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大鼠海马突触胞体膜 ATP 酶的功能蛋白质组学:左卡尼汀的作用及其与痴呆和抑郁症发病机制的关系。

Functional proteomics of synaptic plasma membrane ATP-ases of rat hippocampus: effect of l-acetylcarnitine and relationships with Dementia and Depression pathophysiology.

机构信息

Department of Biology and Biotechnology, Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, University of Pavia, Via Ferrata, 9-27100 Pavia, Italy.

Department of Biology and Biotechnology, Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, University of Pavia, Via Ferrata, 9-27100 Pavia, Italy.

出版信息

Eur J Pharmacol. 2015 Jun 5;756:67-74. doi: 10.1016/j.ejphar.2015.03.011. Epub 2015 Mar 19.

Abstract

Synaptic energy state and mitochondrial dysfunction are crucial factors in many brain pathologies. l-acetylcarnitine, a natural derivative of carnitine, improves brain energy metabolism, and has been proposed for the Therapy of many neurological and psychiatric diseases. The effects of the drug on the maximum rate (Vmax) of enzymatic activities related to hippocampal synaptic energy utilization were evaluated, in the perspective of its employment for Dementias and Depression Therapy. Two types of synaptic plasma membranes (SPM1 and SPM2) were isolated from the hippocampus of rats treated with l-acetylcarnitine (30 and 60mg/kg i.p., 28 days, 5 days/week). Acetylcholinesterase (AChE); Na(+), K(+), Mg(2+)-ATP-ase; ouabain-insensitive Mg(2+)-ATP-ase; Na(+), K(+)-ATP-ase; Ca(2+), Mg(2+)-ATP-ase activities were evaluated. In control animals, enzymatic activities were differently expressed in SPM1 , being the evaluated enzymatic activities higher in SPM2. Subchronic treatment with l-acetylcarnitine (i) did not modify AChE on both SPMs; (ii) increased Na(+), K(+), Mg(2+)-ATP-ase, ouabain-insensitive Mg(2+)-ATP-ase and Na(+), K(+)-ATP-ase at the dose of 30 and 60mg/kg on SPM1 and SPM2; (iii) increased Ca(2+), Mg(2+)-ATP-ase activity on both SPMs at the dose of 60mg/kg. These results have been discussed considering the pathophysiology and treatment of Dementias and Depression because, although referred to normal healthy animals, they support the notion that l-acetylcarnitine may have positive effects in these pathologies.

摘要

突触能量状态和线粒体功能障碍是许多脑部疾病的关键因素。左旋肉碱是肉碱的天然衍生物,可改善大脑能量代谢,已被提议用于治疗许多神经和精神疾病。从痴呆症和抑郁症治疗的角度,评估了药物对与海马突触能量利用相关的酶活性的最大速率(Vmax)的影响。用 l-乙酰肉碱(30 和 60mg/kg ip,28 天,每周 5 天)处理大鼠的海马体分离出两种类型的突触质膜(SPM1 和 SPM2)。评估了乙酰胆碱酯酶(AChE);Na(+),K(+),Mg(2+)-ATP-ase;哇巴因不敏感的 Mg(2+)-ATP-ase;Na(+),K(+) -ATPase;Ca(2+),Mg(2+)-ATPase 活性。在对照动物中,酶活性在 SPM1 中表达不同,评估的酶活性在 SPM2 中更高。亚慢性给予 l-乙酰肉碱(i)对两种 SPM 均不改变 AChE;(ii)增加了 30 和 60mg/kg 的 Na(+),K(+),Mg(2+)-ATP-ase、哇巴因不敏感的 Mg(2+)-ATP-ase 和 Na(+),K(+) -ATPase 在 SPM1 和 SPM2 上;(iii)在两种 SPM 上,60mg/kg 的剂量增加了 Ca(2+),Mg(2+)-ATP-ase 活性。这些结果是在考虑痴呆症和抑郁症的发病机制和治疗的情况下讨论的,因为尽管涉及正常健康动物,但它们支持 l-乙酰肉碱可能对这些病症具有积极影响的观点。

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