Proteomic method identifies proteins nitrated in vivo during inflammatory challenge

Inflammation in asthma, sepsis, transplant rejection, and many neurodegener ative diseases associates an up-regulation of NO synthesis with increased p rotein nitration at tyrosine. Nitration can cause protein dysfunction and i s implicated in pathogenesis, but few proteins that appear nitrated in vivo have been identified. To understand how this modification impacts physiolo gy and disease, we used a proteomic approach toward targets of protein nitr ation in both in vivo and cell culture inflammatory disease models. This ap proach identified more than 40 nitrotyrosine-immunopositive proteins, inclu ding 30 not previously identified, that became modified asa consequence of the inflammatory response. These targets include proteins involved in oxida tive stress, apoptosis, ATP production, and other metabolic functions. Our approach provides a means toward obtaining a comprehensive view of the nitr oproteome and promises to broaden understanding of how NO regulates cellula r processes.