环孢素 A 全身注射对大鼠海马 PKC 底物 MARCKS 和 GAP43 磷酸化的影响。
The effect of systemic injection of cyclosporin A on the phosphorylation of the PKC substrates MARCKS and GAP43 in the rat hippocampus.
机构信息
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
出版信息
Neurosci Lett. 2011 Jun 15;497(1):17-21. doi: 10.1016/j.neulet.2011.04.012. Epub 2011 Apr 14.
Cyclosporin A (CsA) is an inhibitor of calcineurin, a calcium/calmodulin dependent serine/threonine phosphatase. Protein kinase C (PKC) is a family of serine/threonine kinases. Both calcineurin and PKC are implicated in psychiatric diseases and the therapeutic mechanisms of treatment agents. It has been reported that calcineurin interacts with components of PKC signaling pathways. We administrated 50mg/kg CsA into rats by intraperitoneal injection and examined the acute effect of single systemic CsA on the locomotor activity of rats and the phosphorylation of PKC and its substrates GAP43 and MARCKS. Systemic CsA increased locomotor activity beginning 1h after injection. The immunoreactivity of p-MARCKS(S152/156) was higher in the CsA group 1h after injection, whereas p-GAP43(S41) immunoreactivity was increased by CsA after 5h. The immunoreactivity of p-PKC pan was increased by CsA at both 1 and 5h after administration. Our data suggest that activation of the PKC pathway might be related to CsA-induced hyperlocomotion.
环孢素 A（CsA）是钙调神经磷酸酶的抑制剂，钙调神经磷酸酶是一种钙/钙调蛋白依赖性丝氨酸/苏氨酸磷酸酶。蛋白激酶 C（PKC）是丝氨酸/苏氨酸激酶家族。钙调神经磷酸酶和 PKC 都与精神疾病和治疗药物的治疗机制有关。据报道，钙调神经磷酸酶与 PKC 信号通路的成分相互作用。我们通过腹腔注射向大鼠给予 50mg/kg 的 CsA，并检查单次全身 CsA 对大鼠运动活动和 PKC 及其底物 GAP43 和 MARCKS 的磷酸化的急性影响。全身 CsA 在注射后 1 小时开始增加运动活动。注射后 1 小时，CsA 组的 p-MARCKS（S152/156）免疫反应性更高，而 CsA 可在 5 小时后增加 p-GAP43（S41）免疫反应性。CsA 在给药后 1 和 5 小时均增加了 p-PKC 泛素的免疫反应性。我们的数据表明，PKC 途径的激活可能与 CsA 诱导的过度活跃有关。
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