tailieunhanh - Proteomics Human Diseases and Protein Functions Part 11

Tham khảo tài liệu 'proteomics human diseases and protein functions part 11', khoa học tự nhiên, công nghệ sinh học phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | 11 Posttranslational Modifications of Myosin Light Chains Determine the Protein Fate Virgilio J. J. Cadete and Grzegorz Sawicki University of Saskatchewan College of Medicine Department of Pharmacology Canada 1. Introduction The advances in proteomics over the last decade have made it possible for a more detailed study of protein posttranslational modifications. Posttranslational modification of proteins is an important signaling mechanism regulating vital pathways ranging from transcription to translation in metabolism cell survival and cell death. Posttranslational modification of proteins has commonly been associated with the loss gain of function and signal transduction with the concept of phosphorylation being the hallmark. However many other posttranslational modifications of proteins have been detected and their implication to overall cellular homeostasis remains to be elucidated. The cardiovascular system in particular the heart due to its high metabolic rates sensitivity to oxidative stress and necessity to adapt quickly to new environments is an ideal candidate to the study of posttranslational modifications in physiology and pathology. Cardiac contractile function relies significantly on the integrity of its contractile apparatus with the myosin light chains being important contractile elements. We have recently described the role of nitration and nitrosylation of ventricular myosin light chains MLCs on its degradation by the proteolytic enzyme matrix metalloproteinase-2 MMP-2 Doroszko et al. 2010 Doroszko et al. 2009 Polewicz et al. 2010 . Using distinct experimental models of oxidative stress such as hypoxia-reoxygenation or ischemia reperfusion we have detected pathological nitration and nitrosylation of MLC induced by oxidative stress. According to our findings nitration and nitrosylation of MLCs is associated with an increased affinity for MMP-2 and a consequent increase in degradation of these proteins that is associated with a worsening in cardiac