Trypanosoma cruzi epimastigotes:: Regulation of myo-inositol transport by effectors of protein kinases A and C
Trypanosoma cruzi epimastigotes:: Regulation of myo-inositol transport by effectors of protein kinases A and C
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DOI：
10.1016/j.exppara.2007.04.011
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发表时间：
2007-10-01
影响因子：
2.1
通讯作者：
Caruso-Neves, Celso
中科院分区：
文献类型：
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作者：
Einicker-Lamas, Marcelo;Nascimento, Michelle T. C.;Caruso-Neves, Celso
肌醇是大多数克氏锥虫表面分子的前体，包括磷酸肌醇、糖基肌醇磷脂和糖基磷脂酰肌醇锚。由于寄生虫是肌醇营养缺陷型，因此肌醇转运系统可能成为新型杀锥虫药物的潜在目标，因为它的一些特性与其哺乳动物对应物不同。在这里，我们研究了 PKA 和 PKC 效应器对该运输系统的调节作用，以符合寄生虫的生理学。细胞与二丁酰环 AMP (25 μM) 或毛喉素 (30 μM) 预孵育可使肌醇摄取减少一半，这种效应可被 KT5720（PKA 抑制剂）逆转。相反，用 PMA (2.8 μg/ml) 或血清 (5%) 预孵育细胞，对肌醇的摄取有大约 50% 的刺激，而星形孢菌素 (0.5 μM) 或鞘氨醇 (10 μM) 可以逆转这种效应。这些结果使我们得出结论，克氏锥虫上鞭毛体的肌醇转运系统受 PKA 抑制并受 PKC 效应子刺激。 (c) 2007 Elsevier Inc. 保留所有权利。
Inositol is the precursor for most Trypanosoma cruzi surface molecules, including phosphoinositides, glycosylinositolphospholipids and glycosylphosphatidylinositol anchors. As the parasite is an inositol auxotroph, the inositol transport system might be a potential target for new trypanocide drugs, as some of its properties are different from its mammalian counterpart. Here, we investigated the modulation exerted by effectors of PKA and PKC on this transport system to comply with the parasite physiology. Pre-incubation of the cells with either dibutyryl-cyclic AMP (25 mu M) or forskolin (30 mu M) decreased the myo-inositol uptake by half, this effect being reversed by KT5720 (PKA inhibitor). Conversely, pre-incubation of the cells with PMA (2.8 mu g/ml) or serum (5%) had a approximate to 50% stimulation in myoinositol uptake, being this effect reversed by staurosporine (0.5 mu M) or sphingosine (10 mu M). These results allow us to conclude that the myo-inositol transport system in T cruzi epimastigotes is inhibited by PKA and stimulated by PKC effectors. (c) 2007 Elsevier Inc. All rights reserved.