Levels of Coenzyme Q10 and Several COQ Proteins in Human Astrocytoma Tissues Are Inversely Correlated with Malignancy.

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 Q10 (CoQ10) levels and protein levels of polyprenyl diphosphate synthase subunit (PDSS2) and several COQ proteins required for CoQ10 biosynthesis in these tissues. We found that the level of endogenous CoQ10, 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 CoQ10 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 c 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 CoQ10 maintenance in human astrocytoma progression.

Alterations of the levels of primary antioxidant enzymes in different grades of human astrocytoma tissues.

Malignant astrocytoma is the most commonly occurring brain tumour in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumour suppressive effect in basic research, but increased SOD2 protein level was associated with higher aggressiveness of human astrocytomas. However, studies reporting alterations of antioxidant enzymes in human astrocytomas often employed less accurate methods or included different types of tumours. Here we analysed the mRNA levels, activities, and protein levels of primary antioxidant enzymes in control brain tissues and various grades of astrocytomas obtained from 40 patients. SOD1 expression, SOD1 activity, and SOD1 protein level were lower in Grade IV astrocytomas. SOD2 expression was lower in low-grade (Grades I and II) and Grade III astrocytomas than in controls, but SOD2 expression and SOD2 protein level were higher in Grade IV astrocytomas than in Grade III astrocytomas. Although there was no change in SOD2 activity and a lower activity of citrate synthase (CS), the MnSOD:CS ratio increased in Grade IV astrocytomas compared with controls and low-grade astrocytomas. Furthermore, SOD1 activity, CS activity, SOD1 expression, GPX4 expression, and GPX4 protein level were inversely correlated with the malignancy, whereas catalase activity, catalase protein, SOD2 protein level, and the SOD2:CS ratio were positively correlated with the degree of malignancy. Lower SOD2:CS ratio was associated with poor outcomes for Grade IV astrocytomas. This is the first study to quantify changes of various primary antioxidant enzymes in different grades of astrocytomas at different levels concurrently in human astrocytomas.