The fluorescence of scorpions and cataractogenesis

Background: Protein cross-linking and fluorescence are widely recognized ma rkers of oxidative aging in human proteins. Oxidative protein aging is a co mbinatorial process in which diversity arises from the heterogeneity of the targets and is amplified by the nonselective nature of the reactants. The crosslinks themselves defy analysis because they are generally embedded in a covalent matrix. Arthropods rely upon oxidative cross-linking in the hard ening of the cuticle - a process known as sclerotization, Among arthropods, scorpions are noteworthy in that the process of sclerotization is accompan ied by the buildup of strong visible fluorescence. To date, the nature of t he fluorescent species has remained a mystery. Results: We have identified one of the soluble fluorescent components of th e scorpions Centuroides vittatus and Pandinus imperator as beta-carboline - a tryptophan derivative that has previously been identified by hydrolysis a nd oxidation of lens protein. We have also shown that beta-carboline-3-carb oxylic acid is released from both scorpion exuvia (the shed cuticle) and hu man cataracts upon hydrolysis, suggesting that the protein-bound beta-carbo line and free beta-carboline have common chemical origins. Conclusions: Cataractogenesis and cuticular sclerotization are disparate ox idative processes - the former is collateral and the latter is constitutive . The common formation of beta-carbolines shows that similar patterns of re activity are operative. These fundamental mechanisms provide predictive ins ight into the consequences of human protein aging.