alpha-Lipoic acid alters post-translational modifications and protects the chaperone activity of lens alpha-crystallin in naphthalene-induced cataract.
OBJECTIVE
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.
Chen
Yan
Y
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
Yi
Lu
L
Yan
GuoQuan
G
Fang
YanWen
Y
Jang
YongXiang
Y
Wu
XinHua
X
Zhou
XinWen
X
Wei
LiMing
L
D000107:Acetylation; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D018832:Molecular Chaperones / Q000378:metabolism*; D009281:Naphthalenes; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D008063:Thioctic Acid / Q000494:pharmacology*; D038201:alpha-Crystallins / Q000378:metabolism*
D000975:Antioxidants; D018832:Molecular Chaperones; D009281:Naphthalenes; D038201:alpha-Crystallins; C031721:naphthalene; D008063:Thioctic Acid