The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Carboxyethylpyrrole Protein Adducts and Autoantibodies, Biomarkers for Age-related Macular Degeneration
Open accessAbstract
Age-related macular degeneration (AMD) is a slow, progressive disease with both genetic and environmental risk factors. Free radical-induced oxidation of docosahexaenoate (DHA)-containing lipids generates omega-(2-carboxyethyl)pyrrole (CEP) protein adducts that are more abundant in ocular tissues from AMD than normal human donors. To understand better the role of oxidative damage in AMD, we have synthesized CEP-modified proteins, produced anti-CEP antibodies, and initiated analysis of CEP immunoreactivity and autoantibodies in human plasma. A highly selective rabbit polyclonal anti-CEP antibody was raised that binds CEP 1000 times more strongly than carboxypropylpyrrole, a close structural analogue. The CEP adduct uniquely indicates oxidative modification from DHA derivatives because CEP protein modifications cannot arise from any other common polyunsaturated fatty acid. Immunocytochemistry localized CEP to photoreceptor rod outer segments and retinal pigment epithelium in mouse retina and demonstrated more intense CEP immunoreactivity in photoreceptors from a human AMD donor compared with healthy human retina. The mean level of anti-CEP immunoreactivity in AMD human plasma (n = 19 donors) was 1.5-fold higher (p = 0.004) than in age-matched controls (n = 19 donors). Sera from AMD patients demonstrated mean titers of anti-CEP autoantibody 2.3-fold higher than controls (p = 0.02). Of individuals (n = 13) exhibiting both antigen and autoantibody levels above the mean for non-AMD controls, 92% had AMD. These results suggest that together CEP immunoreactivity and autoantibody titer may have diagnostic utility in predicting AMD susceptibility.
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Cites
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Self-citationChemistry and metabolism of lipids in the vertebrate retina
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The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 802
Oxidative damage-induced inflammation initiates age-related macular degeneration
Hollyfield, J. G., Bonilha, V. L., Rayborn, M. E., Yang, X., Shadrach, K. G., Lu, L., Ufret, R. L., Salomon, R. G., & Perez, V. L. (2008) · Nature Medicine · doi:10.1038/nm1709 · Cited by 710
Self-citationPara-Inflammation in the Aging Retina
Xu, H., Chen, M., & Forrester, J. V. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.06.001 · Cited by 659
Inflammation and its role in age-related macular degeneration
Kauppinen, A., Paterno, J. J., Blasiak, J., Salminen, A., & Kaarniranta, K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2147-8 · Cited by 649
Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait
Wright, A. F., Chakarova, C. F., Abd El-Aziz, M. M., & Bhattacharya, S. S. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2717 · Cited by 631
Metadata
- Authors
- Gu, X., Meer, S. G., Miyagi, M., Rayborn, M. E., Hollyfield, J. G., Crabb, J. W., & Salomon, R. G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 278
- Issue
- 43
- Pages
- 42027-42035
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1985235161
- Cited by
- 325
- References
- 10
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Gu, X., Meer, S. G., Miyagi, M., Rayborn, M. E., Hollyfield, J. G., Crabb, J. W., & Salomon, R. G. (2003). Carboxyethylpyrrole Protein Adducts and Autoantibodies, Biomarkers for Age-related Macular Degeneration. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m305460200
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