Experimental and Computational Biochemistry Group, Faculty of Sciences, Nutrition and Biochemistry Department, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Immunology and Cell Biology Group, Faculty of Sciences, Microbiology Department, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Int J Mol Sci. 2023 Feb 23;24(5):4394. doi: 10.3390/ijms24054394.
An increase in plasma high glucose promotes endothelial dysfunction mainly through increasing mitochondrial ROS production. High glucose ROS-induced has been implicated in the fragmentation of the mitochondrial network, mainly by an unbalance expression of mitochondrial fusion and fission proteins. Mitochondrial dynamics alterations affect cellular bioenergetics. Here, we assessed the effect of PDGF-C on mitochondrial dynamics and glycolytic and mitochondrial metabolism in a model of endothelial dysfunction induced by high glucose. High glucose induced a fragmented mitochondrial phenotype associated with the reduced expression of OPA1 protein, high DRP1 levels and reduced basal respiration, maximal respiration, spare respiratory capacity, non-mitochondrial oxygen consumption and ATP production, regarding normal glucose. In these conditions, PDGF-C significantly increased the expression of OPA1 fusion protein, diminished DRP1 levels and restored the mitochondrial network. On mitochondrial function, PDGF-C increased the non-mitochondrial oxygen consumption diminished by high glucose conditions. These results suggest that PDGF-C modulates the damage induced by HG on the mitochondrial network and morphology of human aortic endothelial cells; additionally, it compensates for the alteration in the energetic phenotype induced by HG.
血浆高葡萄糖水平升高主要通过增加线粒体 ROS 产生促进内皮功能障碍。高葡萄糖 ROS 诱导的线粒体网络碎片化已被牵连，主要是通过线粒体融合和分裂蛋白的不平衡表达。线粒体动力学的改变会影响细胞的生物能量学。在这里，我们评估了 PDGF-C 对高葡萄糖诱导的内皮功能障碍模型中线粒体动力学以及糖酵解和线粒体代谢的影响。高葡萄糖诱导了一种与 OPA1 蛋白表达减少、DRP1 水平升高以及基础呼吸、最大呼吸、备用呼吸能力、非线粒体耗氧量和 ATP 产生减少相关的碎片化线粒体表型。与正常葡萄糖相比。在这些条件下，PDGF-C 显著增加了 OPA1 融合蛋白的表达，降低了 DRP1 水平，并恢复了线粒体网络。在线粒体功能方面，PDGF-C 增加了高葡萄糖条件下减少的非线粒体耗氧量。这些结果表明，PDGF-C 调节了 HG 对人主动脉内皮细胞线粒体网络和形态的损伤；此外，它还补偿了 HG 诱导的能量表型改变。
