Aminothiols in human brain tumors

Abstract

Aminothiols are sulfur-containing amino acids involved in methionine metabolism. Changes in their levels play negative roles in the genesis of many diseases. These mechanisms involve direct toxicity, either on glutamate neurotransmitter receptors or cerebrovascular endothelium, and have an indirect inhibitory effect on transmethylation reactions. Oxidative stress and excitotoxicity are factors that may rise as a consequence of increased homocysteine levels in brain tissues. We discovered new information concerning concentrations of the main aminothiols in human neoplastic brain tissues. The cytosolic fractions of 73 tissue samples from human brain tumors were used for the determination of total homocysteine, total cysteine and methionine levels. Gas chromatography with flame ionization detection after reduction of disulfide bonds was the method used. Average concentrations of the aminothiols examined were as follows: total homocysteine, 0.58-1.51 nmol/mg; methionine, 1.16-2.07 nmol/mg; and total cysteine 5.08-7.82 nmol/mg of total protein. Significantly higher levels of total homocysteine were found in pituitary adenoma and glioblastoma multiforme compared with other types of tumors. Methionine and cysteine concentrations did not differ significantly according to diagnosis. This is the first work concerning the concentrations of aminothiols in brain tissues. The results obtained indicate the metabolic pathways that are involved in tumor formation and/or its progress, including the toxic effects of homocysteine.