An assessment of the role of reactive oxygen species and redox signaling in norepinephrine-induced apoptosis and hypertrophy of H9c2 cardiac myoblasts

作者：Gupta MK; Neelakantan TV; Sanghamitra M; Tyagi RK; Dinda A; Maulik S; Mukhopadhyay CK; Goswami SK^*

来源：Antioxidants and Redox Signaling, 2006, 8(5-6): 1081-1092.

DOI：10.1089/ars.2006.8.1081

Cardiac myocytes, upon exposure to increasing doses of norepinephrine (NE), transit from hypertrophic to apoptotic phenotype. Since reactive oxygen species (ROS) generation is attributed to both phenomena, the authors tested whether an elevation in intracellular ROS level causes such transition. H9c2 cardiac myoblasts upon treatment with hypertrophic and apoptotic doses of NE (2 and 100 mu M, respectively) transiently induced intracellular ROS at a comparable level, while 200 mu M H2O2, another proapoptotic agonist, showed robust and sustained ROS generation. Upon analysis of a number of redox-responsive transcription factors as the downstream targets of ROS signaling, the authors observed that NE (2 and 100 PM) and H2O2 (200 mu M) were ineffective in inducing NF-KB while both the agonists upregulated AP-1 and Nrf-2. However, the extents of induction of AP-1 and Nrf-2 were not in direct correlation with the respective ROS levels. Also, AP-1 activities induced by two doses of NE were intrinsically different, since at 2 mu M, it primarily induced FosB, and at 100 mu M it activated Fra-1. Differential induction of FosB and Fra-1 was also reiterated in adult rat myocardium injected with increasing doses of NE. Therefore, NE induces hypertrophy and apoptosis in cardiac myocytes by distinct redox-signaling rather than a general surge of ROS.

• 出版日期2006-6
• 单位河北医科大学