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硫化物氧化促进缺氧血管生成和新血管化
Roshan Kumar1, Victor Vitvitsky1, Apichaya Sethaudom1
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Nature chemical biology
|March 21, 2024
概括
低氧性上调氧化 (NO),增加硫化 (H2S) 的血管生长. 然而,阻断H2S氧化限制了这种生长,为抑制瘤血管生成提供了一个目标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 身体生理学 身体生理学
背景情况:
- 血管生成,或新的血管形成,对于组织恒温至关重要,并且在癌症等疾病中受到失调.
- 气体信号分子,包括氧化 (NO) 和硫化 (H2S),在调节内皮细胞功能的过程中起着复杂的作用.
- 连接这些气体信号分子与血管生成的代谢途径仍然不完全理解.
研究的目的:
- 研究气体信号分子调节内皮细胞内血管生成的代谢机制.
- 探索转硫路径和硫化 (H2S) 生物发生在缺氧诱导的血管生成中的作用.
- 确定硫化氨酸氧化还原酶 (SQOR) 缺乏对内皮细胞增殖和新血管化的影响.
主要方法:
- 利用低氧条件研究内皮细胞反应.
- 研究了转硫化路径和H2S生产的重编程.
- 生成并分析了全身和内皮特异性的Sqor-knockout小鼠模型 (WBCreSqorfl/fl和VE-cadherinCre-ERT2Sqorfl/fl).
- 在股骨动脉绑定后评估瘤异种移植生长和肌肉血管生成.
主要成果:
- 缺氧增加了内皮细胞中氧化 (NO) 的调节,从而通过转硫化途径增强了硫化 (H2S) 的产生.
- 缺少SQOR会损害H2S氧化,与缺氧协同作用,通过诱导还原性转移来限制内皮增殖.
- 与对照组相比,Sqor-knockout小鼠 (全身和内皮特异性) 显示瘤质量,血管生成和肌肉新血管化减少.
结论:
- 数据揭示了H2S,氧 (O2) 和NO代谢之间的关键分子联系,用于调节内皮细胞行为.
- 抑制SQOR代表了代谢的脆弱性,可以限制内皮细胞的增殖和新血管化.
- 向SQOR提供了一种潜在的治疗策略,用于抑制病理性血管生成,例如瘤.
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