Rapid Eye Movement Sleep Deprivation Associated Increase in Na-K ATPase Activity in the Rat Brain is Due to Noradrenaline Induced α1-Adrenoceptor Mediated Increased α-Subunit of the Enzyme
Rapid Eye Movement Sleep Deprivation Associated Increase in Na-K ATPase Activity in the Rat Brain is Due to Noradrenaline Induced α1-Adrenoceptor Mediated Increased α-Subunit of the Enzyme
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DOI：
10.1007/s11064-015-1660-8
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发表时间：
2015-08-01
影响因子：
4.4
通讯作者：
Mallick, Birendra Nath
中科院分区：
文献类型：
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作者：
Amar, Megha;Mallick, Birendra Nath
快速眼动睡眠 (REMS) 调节 Na-K ATP 酶活性并维持大脑兴奋性。 REMS 剥夺 (REMSD) 相关的 Na-K ATP 酶活性增加是由去甲肾上腺素 (NA) 作用于大脑中的 α1-肾上腺素受体 (AR) 介导的。结果表明，NA 诱导的 Na-K ATP 酶活性增加是由于变构调节以及酶周转增加所致。虽然对前者已经进行了详细的研究，但我们对后者的认识还很欠缺，对此我们进行了研究。雄性Wistar大鼠采用经典花盆法剥夺REMS 4天；进行了适当的对照实验。在另一组中，将α1-AR拮抗剂哌唑嗪(PRZ)腹腔注射。 48小时后注射REMSD。实验结束时，通过颈脱位处死大鼠并取出大脑。从大脑中制备的突触体用于通过蛋白质印迹估计 Na-K ATP 酶活性以及酶亚基不同异构体的蛋白质表达。 REMSD 显着增加了突触体 Na-K ATP 酶活性，这是由于 α 1-、α 2- 和 α 3-亚型的表达差异增加，但不是 β 1- 和 β 2-亚型的表达差异增加。 PRZ 降低了 REMSD 诱导的 Na-K ATP 酶活性和蛋白表达的增加。我们还观察到 Na-K ATPase 亚基表达的增加并不是由于 mRNA 合成增强，这表明转录后调节的可能性。因此，研究结果表明，REMSD 相关的 Na-K ATP 酶活性增加是由于该酶的 α 亚基水平升高，并且是由 NA 作用于 α 1-AR 介导的 mRNA 稳定性诱导的。
Rapid eye movement sleep (REMS) modulates Na-K ATPase activity and maintains brain excitability. REMS deprivation (REMSD)-associated increased Na-K ATPase activity is mediated by noradrenaline (NA) acting on alpha 1-adrenoceptor (AR) in the brain. It was shown that NA-induced increased Na-K ATPase activity was due to allosteric modulation as well as increased turnover of the enzyme. Although the former has been studied in detail, our understanding on the latter was lacking, which we have studied. Male Wistar rats were REMS deprived for 4-days by classical flower-pot method; suitable control experiments were conducted. In another set, alpha 1-AR antagonist prazosin (PRZ) was i.p. injected 48 h REMSD onward. At the end of experiments rats were sacrificed by cervical dislocation and brains were removed. Synaptosomes prepared from the brains were used to estimate Na-K ATPase activity as well as protein expressions of different isoforms of the enzyme subunits using western blot. REMSD significantly increased synaptosomal Na-K ATPase activity and that was due to differential increase in the expressions of alpha 1-, alpha 2- and alpha 3-isoforms, but not that of beta 1- and beta 2-isoforms. PRZ reduced the REMSD-induced increased Na-K ATPase activity and protein expressions. We also observed that the increased Na-K ATPase subunit expression was not due to enhanced mRNA synthesis, which suggests the possibility of post-transcriptional regulation. Thus, the findings suggest that REMSD-associated increased Na-K ATPase activity is due to elevated level of alpha-subunit of the enzyme and that is induced by NA acting on alpha 1-AR mediated mRNA-stabilization.