纳+/K+-ATPase β1亚单元是脏中的ADP-Ribosyl Cyclase
Tae-Sik Nam1, Seong-Kyu Choe2,3, Uh-Hyun Kim1
1Department of Biochemistry, Wonkwang University, Iksan, Korea.
概括
脏中的Na,K-ATPase β1亚单元 (Atp1b1) 作为ADP-ribosyl环酶 (ARC) 起作用,产生循环ADP-ribose (cADPR). 这种酶在响应血管素II时调解信号传递.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 生理学 生理学 生理学
背景情况:
- ADP-ribosyl环酶 (ARC) 合成循环ADP-ribose (cADPR),这是调动 (Ca2+) 的关键第二信使.
- 在脏生理学中,ARC的确切身份和功能,特别是对激素刺激的反应,如血管激素II (AngII),仍然不完全理解.
研究的目的:
- 为了识别和表征ADP-ribosyl环酶 (ARC) 参与脏中的AngII介导信号传递.
- 阐明已识别的ARC在调节细胞内Ca2+水平和下游信号通路中的作用.
主要方法:
- 从老鼠脏组织中净化ARC活动.
- 生物化学试验证实了复合Atp1b1的ARC活性和cADPR产生.
- 在小鼠中细胞 (MES-13) 中对Atp1b1的基因敲除,随后进行AngII刺激和Ca2+成像.
主要成果:
- Na,K-ATPase (Atp1b1) 的β1亚单元被确定为大鼠提取物中的主要ARC.
- 再组合的Atp1b1显示出强大的ARC活性,有效地从NAD产生cADPR.
- 在MES-13细胞中抑制Atp1b1显著减弱了AngII诱导的cADPR合成和延长的Ca2+信号传递.
结论:
- 在细胞中,atp1b1作为关键的ADP-ribosyl循环酶起作用.
- Atp1b1直接参与通过cADPR生产调解AngII诱导的Ca2+信号.
- 这些发现揭示了Atp1b1在调节细胞对荷尔蒙刺激反应中的新作用.
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