A Role for Superoxide in Protein Kinase C Activation and Induction of Long-term Potentiation*
- From the ‡Department of Neuroscience and the§Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 and the‖Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
Abstract
The induction of several forms of long-term potentiation (LTP) of synaptic transmission in the CA1 region of the mammalian hippocampus is dependent onN-methyl-d-aspartate receptor activation and the subsequent activation of protein kinase C (PKC), but the mechanisms that underlie the regulation of PKC in this context are largely unknown. It is known that reactive oxygen species, including superoxide, are produced byN-methyl-d-aspartate receptor activation in neurons, and recent studies have suggested that some reactive oxygen species can modulate PKC in vitro. Thus, we have investigated the role of superoxide in both the induction of LTP and the activation of PKC during LTP. We found that incubation of hippocampal slices with superoxide scavengers inhibited the induction of LTP. The effects of superoxide on LTP induction may involve PKC, as we observed that superoxide was required for appropriate modulation of PKC activation during the induction of LTP. In this respect, superoxide appears to work in conjunction with nitric oxide, which was required for a portion of the LTP-associated changes in PKC activity as well. Our observations indicate that superoxide and nitric oxide together regulate PKC in a physiologic context and that this type of regulation occurs during the induction of LTP in the hippocampus.
Footnotes
-
↵* This work was supported by National Institutes of Health Grants NS08950 (to E. K.), NS34007 (to E. K.), and MH48186 (to J. D. S.), National Institutes of Health Training Grant MH18273 (to L. T. K.), a University of Pittsburgh CRDF Award (to E. K.), grants from the McKnight Foundation (to J. D. S.), the Winters Foundation (to E. K.), and the Life and Health Insurance Medical Research Fund (to E. D. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵¶ To whom correspondence should be addressed: Dept. of Neuroscience, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, PA 15260. Tel.: 412-624-4610; Fax: 412-624-9198; E-mail:klann{at}brain.bns.pitt.edu.
-
↵1 The abbreviations used are: LTP, long-term potentiation; HFS, high frequency stimulation; NMDA,N-methyl-d-aspartate; PKC, protein kinase C; ROS, reactive oxygen species; SOD, superoxide dismutase; DMPO, 5,5-dimethylpyrroline 1-oxide; EPSP, excitatory postsynaptic potential; NOS, nitric oxide synthase; NO, nitric oxide; NOArg,N-nitro-arginine.
-
↵2 L. T. Knapp and E. Klann, unpublished observations.
-
↵3 J. D. Sweatt, C. M. Atkins, J. D. English, E. D. Roberson, and E. Klann, unpublished observations.
-
- Received March 5, 1997.
- Revision received November 6, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
