Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, USA.
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, USA; Department of Biological Sciences, Northern Illinois University, DeKalb, IL, USA.
Nitric Oxide. 2018 Sep 1;79:51-56. doi: 10.1016/j.niox.2018.07.006. Epub 2018 Jul 25.
Age-related macular degeneration (AMD) is a disease characterized by degenerative changes in the retinal pigment epithelium and Bruch's membrane. Inflammation is considered a major risk factor for the development and progression of AMD. Nitrite is a potent byproduct of inflammation and has been detected at elevated concentrations in AMD donor tissue. We hypothesize that nitrite chemically modifies the extracellular matrix (ECM) of Bruch's membrane as an initial step to degenerative changes observed in AMD. Non-enzymatically nitrated synthetic ECM peptides, fibronectin and laminin, were used as model systems for inflammation. Using LC/MS, we identified that nitration preferentially occurred on tyrosine and deamination of lysine under the studied conditions. At tyrosine residues, 3-nitrotyrosine was produced and shifted the total mass by the addition of 45 amu. Deamination of lysine occurred and resulted in the formation of either an alkene or alcohol group. The alkene group was observed with a loss of 17 amu. An addition of 1 amu was observed with alcohol formation. We hypothesize that these initial chemical modifications to the structure of ECM proteins may be the responsible for altering the structure and consequent function of Bruch's membrane.
年龄相关性黄斑变性（AMD）是一种以视网膜色素上皮和布鲁赫膜退行性改变为特征的疾病。炎症被认为是 AMD 发生和发展的主要危险因素。亚硝酸盐是炎症的一种强效副产物，在 AMD 供体组织中检测到浓度升高。我们假设亚硝酸盐作为退行性改变的初始步骤，化学修饰了布鲁赫膜的细胞外基质（ECM）。使用非酶促硝化合成 ECM 肽，纤连蛋白和层粘连蛋白作为炎症的模型系统。通过 LC/MS，我们确定硝化优先发生在酪氨酸上，赖氨酸在研究条件下发生脱氨。在酪氨酸残基上，生成 3-硝基酪氨酸，通过添加 45 amu 来改变总质量。赖氨酸脱氨发生，导致形成烯烃或醇基。观察到烯烃基团丢失 17 amu。醇形成时观察到添加 1 amu。我们假设 ECM 蛋白结构的这些初始化学修饰可能是导致布鲁赫膜结构和功能改变的原因。
