α-Lipoic Acid Alters Post-Translational Modifications and Protects the Chaperone Activity of Lens α-Crystallin in Naphthalene-Induced Cataract

Abstract

Purpose: To evaluate whether α-lipoic acid (LA) inhibits lens opacity of naphthalene-induced cataract by altering post-translational modifications (PTMs) and protecting the chaperone activity of α-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 α-crystallins were resolved on 2-DE. The spots of 2-DE were subjected to mass spectrometry to identify PTMs. Chaperone activity of α-crystallins was measured by heat-induced aggregation of βL-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 αA 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 α-crystallins.

KEYWORDS::

• α-Lipoic acid
• Cataract
• α-Crystallins
• Molecular chaperone
• Post-translational modifications

ACKNOWLEDGMENTS

The authors thank Dr. Laney Weber (Ph D) for providing helpful writing revision. This work was supported by ShangHai Committee for Science and Technology (08411963300 to L.Y).

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.