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关于CO在细胞培养中诱导HO-1表达的能力的问题:使用不同CO来源进行比较研究

Xiaoxiao Yang¹, Qiyue Mao¹, Binghe Wang¹

¹Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States.

ACS chemical biology

|February 10, 2024

概括

像CORM-2/-3这样的一氧化碳 (CO) 捐赠者不会通过CO诱导血氧酶-1 (HO-1).它们的效应是CO独立的,这突显了在将结果归因于CO信号之前需要评估捐赠机制.

科学领域:

生物化学和分子生物学
细胞信号传输细胞信号传输
药理学药理学是指药理学的学科.

背景情况:

一氧化碳 (CO) 以其内源信号和药理学作用而闻名.
化学CO捐赠物,如基于的CORM-2和CORM-3,被广泛用于研究CO机制.
一个常见的推断是,CO捐赠者可以调节血红氧酶-1 (HO-1) 表达的表达,这是一个关键的CO机制.

研究的目的:

研究CO捐赠物的作用机制,特别是CORM-2/-3和有机CO前药物.
为了确定这些捐赠者的HO-1诱导是否通过CO释放或CO独立效应进行介导.
为了比较CO气体,CORM-2/3和有机CO献体对HO-1表达和Nrf2激活的影响.

主要方法:

在RAW264.7,HeLa和HepG2细胞培养中使用CO气,CORM-2/3和有机CO供体 (BW-CO-103,BW-CO-111) 的比较研究.
在治疗后测量HO-1蛋白和mRNA表达.
在实验条件下,从捐赠者中释放的CO的评估.
Nrf2-露西法酶记者测定用于评估Nrf2激活.

主要成果:

CORM-2和CORM-3以剂量依赖的方式诱导HO-1,但不同度的CO气体没有.
在实验条件下,CORM-2/-3释放了最小的CO,表明了CO独立的HO-1诱导.
BW-CO-111,但不是BW-CO-103,剂量取决于增加HO-1水平和激活Nrf2.
单独的CO在体外没有诱导HO-1或激活Nrf2.

结论:

在CORM-2/-3和BW-CO-111中观察到的HO-1诱导不能归因于CO的释放.
这些CO捐赠者表现出CO独立的活动,可能是通过Nrf2激活.
在将观察到的生物效应归因于CO信号传递之前,必须考虑化学CO捐赠者的CO独立效应.
由于复杂性增加,体外发现可能无法直接转化为体内研究.

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