Aims: Excess catecholamine levels are suggested to be cardiotoxic and to underlie stress-induced heart failure. The cardiotoxic effects of noradrenaline and adrenaline are well recognized. However, although cardiac and circulating dopamine levels are also increased in stress-cardiomyopathy patients, knowledge regarding putative toxic effects of excess dopamine levels on cardiomyocytes is scarce. We now studied the effects of elevated dopamine levels in H9C2 cardiomyoblasts. Methods and Results: H9C2 cells were cultured and treated with dopamine (200 μM) for 6, 24 and 48 hours. Subsequently, the effects on lipid accumulation, cell viability, flippase activity, reactive oxygen species (ROS) production, subcellular NOX protein expression and ATP/ADP and GTP/GDP levels were analysed. Dopamine did not result in cytotoxic effects after 6 hours. However, after 24 and 48 hours dopamine treatment induced a significant increase in lipid accumulation, nitrotyrosine levels, indicative of ROS production, and cell death. In addition, dopamine significantly reduced flippase activity and ATP/GTP levels, coinciding with phosphatidylserine exposure on the outer plasma membrane. Furthermore, dopamine induced a transient increase in cytoplasmic and (peri)nucleus NOX1 and NOX4 expression after 24 hours, which subsided after 48 hours. Moreover, while dopamine induced a similar transient increase in cytoplasmic NOX2 and p47phox expression, in the (peri)nucleus this increased expression persisted for 48 hours, where it co-localized with ROS. Conclusion(s): Exposure of H9C2 cells to elevated dopamine levels induced lipid accumulation, oxidative stress and a pro-inflammatory status of the plasma membrane. This can, in part, explain the inflammatory response in patients with stress-induced heart failure.
- Pro-inflammatory status
- lipid accumulation
- Copyright © 2015, American Journal of Physiology-Heart and Circulatory Physiology