a Department of Medical Biotechnology and Laboratory Science, College of Medicine , Chang Gung University , Taoyuan , Taiwan.
b Department of Nephrology , Linkou Chang Gung Memorial Hospital , Taoyuan , Taiwan.
Free Radic Res. 2018 Aug;52(8):856-871. doi: 10.1080/10715762.2018.1483580.
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.
恶性星形细胞瘤是人类最常见的脑肿瘤。氧化应激与癌症的发展有关。在基础研究中发现超氧化物歧化酶 2（SOD2）具有肿瘤抑制作用，但 SOD2 蛋白水平的增加与人类星形细胞瘤的侵袭性更高有关。然而，报道抗氧化酶在人类星形细胞瘤中变化的研究通常采用不太准确的方法或包括不同类型的肿瘤。在这里，我们分析了 40 名患者的对照脑组织和各种分级星形细胞瘤中主要抗氧化酶的 mRNA 水平、活性和蛋白水平。SOD1 表达、SOD1 活性和 SOD1 蛋白水平在 IV 级星形细胞瘤中较低。SOD2 表达在低级别（I 和 II 级）和 III 级星形细胞瘤中低于对照组，但在 IV 级星形细胞瘤中高于 III 级星形细胞瘤。尽管 SOD2 活性没有变化，柠檬酸合酶（CS）活性较低，但 MnSOD:CS 比值在 IV 级星形细胞瘤中与对照组和低级别星形细胞瘤相比增加。此外，SOD1 活性、CS 活性、SOD1 表达、GPX4 表达和 GPX4 蛋白水平与恶性程度呈负相关，而过氧化氢酶活性、过氧化氢酶蛋白、SOD2 蛋白水平和 SOD2:CS 比值与恶性程度呈正相关。较低的 SOD2:CS 比值与 IV 级星形细胞瘤的不良预后相关。这是首次在人类星形细胞瘤中同时在不同级别和不同水平上定量研究各种主要抗氧化酶在不同级别星形细胞瘤中的变化。
