Inhibition of Methylglyoxal-Mediated Protein Modification in Glyoxalase I Overexpressing Mouse Lenses.pdfVIP

Hindawi Publishing Corporation Journal of Ophthalmology Volume 2010, Article ID 274317, 7 pages doi:10.1155/2010/274317 Research Article Inhibition of Methylglyoxal-Mediated Protein Modification in Glyoxalase I Overexpressing Mouse Lenses Mahesha H. Gangadhariah,1 Maneesh Mailankot,1 Lixing Reneker,2 and Ram H. Nagaraj1 1 Department of Ophthalmology Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA 2 Mason Eye Institute, University of Missouri, Columbia, MO 65212, USA Correspondence should be addressed to Ram H. Nagaraj, nhr@ Received 1 March 2010; Accepted 1 June 2010 Academic Editor: Mark Petrash Copyright © 2010 Mahesha H. Gangadhariah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Here we tested the role of Glo I in the prevention of advanced glycation end product (AGE) formation in transgenic mouse lenses. Methods. A transgenic animal line that expressed high levels of human Glo I in the lens was developed from the C57B6 mouse strain. The role of Glo I in the inhibition of MGO-AGE formation was tested in organ-cultured lenses. Results. Organ culture of Wt and Glo I lenses with 5 mM D, L-glyceraldehyde (GLD) enhanced MGO by 29-fold and 17-fold in Wt lenses and Glo I lenses, respectively. Argpyrimidine levels were 192 ± 73 pmoles/mg protein, and hydroimidazolone levels were 22 ± 0.7 units/μg protein in GLD-incubated Wt lenses. In Glo I lenses, formation of AGEs was significantly inhibited; the argpyrimidine levels were 82 ± 18 pmoles/mg protein, and the HI levels were 2.6 ± 2.3 units/μg protein. Incubation of Wt lens proteins with 5 mM rib