Morphological and functional changes in the mammalian retina to photoreceptor cell death have been observed following light exposure. Little is known about the molecular mechanism of light damage nor about protein modifications caused by light exposure. Nitric oxide (NO), which is biological precursor molecule for nitrating agents in vivo has been suggested to mediate light-induced photoreceptor degeneration. In addition, preliminary proteomic studies suggest that light exposure induces protein nitration and changes protein expression levels. The hypothesis of this proposal is that light exposure causes protein nitration that alter the function of the protein and mediate photoreceptor cell death. Proteomic studies are expressed to evaluate the in vivo effect of intense light exposure on rat retinal protein nitration and expression.
The specific aims are: 1) Determine light-induced nitric oxide synthase (NOS) expression, NO production and nitrotyrosine formation in rat retina, 2) Identify changes in protein expression levels and proteins which are nitrated by night exposure in whole rat retina and rod outer segments, and 3) Characterize structural changes in LEDGF induced by light exposure. Results will reveal protein targets of nitration and proteins up and down regulated by light exposure. The results will lead to a better understanding of the mechanisms associated with retinal light damage.
| Miyagi, Masaru; Rao, K C Sekhar (2007) Proteolytic 18O-labeling strategies for quantitative proteomics. Mass Spectrom Rev 26:121-36 |
| Hajkova, Dagmar; Rao, K C Sekhar; Miyagi, Masaru (2006) pH dependency of the carboxyl oxygen exchange reaction catalyzed by lysyl endopeptidase and trypsin. J Proteome Res 5:1667-73 |
| Palamalai, Vikram; Darrow, Ruth M; Organisciak, Daniel T et al. (2006) Light-induced changes in protein nitration in photoreceptor rod outer segments. Mol Vis 12:1543-51 |
| Rao, K C Sekhar; Palamalai, Vikram; Dunlevy, Jane R et al. (2005) Peptidyl-Lys metalloendopeptidase-catalyzed 18O labeling for comparative proteomics: application to cytokine/lipolysaccharide-treated human retinal pigment epithelium cell line. Mol Cell Proteomics 4:1550-7 |
| Sakaguchi, Hirokazu; Miyagi, Masaru; Darrow, Ruth M et al. (2003) Intense light exposure changes the crystallin content in retina. Exp Eye Res 76:131-3 |
