Rhythmicity of the cGMP-related signal transduction pathway in the mammalian circadian system
Rhythmicity of the cGMP-related signal transduction pathway in the mammalian circadian system
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DOI：
10.1152/ajpregu.2001.280.5.r1348
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发表时间：
2001-05-01
影响因子：
2.8
通讯作者：
Golombek, DA
中科院分区：
文献类型：
--
作者：
Ferreyra, GA;Golombek, DA
哺乳动物昼夜节律的诱导需要视交叉上核（SCN）中特定信号转导通路的激活。药理学抑制激酶如cGMP依赖性激酶（PKG）或Ca 2 +/钙调蛋白依赖性激酶，但不抑制cAMP依赖性激酶，阻断体内对光的昼夜节律响应。在这里，我们显示了仓鼠SCN中cGMP水平和PKG活性的昼夜和昼夜节律，在白天或主观日期间具有最大值。这种节律依赖于磷酸二酯酶，但不依赖于鸟苷酸环化酶的活性。5分钟的光脉冲增加了主观夜间结束时的cGMP水平[昼夜节律时间18（CT 18）]，但不是在CT13.5。蛋白质印迹分析表明PKG II亚型是SCN中存在的亚型。PKG或鸟苷酸环化酶在体内的抑制显着衰减光诱导的相移在CT 18（5分钟的光脉冲后），但不影响在SCN的c-Fos表达。这些结果表明，cGMP和PKG与SCN对光的反应有关，并经历昼夜变化。
Entrainment of mammalian circadian rhythms requires the activation of specific signal transduction pathways in the suprachiasmatic nuclei (SCN). Pharmacological inhibition of kinases such as cGMP-dependent kinase (PKG) or Ca2+/calmodulin-dependent kinase, but not cAMP-dependent kinase, blocks the circadian responses to light in vivo. Here we show a diurnal and circadian rhythm of cGMP levels and PKG activity in the hamster SCN, with maximal values during the day or subjective day. This rhythm depends on phosphodiesterase but not on guanylyl cyclase activity. Five-minute light pulses increased cGMP levels at the end of the subjective night [circadian time 18 (CT18)], but not at CT13.5. Western blot analysis indicated that the PKG II isoform is the one present in the SCN. Inhibition of PKG or guanylyl cyclase in vivo significantly attenuated light-induced phase shifts at CT18 (after 5-min light pulses) but did not affect c-Fos expression in the SCN. These results suggest that cGMP and PKG are related to SCN responses to light and undergo diurnal and circadian changes.