Abstract T P218: Peripheral Organ Proteomics, a Novel Approach to Biomarker Discovery for Brain Disorders
Introduction: Brain disorders may produce changes in function of peripheral organs. The lack of omics characterization of peripheral organs hinders development of novel approaches for diagnosing/managing brain disorders. We have characterized proteomes of ischemic brain injury (Stapels et al., 2010, Science Signaling 3 (111):ra15).
Here, we demonstrate: 1) Acute brain disorders induce systemic responses in peripheral proteomes; 2) Brain disorder-induced peripheral proteomic changes are specific to injury conditions. Renal proteomic responses to focal brain ischemia are examples.
Methods Ischemia: suture occlusion (30 or 60 minutes: n=5, sham: n=4) of middle cerebral artery (MCAO) in mice. After 4 hours reperfusion, brain cortices and one kidney were removed at sacrifice. Proteins were extracted from individual tissues. Tryptic digests from animals of the same experimental group were pooled, and analyzed by quantitative mass spectrometry with triplicate replications. Proteins showing differences in abundance between sham and 30 minutes or 60 minutes brain ischemia were further analyzed by bioinformatics.
Results and Conclusion: At 4 hours after 30 or 60 minutes MCAO, kidney proteome showed significant changes compared to that of sham controls: 72 and 56 proteins with increased abundance in the former and latter brain conditions, respectively. Interestingly, among up-regulated proteins, only 24 showed an overlap between the 30 and 60 minute brain ischemic conditions. Results of bioinformatic analyses of regulated kidney proteins indicated an association with cellular pathways or processes of cell adhesion, small molecule metabolism, protein folding, as well as immune response, for both brain ischemic conditions. Differential changes were also observed: an increase of amino acid metabolism and nucleoside catabolic processes were detected only in 60 but not 30 minutes brain ischemic conditions. Our previous work has shown that 30 minutes MCAO results in very limited cortical injury whereas 60 minutes MCAO leads to broad tissue infarction. Hence, our results present distinguishable kidney proteomic characteristics associated with different brain ischemic conditions.
Author Disclosures: L. Cao: None. F. Bian: None. E. Umejiego: None. T. Yang: None. S.P. Simon: None. A. Zhou: None.
- © 2014 by American Heart Association, Inc.