Excitatory Amino Acid Release from Rat Hippocampal Slices as a Consequence of Free‐Radical Formation

Pellegrini‐Giampietro, Domenico E.; Cherici, Giovanna; Alesiani, Marina; Carlà, Vincenzo; Moroni, Flavio

doi:10.1111/j.1471-4159.1988.tb01187.x

Cited by 202 publications

(57 citation statements)

References 24 publications

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“…In addition, the incubation of hippocampal slices with X/XO has been shown to result in a superoxide-dependent increase in the release of glutamate (Pellegrini-Giampietro et al, 1988). Taken together, these data suggest the possibility that X/XO-induced potentiation is expressed presynaptically.…”

Section: Resultssupporting

confidence: 57%

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

Knapp¹,

2002

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Recent evidence suggests that reactive oxygen species (ROS), including superoxide, are not only neurotoxic but function as small messenger molecules in normal neuronal processes such as synaptic plasticity. Consistent with this idea, we show that brief incubation of hippocampal slices with the superoxidegenerating system xanthine/xanthine oxidase (X/XO) produces a long-lasting potentiation of synaptic transmission in area CA1. We found that X/XO-induced potentiation was associated with a persistent superoxide-dependent increase in autonomous PKC activity that could be isolated via DEAE column chromatography. The X/XO-induced potentiation was blocked by the inhibition of PKC, indicating that the superoxidedependent increase in autonomous PKC activity was necessary for the potentiation. We also found that X/XO-induced potentiation and long-term potentiation (LTP) occluded one another, suggesting that these forms of plasticity share similar cellular mechanisms. In further support of this idea, we found that a persistent, superoxide-dependent increase in autonomous PKC activity isolated via DEAE column chromatography also was associated with LTP. Taken together, our findings indicate that X/XO-induced potentiation and LTP share similar cellular mechanisms, including superoxide-dependent increases in autonomous PKC activity. Finally, our findings suggest that superoxide, in addition to its well known role as a neurotoxin, also can be considered a small messenger molecule critical for normal neuronal signaling.

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Section: Resultssupporting

confidence: 57%

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

Knapp¹,

2002

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“…Second, activation of other glutamate receptors can produce superoxide through a number of biochemical pathways (37). In addition, superoxide increases the release of glutamate in hippocampal slices (38), which suggests a means by which it might modulate synaptic efficacy. Finally, it is interesting to note that although the intracellular form of Cu/Zn-SOD, SOD1, is abundantly expressed in the dentate gyrus and area CA3 of the hippocampus, it is expressed to a much lesser degree in area CA1, the hippocampal subregion studied herein (39); thus, area CA1 is likely to have less capacity for removal of superoxide, consistent with a physiologic role for superoxide in this region.…”

Section: Discussionmentioning

confidence: 99%

A Role for Superoxide in Protein Kinase C Activation and Induction of Long-term Potentiation

Klann¹,

Roberson²,

Knapp³

et al. 1998

Journal of Biological Chemistry

199

150

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The induction of several forms of long-term potentiation (LTP) of synaptic transmission in the CA1 region of the mammalian hippocampus is dependent on N-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 by N-methyl-Daspartate 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. Hippocampal long-term potentiation (LTP)1 is a long-lasting synaptic enhancement that may be involved in certain types of mammalian learning and memory (1). It generally is agreed that in area CA1 of the hippocampus the induction of most forms of LTP induced by high frequency stimulation (HFS) is dependent on Ca 2ϩ entry into the postsynaptic neuron triggered by N-methyl-D-aspartate (NMDA) receptor activation (2-4). The exact biochemical sequence of events following Ca 2ϩ influx into the postsynaptic cell is unknown, but it is clear that Ca 2ϩ -dependent protein kinases are involved in the induction of LTP (5, 6). The activation of protein kinase C (PKC) is one of the requisite biochemical steps necessary for the induction of LTP, as selective PKC inhibitors can block induction of LTP (5,7,8). Furthermore, both the second messenger-independent activity of PKC (autonomous activity; see Ref. 9) and total, cofactor-stimulated PKC activity (cofactor-dependent activity; see Refs. 9 and 10) are increased shortly after LTP-inducing HFS. Mechanisms that have been proposed for the activation of PKC immediately following the induction of LTP (15 s to 2 min after the final HFS) include translocation of PKC to the membrane (11, 12), conformational changes in PKC that result in the unmasking of activator sites (10), and decreases in protein phosphatase activity that might result in increased phosphorylation and activity of PKC (10).An additional mechanism that might be involved in the activation of PKC during the induction of LTP is an oxidative mechanism involving reactive oxygen species (ROS), particularly the superoxide anion (O 2 . ). A variety of evidence suggest this possibility. First, levels of superoxide may in...

