title: Spermidine delays eye lens opacification in vitro by suppressing transglutaminase-catalyzed crystallin cross-linking.
abstract: A Ca(2+)-dependent TG activity, identified in the eye lens of several mammalian species, has long been implicated in cataract formation. The precise mechanism of the involvement of this enzyme in this process remains unclear. The purpose of this work was to investigate the modulatory effect of polyamines on TG activity during rabbit eye lens in vitro opacification. We observed, in an in vitro Ca(2+)-induced cataract model, a rapid decrease of the endogenous levels of SPD with the progression of opacification, paralleled by an increase of crystallin cross-linking by bis(γ-glutamyl)SPD. This pattern was reversed adding exogenous SPD to the incubation medium. Indeed, endogenous SPD levels were restored and cross-linking by bis(γ-glutamyl)SPD were drastically reduced. Surprisingly, under this experimental condition, the loss of transparency of lens was delayed. We found that exogenous SPD incubation led to a remarkable increase of mono(γ-glutamyl)SPD, likely responsible of the inhibition of cross-linking of lens crystallins and of the transparency persistence.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lentini
authors.forename: Claudio
authors.initials: C
authors.lastname: Tabolacci
authors.forename: Palma
authors.initials: P
authors.lastname: Mattioli
authors.forename: Bruno
authors.initials: B
authors.lastname: Provenzano
authors.forename: Simone
authors.initials: S
authors.lastname: Beninati
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D058442:Capsule Opacification / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D002386:Cataract / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D003459:Crystallins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D007908:Lens, Crystalline / Q000201:enzymology*; D011817:Rabbits; D013095:Spermidine / Q000494:pharmacology*; D013096:Spermine / Q000737:chemistry; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D003459:Crystallins; D013096:Spermine; D011503:Transglutaminases; D002118:Calcium; D013095:Spermidine