血清反应因子
线粒体
氧化磷酸化
化学
尼泊尔卢比1
肌动蛋白
细胞生物学
磷酸化
转录因子
组蛋白
乙酰化
生物化学
分子生物学
生物
线粒体生物发生
基因
作者
Pankaj Patyal,Bachkhoa Nguyen,Xiaomin Zhang,Gohar Azhar,Fathima S. Ameer,Ashwani Kumar Verma,Jasmine Crane,Grishma Kc,Yingni Che,Jeanne Y. Wei
标识
DOI:10.3390/ijms231911536
摘要
CCG-1423 is a Rho A pathway inhibitor that has been reported to inhibit Rho/SRF-mediated transcriptional regulation. Serum response factor and its cofactors, which include ternary complex factors and myocardin-related transcription factors, regulate various cellular functions. In this study, we observed that CCG-1423 modulates the mitochondrial functions. The effect of this small molecule drug was determined by measuring mitochondrial function using an XFe96 Analyzer and an Oxygraph 2k (O2k) high-resolution respirometer. CCG-1423 treatment significantly reduced oxidative phosphorylation in a dose-dependent manner. However, CCG-1423 increased the glycolytic rate. We also observed that histone 4 at lysine-16 underwent hyperacetylation with the treatment of this drug. Immunolabeling with F-actin and MitoTracker revealed the alteration in the actin cytoskeleton and mitochondria. Taken together, our findings highlight a critical role of CCG-1423 in inhibiting the transcription of SRF/p49 and PGC-1α, β, resulting in the downregulation of mitochondrial genes, leading to the repression of mitochondrial oxidative phosphorylation and overall ATP reduction. This study provides a better understanding of the effects of CCG-1423 on mitochondria, which may be useful for the assessment of the potential clinical application of CCG-1423 and its derivatives.
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