title: Is development of high-grade gliomas sulfur-dependent?
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.
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7 St., Kraków 31-034, Poland. mbwrobel@cyf-kr.edu.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Wróbel
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7 St., Kraków 31-034, Poland. jerzy.czubak@uj.edu.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Czubak
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7 St., Kraków 31-034, Poland. mbbronow@cyf-kr.edu.pl.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Bronowicka-Adamska
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7 St., Kraków 31-034, Poland. mbjurkow@cyf-kr.edu.pl.
authors.forename: Halina
authors.initials: H
authors.lastname: Jurkowska
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, Grzegórzecka 16 St., Kraków 31-531, Poland. dariusz.adamek@uj.edu.pl.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Adamek
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, Grzegórzecka 16 St., Kraków 31-531, Poland. bolekpapla@gmail.com.
authors.forename: Bolesław
authors.initials: B
authors.lastname: Papla
mesh_terms: D000328:Adult; D001921:Brain / Q000201:enzymology*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D003540:Cystathionine / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D013466:Sulfurtransferases / Q000378:metabolism; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D055815:Young Adult
chemical_list: D003540:Cystathionine; D013466:Sulfurtransferases; D013884:Thiosulfate Sulfurtransferase; C021550:3-mercaptopyruvate sulphurtransferase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D006862:Hydrogen Sulfide