Involvement of asparatic acid isomerization in the pathogenesis ofCOPD

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The pathogenesis of COPD involves posttranslational modification, including amino acid racemization and isomerization and damage in the protein induced by oxidative stress through mainly cigarette smoking. The modified and damaged proteins are susceptible to cell damage such as apoptosis or ER stress. Notably, asparatic acid and asparagine are more sensitive amino acids to oxidative stress. In the COPD cases, we investiga ted signs of oxidative stress from the point of asparatic acid isomerization in the proteins.Methods:Lung specimens surgically isolated from COPD patients or other controls without COPD were utilized to detect D -asparatic acid. To investigate exhaustively D-asparatic acid isomerization in the protein, we employed a paenidase I, D -asparatic asic specific endopeptidase, in combination with comparative two dimensional electrophoresis analysis.The endopeptidase sensitive proteins revealed decreased amounts of intensity in the proteins. The sensitive proteins were identified by mass spectrometry analysis. Furthermore, we studied the asparatic acid isomerization in vitro using cell culture system under cigarette smoke exposure. Results and discussion : In the proteins from COPD lung, 4 isomerized proteins, Prohibitin, Peroxiredoxin-2, Gkutathione S-transferase Pi, and serum amyloid p component, were detected significantly as evaluated by 30~40% compared to ~7% in control patients. Further, in vitro studies, cigarette smoke extracts induced ER stress marker and increased the ratio of the isomerized proteins. We conclude that protein isomerization process is involved in the pathogenesis of COPD.