乳酸盐通过结合可溶性腺环酸酶来调节铁的新陈代谢
Wei Liu1, Shuping Zhang2, Quanjin Li3
1Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Cell metabolism
|July 22, 2023
概括
乳酸 (LA) 通过激活可溶性腺酸环酶 (sAC) 来增加肝素,这是一个关键的铁调节剂. 这种机制解释了运动和与疾病相关的贫血,通过将高乳糖血症与铁缺乏症联系起来.
科学领域:
- 生物化学 生物化学
- 生理学 生理学 生理学
- 分子生物学分子生物学
背景情况:
- 乳酸 (LA) 升高在运动和癌症等疾病中很常见.
- 超乳糖血症与贫血,血清铁含量低,肝素含量高有关.
- 乳酸在肝素表达中的调节作用尚不清楚.
研究的目的:
- 研究乳酸盐影响肝素表达和铁平衡的机制.
- 为了阐明将乳酸与肝素调节联系起来的分子途径.
主要方法:
- 进行了体外,体内和体内的实验.
- 研究涉及肝细胞,小鼠模型和人类受试者 (休息和运动期间).
- 分析了包括sAC,cAMP,PKA和Smad1/5/8在内的关键分子信号通路.
主要成果:
- 乳酸盐与肝细胞中的可溶性腺酸环酶 (sAC) 结合.
- 这种相互作用会增加循环腺单酸盐 (cAMP) 水平.
- 激活cAMP-PKA-Smad1/5/8通路,导致肝素转录的增加.
- 在各种条件下,这种调节轴在小鼠和人类中得到证实.
结论:
- 乳酸直接通过sAC-cAMP-PKA-Smad1/5/8通路调节肝素的表达.
- 这一发现为高乳糖血症和缺铁之间提供了一种机械联系.
- 这项研究为运动员和乳酸性酸性疾病患者观察到的贫血提供了解释.
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