甲基荷胺调节再生酶的活性,分泌和合成
Guoyong Li1, Jianchao Xu, Peili Wang
1Department of Medicine, Yale School of Medicine, New Haven, CT 06520-8029, USA.
Circulation
|February 27, 2008
概括
内源性再生酶是一种不活跃的酶,在catecholamine激增时会变得活跃,降解多余的catecholamines. 这一发现为慢性病等疾病提供了一个新的治疗点.
科学领域:
- 生物化学 生物化学
- 生理学 生理学 生理学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 雷纳是一种新型分泌的氨基氧化酶,可以代谢循环中的甲基荷胺.
- 雷纳酶的腹腔内注射降低了血压,心率和心脏收缩性.
- 在慢性病患者中观察到降低酶的血水平,但其内源性作用尚不清楚.
研究的目的:
- 调查雷纳酶在 катехо胺调节中的内源性作用.
- 了解在生理条件下再生酶的激活机制.
主要方法:
- 在活体和体外对上腺素激增的反应中评估氨酸氧化酶活性.
- 在上腺素给药后,在老鼠中测量出血动力学变化.
- 在暴露于多巴胺的培养细胞中研究再生酶基因表达.
- 在患有慢性病的老鼠中检查了prorenalase激活.
主要成果:
- 循环再生酶 (prorenalase) 基本上是不活跃的,但在上腺素激增时迅速激活.
- 激活会在几秒钟内显著增加酶活性,持续超过一个小时.
- 上腺素激增增加了血雷纳酶度,并提高了雷纳酶基因表达的调节.
- 在患有慢性脏病的老鼠中,前列纳酶激活异常.
结论:
- 发现了一种新型的甲醇胺调节机制:过多的甲醇胺激活无活性前体prorenalase,转化为活性renalase.
- 甲基荷胺激增不仅激活,而且促进再生酶的分泌和合成.
- 雷纳酶替代疗法是慢性病的有前途的治疗策略,因为它在甲基荷胺代谢中的作用.
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