导致cAMP/cGMP摩尔比下降,而该比值可能是心脏功能的最终决定因素。动力学分析表明,衰老与心脏AC的米氏常数(Km)净增加有关,而最大反应速度(Vmax)不受影响。此外,24月龄心脏的AC对抑制剂精胺或不同刺激物(如Gpp(NH)p、异丙肾上腺素、前列腺素E1或福斯可林)的体外反应明显低于1月龄心脏的AC。有人提出,衰老会导致心脏AC催化部分与活化的鸟嘌呤核苷酸结合蛋白形成功能复合物的能力受损。