K. Pari et al., beta-Carbolines that accumulate in human tissues may serve a protective role against oxidative stress, J BIOL CHEM, 275(4), 2000, pp. 2455-2462
beta-Carbolines are tricyclic nitrogen heterocycles formed in plants and an
imals as Maillard reaction products between amino acids and reducing sugars
or aldehydes. They are being detected increasingly in human tissues, and t
heir physiological roles need to be understood. Two beta-carboline carboxyl
ates have been reported to accumulate in the human eye lens. We report here
on the identification of another beta-carboline, namely 1-methyl-1-vinyl -
2,3,4 trihydro-beta-caboline-3-carboxylic acid, in the lenses of some catar
act patients from India. Analysis of these three lenticular beta-carbolines
using photodynamic and antioxidant assays shows all of them to be inert as
sensitizers and effective as antioxidants; they quench singlet oxygen, sup
eroxide and hydroxyl radicals and inhibit the oxidative formation of higher
molecular weight aggregates of the test protein, eye lens crystallin. Such
antioxidative ability of beta-carbolines is of particular relevance to the
lens, which faces continual photic and oxidative stress. The beta-carbolin
e diacid TV is also seen to display an unexpected ability of inhibiting the
thermal coagulation of gamma-crystallin and the dithiothreitol-induced pre
cipitation of insulin. These results offer experimental support to earlier
suggestions that one of the roles that the beta-carbolines have is to offer
protection against oxidative stress to the human tissues where they accumu
late.