Abstract
We characterized γ-cystathionase, rhodanese and 3-mercaptopyruvate sulfurtransferase activities in various regions of human brain (the cortex, thalamus, hypothalamus, hippocampus, cerebellum and subcortical nuclei) and human gliomas with II to IV grade of malignancy (according to the WHO classification). The human brain regions, as compared to human liver, showed low γ-cystathionase activity. The activity of rhodanese was also much lower and it did not vary significantly between the investigated brain regions. The activity of 3-mercaptopyruvate sulfurtransferase was the highest in the thalamus, hypothalamus and subcortical nuclei and essentially the same level of sulfane sulfur was found in all the investigated brain regions. The investigations demonstrated that the level of sulfane sulfur in gliomas with the highest grades was high in comparison to various human brain regions, and was correlated with a decreased activity of γ-cystathionase, 3-mercaptopyruvate sulfurtransferase and rhodanese. This can suggest sulfane sulfur accumulation and points to its importance for malignant cell proliferation and tumor growth. In gliomas with the highest grades of malignancy, despite decreased levels of total free cysteine and total free glutathione, a high ratio of GSH/GSSG was maintained, which is important for the process of malignant cells proliferation. A high level of sulfane sulfur and high GSH/GSSG ratio could result in the elevated hydrogen sulfide levels. Because of the disappearance of γ-cystathionase activity in high-grade gliomas, it seems to be possible that 3-mercaptopyruvate sulfurtransferase could participate in hydrogen sulfide production. The results confirm sulfur dependence of malignant brain tumors.
Highlights
L-Cysteine desulfuration, a source of sulfane sulfur-containing compounds, has not been extensively investigated in the human brain
The objective of the present study was to investigate L-cysteine desulfuration (Scheme 1) in various regions of human brain and in human gliomas of various grades of malignancy, through the estimation of the activity of enzymes participating in the formation and metabolism of sulfane sulfur compounds, i.e., cystathionine γ-lyase (CTH, EC 4.4.1.1), 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2), rhodanese, and through the determination of the level of sulfane sulfur, cysteine, glutathione and cystathionine
The highest value of the activity of MPST was found in the thalamus and it was significantly higher than the value determined in the hypothalamus (Table 1)
Summary
L-Cysteine desulfuration, a source of sulfane sulfur-containing compounds, has not been extensively investigated in the human brain. Sulfane sulfur is involved in the detoxification of cyanide and inorganic sulfide, the incorporation of sulfur in iron-sulfur centers of redox proteins, enzyme activity regulation through a mechanism that involves the incorporation of sulfur, sulfuration of tRNA; it has an antioxidant potential and may affect the toxic function of exogenous xenobiotics or drugs (not reviewed here, but see [1,2]). The objective of the present study was to investigate L-cysteine desulfuration (Scheme 1) in various regions of human brain and in human gliomas of various grades of malignancy, through the estimation of the activity of enzymes participating in the formation and metabolism of sulfane sulfur compounds, i.e., cystathionine γ-lyase (CTH, EC 4.4.1.1), 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2), rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1), and through the determination of the level of sulfane sulfur, cysteine, glutathione and cystathionine.
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