在VSMC中,PKM2的克罗托尼化重编程糖解,从而导致表型转换
Shan-Hu Cao1,2,3, Ru-Yuan Ma1, Tong Cao1
1Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Vascular Biology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
在K305的Pyruvate kinase M2 (PKM2) 化驱动血管光滑肌细胞 (VSMC) 的代谢重编程. 这种修改增强了PKM2二分化和核转位,促进了VSMC切换和内脏增生.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 翻译后修改 (PTMs) 调节酸激酶M2 (PKM2) 活性.
- 最近在血管光滑肌细胞 (VSMC) 现型切换中发现了PKM2的克罗托尼化.
研究的目的:
- 调查PKM2在VSMC代谢重编程中的角色.
- 阐明PKM2化影响VSMC功能的机制.
主要方法:
- 利用PDGF-BB诱导的合成VSMC来研究PKM2的克罗化.
- 采用PKM2 K305突变来评估PKM2二分化和核转位的影响.
- 通过使用PKM2重组腺病毒,研究了体外VSMC表型切换和体内活体内皮质增生.
主要成果:
- 在合成的VSMC中,PKM2的crotonylation被上调,促进了核转位和Glut1和Ldha的表达.
- 克罗化促进了PKM2的二维形成,K305被确定为一个关键的克罗化位点.
- PKM2 K305突变影响了二分化和核转移,减少了糖解和VSMC切换.
结论:
- PKM2 K305的克罗化对于VSMC的代谢重编程和表型切换至关重要.
- 这种修改通过促进PKM2二分化来增强有氧糖解.
- PKM2 克罗托尼化在内脏增生症的发展中起着重要作用.
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