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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Antipyrine, Apoptosis, Cells, Cultured, Chemokines, Cytokines, DNA-Binding Proteins, Disease Models, Animal, Edaravone, Endoplasmic Reticulum, Free Radical Scavengers, Gene Expression Regulation, Inflammation, Inflammation Mediators, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardial Reperfusion Injury, Myocardium, RNA Splicing, RNA, Messenger, Regulatory Factor X Transcription Factors, Stress, Physiological, Superoxides, Thapsigargin, Time Factors, Transcription Factor CHOP, Transcription Factors.
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Does c/EBP homologous protein deficiency attenuate myocardial reperfusion injury by inhibiting myocardial apoptosis and inflammation? Context: To investigate whether and how the endoplasmic reticulum (ER) stress-induced, CCAAT/enhancer-binding protein-homologous protein (CHOP)-mediated pathway regulates myocardial ischemia/reperfusion injury. Wild-type and chop-deficient mice underwent 50 minutes of left coronary artery occlusion followed by reperfusion. Expression of chop and spliced x-box binding protein-1 (sxbp1) mRNA was rapidly and significantly increased in reperfused myocardium of wild-type mice. chop-deficient mice exhibited markedly reduced injury size after reperfusion compared with wild-type mice, accompanied by a decreasing number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cardiomyocytes. Interestingly, myocardial inflammation, as assessed by expression of inflammatory cytokines and chemokines and numbers of infiltrated inflammatory cells, was also attenuated in chop-deficient mice. Moreover, expression of interleukin-6 mRNA in response to lipopolysaccharide was enhanced by simultaneous stimulation with thapsigargin, a potent ER stressor, in wild-type cardiomyocytes but not in chop-deficient cardiomyocytes. Finally, we found that superoxide was produced in reperfused myocardium and that intravenous administration of edaravone, a free radical scavenger, immediately before reperfusion significantly suppressed the superoxide overproduction and subsequent expression of sxbp1 and chop mRNA, followed by reduced injury size in wild-type mice.
assistant
The ER stress-induced, CHOP-mediated pathway, which is activated in part by superoxide overproduction after reperfusion, exacerbates myocardial ischemia/reperfusion injury by inducing cardiomyocyte apoptosis and myocardial inflammation. Final Decision: yes