alpha-Lipoic acid alters post-translational modifications and protects the chaperone activity of lens alpha-crystallin in naphthalene-induced cataract.

Purpose: To evaluate whether alpha-lipoic acid (LA) inhibits lens opacity of naphthalene-induced cataract by altering post-translational modifications (PTMs) and protecting the chaperone activity of alpha-crystallins.

Methods: Forty-five Sprague-Dawley rats were divided into three groups: control, naphthalene, and naphthalene plus LA. Cataracts were induced by oral administration of 1 g naphthalene/kg body weight/day. Rats in the naphthalene plus LA group were also fed 30 mg LA/day. The development of naphthalene-initiated cataract was monitored every week by slit lamp microscopy for nine weeks, then the lens proteins were separated by HPLC, and peaks corresponding to alpha-crystallins were resolved on 2-DE. The spots of 2-DE were subjected to mass spectrometry to identify PTMs. Chaperone activity of alpha-crystallins was measured by heat-induced aggregation of betaL-crystallin.

Results: The lenses of rats fed with naphthalene plus LA exhibited less light scattering than that fed with only naphthalene at three weeks after treatment (P < 0.01). C-terminal truncated alphaA crystallin was detected in naphthalene-induced cataract and was abrogated by LA treatment. Several other post-translational modifications were identified including methylation, phosphorylation, acetylation, carbamylation, and oxidation.

Conclusions: Our data are the first to show PTM changes induced by naphthalene in rat lenses. Our findings also indicate that LA can inhibit naphthalene-induced lens opacity by altering PTM and protecting the chaperone activity of alpha-crystallins.