NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1
Version of Record online: 9 MAY 2005
Journal of Neurochemistry
Volume 94, Issue 2, pages 299–306, July 2005
How to Cite
Kishida, K. T., Pao, M., Holland, S. M. and Klann, E. (2005), NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. Journal of Neurochemistry, 94: 299–306. doi: 10.1111/j.1471-4159.2005.03189.x
- Issue online: 16 MAY 2005
- Version of Record online: 9 MAY 2005
- Received December 20, 2004; revised manuscript received March 14, 2005; accepted March 16, 2005.
- learning and memory;
- long-term potentiation;
- oxygen species;
Previous studies have shown that N-methyl-d-aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor-dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor-dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N-acetyl-l-cysteine (L-NAC), the superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor-dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47phox, one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1.