Direct Oxidation of Calcium/Calmodulin Dependent Protein Kinase II and Associated Diagnostic and Therapeutic Methods

摘要

Calcium/calmodulin dependent protein kinase II (CaMKII) has been found to be directly oxidized, and direct oxidation of CaMKII was observed to result in calcium independent activation of CaMKII. Antibodies that bind specifically to oxidized forms of CaMKII (oxCaMKII) were generated and were utilized to detect oxCaMKII in blood from: (1) mice with cancer; (2) mice with a knock out of the gene encoding methionine sulfoxide reductase; (3) mice injected with angiotensin II; (4) mice injected with bacterial endotoxin; (5) mice fed a pro-oxidant (ketogenic) diet; and (6) mice with cancer that had been treated with experimental therapy.