β-Carbolines that accumulate in human tissues may serve a protective role against oxidative stress

Abstract

β-Carbolines are tricyclic nitrogen heterocycles formed in plants and animals as Maillard reaction products between amino acids and reducing sugars or aldehydes. They are being detected increasingly in human tissues, and their physiological roles need to be understood. Two β-carboline carboxylates have been reported to accumulate in the human eye lens. We report here on the identification of another β-carboline, namely 1-methyl-1-vinyl -2,3,4-trihydro-β-carboline-3-carboxylic acid, in the lenses of some cataract patients from India. Analysis of these three lenticular β-carbolines using photodynamic and antioxidant assays shows all of them to be inert as sensitizers and effective as antioxidants; they quench singlet oxygen, superoxide and hydroxyl radicals and inhibit the oxidative formation of higher molecular weight aggregates of the test protein, eye lens γ-crystallin. Such antioxidative ability of β-carbolines is of particular relevance to the lens, which faces continual photic and oxidative stress. The β-carboline diacid IV is also seen to display an unexpected ability of inhibiting the thermal coagulation of γ-crystallin and the dithiothreitol-induced precipitation of insulin. These results offer experimental support to earlier suggestions that one of the roles that the β-carbolines have is to offer protection against oxidative stress to the human tissues where they accumulate.