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“…There is increasing evidence that glutamate may be a major mediator of oxidative stress in the CNS, primarily through its activation of ionotropic receptors, distinguished by specific agonists. Activation of glutamate receptors by these agonists in tissue culture leads to neuronal degeneration (94,95 (96,97). Furthermore, NO released in the above process interferes with many events, including oxidative phosphorylation, with a reduction in ribonucleotide reductase activity (98) and with forma-KAIAMPA PReceptor Na' tion of OH from 02 (99), ultimately leading to degeneration of neurons (100).…”

Section: Age-related Degenerative Diseases and Defects In Oxidative Pmentioning

confidence: 99%

The development of mitochondrial medicine.

Luft¹

1994

Proc. Natl. Acad. Sci. U.S.A.

270

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Primary defects in mitochondrial function are implicated in over 100 diseses, and the list continues to grow. Yet the first mitochondrial defect-a myopathy-was demonstrated only 35 years ago. The field's dramatic expansion reflects growth of knowledge in three areas: (i) characterization of mitochondrial structure and function, (i) euiation of the steps involved in mitochondrial biosynthesis, and (Ni) discovery of specific mitochondrial DNA. Many mitochondrial diseases are accompanied by mutations in this DNA. Inheritance is by maternal t ission. The metabolic defects encompass the electron transport complexes, intermediates of the tricarboxylic acid cycle, and substrate transport. The clinical manifestations are protean, most often involving skeletal muscie and the central nervous system. In addition to being a primary cause of disease, mitochondrial DNA mutations and impaired oxidation have now been found to occur as secondary phenomena in aging as weli as in age-related degenerative diseases such as Parkinson, Alzheimer, and Huntington diseases, amyotrophic lateral sclerosis and cardiomyopathies, atherosclerosis, and diabetes meflitus. Manifestations of both the primary and secondary mitochondrial diseases are thought to result from the production of oxygen free radicals. With increased understanding of the mechanisms underlying the mitochondrial dysfunctions has come the beginnings of therapeutic sttegies, based mostly on the administration of antioxidants, replacement of cofactors, and provision of nutrients. At the present accelerating pace of development of what may be cafled mitochondrial medicine, much more is likely to be achieved within the next few years.In 1959, the first biochemical studies of a cell organelle in humans were undertaken, following observations made at the bedside of a patient with striking symptoms, never before encountered. These clinical observations, first, led to an idea about the origin ofthe symptoms and, second, to studies of the particular organelle: the mitochondrion (1). The pathophysiology of the mitochondria developed gradually over the years as relevant discoveries were made in biochemistry, cell biology, and molecular biology. During the past few years the field mitochondrial medicine has expanded dramatically, in several directions. I here provide a short review concentrating on those aspects most relevant to clinical medicine. In the accompanying review (174), Wallace describes the molecular, biological, and evolutionary implications of mitochondrial diseases.The Birth of Mitochondrial Medicine (1959)(1960)(1961)(1962): Luft DiseaseThe first patient found to have a mitochondrial disease was a 30-year-old woman who developed clinical symptoms at the age of 7. Her dominant symptoms were enormous perspiration combined with markedly increased fluid intake but without polyuria; extremely high caloric intake (above 3000 kcal per day) at a stable body weight of 38 kg and a body height of 159 cm; and general weakness, particularly prominent in her musculature. The do...

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Excitatory Amino Acid Release from Rat Hippocampal Slices as a Consequence of Free‐Radical Formation

Cited by 202 publications

References 24 publications

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

A Role for Superoxide in Protein Kinase C Activation and Induction of Long-term Potentiation

The development of mitochondrial medicine.

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