Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle.
Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle.
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DOI：
10.1083/jcb.200505117
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发表时间：
2005-08-15
影响因子：
7.8
通讯作者：
Garcia, Celia R S
中科院分区：
文献类型：
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作者：
Beraldo, Flavio H;Almeida, Fabiana M;da Silva, Aline M;Garcia, Celia R S
宿主激素褪黑激素增加细胞质Ca 2+浓度和疟原虫细胞周期（Hotta，C.T.，M.L. Gazarini，F.H. Beraldo，F.P. Varotti，C.作者：Lopes，R. P. Pozzan和C.R.加西亚2000. 2：466-468）。在这里，我们表明，在恶性疟原虫褪黑激素诱导增加环腺苷酸（cAMP）水平和cAMP依赖性蛋白激酶（PKA）的活性（40和50%，分别）。当感染恶性疟原虫的红细胞用cAMP类似物腺苷3′，5 ′-环单磷酸N6-苯甲酰基/PKA激活剂（6-Bz-cAMP）处理时，寄生虫细胞周期发生改变。这种效应似乎取决于PKA的激活（被PKA抑制剂腺苷3′，5 ′-环硫代磷酸/8溴Rp异构体、PKI [细胞渗透肽]和H89消除）。发现cAMP和Ca 2+依赖性信号通路之间存在意想不到的串扰。褪黑素引起的cAMP增加可被磷脂酶C U 73122的阻断剂所抑制，而加入6-Bz-cAMP则通过PKA激活而增加胞浆Ca ~（2+）浓度。这些研究结果表明，在疟原虫中，一个高度复杂的相互作用之间存在的Ca 2+和cAMP信号通路，但也认为寄生虫细胞周期的褪黑激素的控制需要激活的第二信使控制的途径。
The host hormone melatonin increases cytoplasmic Ca2+ concentration and synchronizes Plasmodium cell cycle (Hotta, C.T., M.L. Gazarini, F.H. Beraldo, F.P. Varotti, C. Lopes, R.P. Markus, T. Pozzan, and C.R. Garcia. 2000. Nat. Cell Biol. 2:466–468). Here we show that in Plasmodium falciparum melatonin induces an increase in cyclic AMP (cAMP) levels and cAMP-dependent protein kinase (PKA) activity (40 and 50%, respectively). When red blood cells infected with P. falciparum are treated with cAMP analogue adenosine 3′,5′-cyclic monophosphate N6-benzoyl/PKA activator (6-Bz-cAMP) there is an alteration of the parasite cell cycle. This effect appears to depend on activation of PKA (abolished by the PKA inhibitors adenosine 3′,5′-cyclic monophosphorothioate/8 Bromo Rp isomer, PKI [cell permeable peptide], and H89). An unexpected cross talk was found to exist between the cAMP and the Ca2+-dependent signaling pathways. The increases in cAMP by melatonin are inhibited by blocker of phospholipase C U73122, and addition of 6-Bz-cAMP increases cytosolic Ca2+ concentration, through PKA activation. These findings suggest that in Plasmodium a highly complex interplay exists between the Ca2+ and cAMP signaling pathways, but also that the control of the parasite cell cycle by melatonin requires the activation of both second messenger controlled pathways.