单片分子氧调节血管度和炎症中的血压
Christopher P Stanley1, Ghassan J Maghzal1,2, Anita Ayer1,2
1Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Nature
|February 15, 2019
概括
哺乳动物的2,3-二氧化酶1产生单片氧 (1O2) 和酸,作为一个信号分子来调节炎症下的血压和动脉度.
科学领域:
- 生物化学
- 生理学
- 分子生物学
背景情况:
- 单片分子氧 (1O2) 在植物,细菌和真菌中已知,但不是哺乳动物.
- 氨酸二氧化酶1 (IDO1) 是一种参与底代谢的酶,在炎症期间在动脉内皮细胞中表达.
- IDO1产生的1O2及其对哺乳动物血压调节的作用以前是未知的.
研究的目的:
- 调查动脉IDO1是否产生1O2.
- 要确定IDO1产生的1O2是否影响血压的控制.
- 阐明IDO1调节血压的机制.
主要方法:
- 在过氧化的存在下检测IDO1产生的1O2的酶分析.
- 立体选择性氧化L-酸到三环氧化物.
- 在体内测试,以评估酸对血压和血管度的影响.
- 研究蛋白激酶G1α的Cys42在信号通路中的作用.
主要成果:
- 在过氧化的存在下,动脉IDO1产生1O2.
- IDO1催化L-酸的立体选择性氧化成三环氧化物.
- 在体内,酸作为内源信号分子起作用.
- 这种氧化物诱导动脉放松并降低血压,依赖于蛋白激酶G1α.
- 发现了一种新的二氧化酶活性激活.
结论:
- 哺乳动物的IDO1产生1O2和一种独特的氨基酸衍生氧化物.
- 这种机制确定了1O2在哺乳动物中的病理生理作用.
- 这些发现揭示了在炎症条件下调节血管度和血压的新途径.
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