Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium.
Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium.
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DOI：
10.1371/journal.pone.0087871
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Michel T
中科院分区：
文献类型：
--
作者：
Shiroto T;Romero N;Sugiyama T;Sartoretto JL;Kalwa H;Yan Z;Shimokawa H;Michel T
小窝蛋白-1是一种与多种信号分子相互作用的支架/调节蛋白。Cavelin-1基因缺失的小鼠有明显的代谢异常，但其潜在的分子机制尚不完全清楚。我们发现氧化还原应激小鼠血浆生物标志物8-异前列腺素升高，并发现siRNA介导的血管内皮细胞小窝蛋白-1基因敲除促进细胞内过氧化氢的显著增加。小窝蛋白-1基因敲除后，内皮细胞线粒体ROS产生增加；2-脱氧-D-葡萄糖减弱了这种增加，暗示小窝蛋白-1控制糖酵解途径。我们在小窝蛋白-1基因敲除后对内皮细胞裂解产物进行了无偏见的代谢特征研究，发现细胞二肽水平显著增加(高达30倍)，与自噬激活一致。代谢分析显示，小窝蛋白-1基因敲除导致糖酵解中间产物减少，伴随着脂肪酸的增加，这表明代谢发生了变化。综上所述，这些结果表明，小窝蛋白-1在内皮细胞的氧化应激、代谢转换和自噬的调节中发挥着核心作用，并可能是心血管疾病的关键靶点。
Caveolin-1 is a scaffolding/regulatory protein that interacts with diverse signaling molecules. Caveolin-1null mice have marked metabolic abnormalities, yet the underlying molecular mechanisms are incompletely understood. We found the redox stress plasma biomarker plasma 8-isoprostane was elevated in caveolin-1null mice, and discovered that siRNA-mediated caveolin-1 knockdown in endothelial cells promoted significant increases in intracellular H2O2. Mitochondrial ROS production was increased in endothelial cells after caveolin-1 knockdown; 2-deoxy-D-glucose attenuated this increase, implicating caveolin-1 in control of glycolytic pathways. We performed unbiased metabolomic characterizations of endothelial cell lysates following caveolin-1 knockdown, and discovered strikingly increased levels (up to 30-fold) of cellular dipeptides, consistent with autophagy activation. Metabolomic analyses revealed that caveolin-1 knockdown led to a decrease in glycolytic intermediates, accompanied by an increase in fatty acids, suggesting a metabolic switch. Taken together, these results establish that caveolin-1 plays a central role in regulation of oxidative stress, metabolic switching, and autophagy in the endothelium, and may represent a critical target in cardiovascular diseases.
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影响因子：
3.7
作者：
Malinouski M;Zhou Y;Belousov VV;Hatfield DL;Gladyshev VN
通讯作者：
Gladyshev VN
影响因子：
9.2
作者：
Bosch, Marta;Mari, Montserrat;Herms, Albert;Fernandez, Ana;Fajardo, Alba;Kassan, Adam;Giralt, Albert;Colell, Anna;Balgoma, David;Barbero, Elisabet;Gonzalez-Moreno, Elena;Matias, Nuria;Tebar, Francesc;Balsinde, Jesus;Camps, Marta;Enrich, Carlos;Gross, Steven P.;Garcia-Ruiz, Carmen;Perez-Navarro, Esther;Fernandez-Checa, Jose C.;Pol, Albert
通讯作者：
Pol, Albert
DOI：
10.1042/bj20111451
发表时间：
2012-01-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Lee J;Giordano S;Zhang J
通讯作者：
Zhang J
影响因子：
4.8
作者：
Razani, B;Combs, TP;Lisanti, MP
通讯作者：
Lisanti, MP
影响因子：
37.8
作者：
Förstermann, U;Münzel, T
通讯作者：
Münzel, T