Glycated Proteins Stimulate Reactive Oxygen Species Production in Cardiac Myocytes

Abstract

Background— Nonenzymatic glycation that results in the production of early-glycation Amadori-modified proteins and advanced-glycation end products may be important in the pathogenesis of diabetic complications. However, the effects of early-glycated proteins, such as glycated serum albumin (Gly-BSA), are poorly defined. In this study, we investigated the effects of Gly-BSA on reactive oxygen species (ROS) production by cardiomyocytes. Methods and Results— Cultured neonatal rat cardiomyocytes were incubated with Gly-BSA or vehicle (bovine serum albumin [BSA]) for up to 48 hours. Gly-BSA dose-dependently increased in situ ROS production (whole-cell dichlorodihydrofluorescein fluorescence), with an optimum effect at 400 μg/mL after 24-hour incubation (152±10% versus BSA 100%; P Conclusions— Gly-BSA stimulates cardiomyocyte ROS production through a protein kinase C–dependent activation of a Nox2-containing NADPH oxidase, which results in nuclear factor-κB activation and upregulation of atrial natriuretic factor mRNA. These findings suggest that early-glycated Amadori products may play a role in the development of diabetic heart disease.