Clocks, Cell Cycles, Cancer, and Aging Role of the Adenylate Cyclase‐Cyclic AMP‐Phosphodiesterase Axis in Signal Transduction between Orcadian Oscillator and Cell Division Cycle a
Clocks, Cell Cycles, Cancer, and Aging Role of the Adenylate Cyclase‐Cyclic AMP‐Phosphodiesterase Axis in Signal Transduction between Orcadian Oscillator and Cell Division Cycle a
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腺苷酸环化酶-环 AMP-磷酸二酯酶轴在奥卡迪亚振荡器和细胞分裂周期之间的信号转导中的时钟、细胞周期、癌症和衰老作用
DOI：
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发表时间：
1994
影响因子：
5.2
通讯作者：
L. N. Edmunds
中科院分区：
文献类型：
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作者：
L. N. Edmunds
褪黑激素 (MEL) 是松果体的主要激素产物，是一种光神经内分泌传感器和生物起搏器，影响高等动物的季节适应（光周期现象），控制着多种生殖和免疫调节功能，可能在癌症、衰老和衰老中发挥作用。临床上，ME L 的产生不仅会随着年龄的增长而下降，'-* 而且施用 M E L 或植入来自年轻供体的松果体会延长老年小鼠的中值和绝对生存时间。此外，有许多报告（尽管相互矛盾）表明，在恒定光照或黑暗或非 24 小时光暗循环中饲养的多种生物体的寿命会发生改变（参见 Natelson 等人 a/.4）；这些环境疗法由松果体记录。 M E L 的产生和释放在体内表现出昼夜节律性，5 反映了内源性起搏器的控制和光的直接调节，h 并且在雏鸡中，即使在分散的细胞培养物中，在体外仍保持节律性和光敏性。反过来，环磷酸腺苷 (CAMP) 是大鼠和小鸡松果体中 MEL 合成和释放的关键调节剂，在后者中作用于起搏器下游的 MEL 合成系统，并与其协调（而不是通过）。同样，哺乳动物细胞分裂周期 (CDC) 的进展受 CAMP 调节，与离子钙 (Ca*+) 一起工作，这些控制在衰老和肿瘤组织中发生改变。”对昼夜节律振荡器和 CDC 的相互作用以及 CAMP 在该信号转导途径中的作用感兴趣，I* 可能对基因编程老化 i3.i4 的计时和细胞的恶性转化产生影响。 14 为此，我们深入研究了藻类鞭毛虫 Er4g/enn gracilis Klebs 中 CDC 的昼夜节律时钟控制，这是一种高度节律的系统，在生理和化学方面已得到很好的表征。 ly '~ 正式的。
Melatonin (MEL), the primary hormonal product of the pineal gland-a photoneuroendocrine transducer and biological pacemaker that effects the seasonal adaptation (photoperiodism) of higher animals-governs a variety of reproductive and immunoregulatory functions and may play a role in cancer, aging and senescence. Not only does M E L production decline clinically with age,'-* but administration of M E L o r the implantation of pineal from young donors prolongs both median and absolute survival times of older mice.' Further, there are a number of reports (although conflicting) that lifespan is altered in a variety of organisms reared in constant light or darkness, or in non-24-h light-dark cycles (see Natelson et a/.4); these environmental regimens are registered by the pineal. The production and release of M E L exhibits circadian rhythmicity in viuo,5 reflecting control by an endogenous pacemaker and direct regulation by light,h and, in the chick, remains both rhythmic and photosensitive in uitro, even in dispersed cell culture.' In turn, cyclic AMP (CAMP) is a key regulator of M E L synthesis and release in rats and chick' pineal, acting in the latter on the MEL-synthesizing system downstream from the pacemaker and in coordination with (as opposed to through) it.I0 Likewise, the progression of the mammalian cell division cycle (CDC) is regulated by CAMP, working together with ionic calcium (Ca*+), and these controls are altered in aging and neoplastic tissue." My colleagues and I are particularly interested in the interaction of the circadian oscillator and the CDC and the role of CAMP in this signal transduction pathway, I* with the possible implications for timekeeping in genetically programmed agingi3.i4 and for the malignant transformation of cells.14 To this end, we have intensively investigated circadian clock control of the CDC in the algal flagellate Er4g/enn gracilis Klebs, a highly rhythmic system that has been well characterized physiologically and b i~chemica l ly . '~ The formal
DOI：
10.1073/pnas.79.2.660
发表时间：
1982
影响因子：
11.1
作者：
A. Eskin;G. Corrent;C. -. Lin;D. McAdoo
通讯作者：
A. Eskin;G. Corrent;C. -. Lin;D. McAdoo