Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan.
Biomolecules. 2022 Feb 20;12(2):336. doi: 10.3390/biom12020336.
In a previous study, we reported the alterations of primary antioxidant enzymes and decreased citrate synthase (CS) activities in different grades of human astrocytoma tissues. Here, we further investigated coenzyme Q (CoQ) levels and protein levels of polyprenyl diphosphate synthase subunit (PDSS2) and several COQ proteins required for CoQ biosynthesis in these tissues. We found that the level of endogenous CoQ, but not of exogenous α-tocopherol, was higher in nontumor controls than in all grades of astrocytoma tissues. The levels of COQ3, COQ5, COQ6, COQ7, COQ8A, and COQ9, but not of COQ4, were lower in Grade IV astrocytoma tissues than in controls or low-grade (Grades I and II) astrocytomas, but PDSS2 levels were higher in astrocytoma tissues than in controls. Correlation analysis revealed that the levels of CoQ and COQ proteins were negatively correlated with malignancy degree and positively correlated with CS activity, whereas PDSS2 level was positively correlated with malignancy. Moreover, lower level of mitochondrial DNA-encoded cytochrome oxidase subunit 2 was not only associated with a higher malignancy degree but also with lower level of all COQ proteins detected. The results revealed that mitochondrial abnormalities are associated with impaired CoQ maintenance in human astrocytoma progression.
在之前的研究中，我们报道了人星形细胞瘤组织中初级抗氧化酶的改变和柠檬酸合酶（CS）活性的降低。在这里，我们进一步研究了辅酶 Q（CoQ）水平和多聚异戊二烯二磷酸合酶亚基（PDSS2）以及几种 CoQ 生物合成所需的 COQ 蛋白的蛋白水平在这些组织中。我们发现，内源性 CoQ 的水平，而不是外源性α-生育酚的水平，在非肿瘤对照中高于所有星形细胞瘤组织的等级。COQ3、COQ5、COQ6、COQ7、COQ8A 和 COQ9 的水平，但不是 COQ4 的水平，在 IV 级星形细胞瘤组织中低于对照或低级别（I 和 II 级）星形细胞瘤，但 PDSS2 水平在星形细胞瘤组织中高于对照。相关性分析显示，CoQ 和 COQ 蛋白的水平与恶性程度呈负相关，与 CS 活性呈正相关，而 PDSS2 水平与恶性程度呈正相关。此外，线粒体 DNA 编码的细胞色素氧化酶亚基 2 的水平较低不仅与更高的恶性程度相关，而且与所有检测到的 COQ 蛋白水平较低相关。结果表明，线粒体异常与人类星形细胞瘤进展中 CoQ 维持受损有关。
