激活的CTHRC1促进内皮细胞中的糖解:对新陈代谢和血管生成的影响
Barbara H Toomey1, Sarah A Mitrovic2, Maia Lindner-Liaw1
1Center for Molecular Medicine, MaineHealth Institute for Research, 81 Research Drive, Scarborough, ME 04074, United States.
Vascular pharmacology
|December 1, 2023
概括
原三环螺旋重复含有1 (CTHRC1) 需要的裂变来激活,促进细胞在组织修复和癌症期间的细胞存活的糖解. 这种机制在低氧条件下增强ATP的产生.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 在组织修复和癌症期间,CTHRC1由活性纤维细胞表达.
- 它的生物活性和激活机制尚不清楚.
- CTHRC1在血液中循环,来自骨细胞.
研究的目的:
- 为了调查CTHRC1的N端是否含有需要切割激活的propeptide.
- 确定全长CTHRC1对内皮细胞代谢和基因表达的影响.
- 在体内评估CTHRC1的生物活性.
主要方法:
- 在体外研究中,在内皮细胞上使用复合全长和切割的CTHRC1.
- 蛋白酶抑制剂测定用于研究片裂变.
- 在Cthrc1无和野生型小鼠上进行呼吸计.
- 对人类循环中CTHRC1水平的分析.
主要成果:
- 切割的CTHRC1显著促进了糖解,而全长的CTHRC1的效果较差.
- CTHRC1显著增加了与零小鼠相比的野生型小鼠的呼吸交换比率,这表明在体内增强了糖解.
- 在用CTHRC1.1治疗的内皮细胞中,关键的糖解酶被上调.
- 在人类受试者中,循环的全长和截断的CTHRC1水平各不相同.
结论:
- CTHRC1的激活涉及的裂变,增强糖解.
- CTHRC1促进ATP生产的糖解,帮助细胞在缺氧条件下生存,如组织损伤和癌症.
- 在癌症中,CTHRC1可能有助于华堡效应.
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