P2X7 receptor-induced generation of reactive oxygen species in rat mesangial cells

Apoptosis of mesangial cells is an important mode of cell death that maintains normal morphology and function within the glomerulus during development and in normal cell turnover; it is also important in pathological processes. Stimulation of rat mesangial cells via P2X(7) receptors can induce apoptotic cell death. However, the signaling pathways are not well understood. Recently, Sub et al. reported P2X(7) receptor-mediated generation of reactive oxygen species (ROS). Generations of ROS have been linked to induction of apoptosis. In this study, we characterized the P2X(7) receptor-induced ROS generation in rat mesangial cells. P2X(7) agonist, 2' and 3'-O-(4-benzoyl) benzoyl-ATP (BzATP) evoked ROS generation in a concentration-dependent manner. The profile of ROS generation in response to BzATP was characteristic of the activation of NADPH oxidase. We could also detect BzATP-induced production of peroxynitrite. These results suggested that the superoxide anion was generated primarily, and then it rapidly reacted with endogenous nitric oxide, yielding peroxynitrite. The generation of ROS in rat mesangial cells may contribute to P2X(7) receptor-induced apoptotic cell death. (C) Wiley-Liss, Inc.