|Smith, C wayne|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract only
Publication Acceptance Date: 3/4/2004
Publication Date: 3/4/2004
Citation: Ziba, T., Forrest, L.M., Smith, C.W., Entman, M.L., Rivera, C.A. 2004. Detection of extra-nuclear high mobility group box-1 protein in a canine model of myocardial infarction [abstract]. Journal of Federation of American Societies for Experimental Biology. 18:A1006. Interpretive Summary:
Technical Abstract: The high mobility group box-1 protein (HMGB-1) is a well-characterized nuclear protein recently shown to be involved in endotoxin-induced inflammation and injury. Studies have linked HMGB-1 release to the production of pro-inflammatory cytokines; however, a role for HMGB-1 in other disorders involving a cytokine cascade has not been established. We propose that the cytokine cascade resulting from myocardial ischemia/reperfusion stimulates the release of HMGB-1, which perpetuates oxidative stress and tissue injury. To investigate this issue, 1 hr of occlusion was performed using a closed-chest method followed by reperfusion for up to 7 days. Levels of HMGB-1 were detected in samples of myocardium using immunohistochemistry. No staining was evident at the end of the ischemic period, or after 3 h of reperfusion. However, 24 h after reperfusion staining was noted in the cytoplasm of numerous myocytes throughout the reperfused tissue. Staining continued to be evident at the 7-day time point in clusters of apparently viable myocytes primarily in areas adjacent to the infarct, while myocytes in nonischemic tissue were negative. In addition, indirect immunoflorescence was used to analyze expression of the receptor for advanced glycation end products (RAGE), which has been shown to bind HMGB-1. The presence of RAGE was minimally detectable 3 hr after reperfusion and was clearly enhanced at the 3- and 7-day time points. As expected, RAGE expression appeared more pronounced near the infarct. Taken together, these results are the first indication that HMGB-1 is found in the cytoplasm of viable myocytes in a time-dependent manner following ischemia/reperfusion.