Methylglyoxal inhibits glycation-mediated loss in chaperone function and synthesis of pentosidine in alpha-crystallin.
Alpha-crystallin is a major protein in the eye lens and it functions as a molecular chaperone by preventing aggregation of mildly denatured proteins. Glycation, the reaction of sugars and ascorbate with proteins, causes covalent cross-linking and reduces the chaperone function of alpha-crystallin. We demonstrated that methylglyoxal (MGO), a metabolic alpha-dicarbonyl compound, modifies arginine residues in alpha-crystallin and enhances its chaperone function. We wanted to determine whether modification by MGO could protect alpha-crystallin from glycation-mediated cross-linking and loss of chaperone function. Our results show that MGO-modification of isolated bovine lens alpha-crystallin inhibits formation of pentosidine, a glycation-derived protein crosslink. Proteins in organ cultured rat lenses were similarly protected from pentosidine formation. Glycation by sugars and ascorbate resulted in almost complete loss of chaperone function of alpha-crystallin. Surprisingly, addition of MGO during or before glycation not only inhibited the loss of chaperone function, but it actually enhanced the chaperone function of alpha-crystallin. Together, these data suggest that in the aging lens, MGO inhibits glycation-mediated pentosidine synthesis and the loss of chaperone function of alpha-crystallin.
Puttaiah
Shivaprakash
S
Department of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA.
Biswas
Ashis
A
Staniszewska
Magdalena
M
Nagaraj
Ram H
RH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism; D006031:Glycosylation; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D018832:Molecular Chaperones / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D038201:alpha-Crystallins / Q000378:metabolism*
D005136:Eye Proteins; D018832:Molecular Chaperones; D038201:alpha-Crystallins; D011765:Pyruvaldehyde; D001120:Arginine; C062187:pentosidine; D008239:Lysine