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Glutamate triggers neurosecretion and apoptosis in bovine chromaffin cells through a mechanism involving NO production by neuronal NO synthase activation

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Pérez Rodríguez, Rocío and Oliván, A. M. and Roncero Romero, César and Morón Oset, J. and González Prieto, María Pilar and Oset Gasque, María Jesús (2014) Glutamate triggers neurosecretion and apoptosis in bovine chromaffin cells through a mechanism involving NO production by neuronal NO synthase activation. Free Radical Biology and Medicine, 69 . pp. 390-402. ISSN 0891-5849

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Official URL: http://dx.doi.org/10.1016/j.freeradbiomed.2014.01.029




Abstract

Previous work from our group stated that nitric oxide (NO), via cytokines, induces apoptosis in chromaffin cells by a mechanism involving iNOS, nNOS, and NF-κB. In this paper the involvement of glutamate as a possible intracellular trigger of neurosecretion and NO-mediated apoptosis has been evaluated. We show that chromaffin cells express different ionotropic and metabotropic glutamate receptors, this exerting different effects on the regulation of basal and glutamate-induced catecholamine secretion, via NO/cGMP. In addition, we studied the effects of endogenously generated NO, both basal and glutamate-stimulated, on apoptosis of chromaffin cells. Our results show that glutamate agonists are able to induce cell death and apoptosis in bovine chromaffin cells, parallel to an increase in NO production. Such effects were reversed by NOS inhibitors and glutamate receptor antagonists. Under basal conditions, iNOS inhibitors did not have any effect on apoptosis, whereas nNOS inhibitors induced apoptosis, indicating a neuroprotective effect of constitutive nNOS-generated NO. In contrast, glutamate-induced apoptosis was strongly reversed by nNOS inhibitors and weakly by iNOS inhibitors, thus indicating nNOS involvement in glutamate-mediated apoptosis. These results were confirmed by the fact that nNOS expression, but not iNOS, is specifically activated by glutamate. Finally, our results suggest the participation of PKG, PKA, PKC, and MAPK pathways in glutamate-mediated nNOS activation in chromaffin cells and point out the involvement of both PKA and PKC signaling pathways in the apoptotic effect of glutamate.


Item Type:Article
Uncontrolled Keywords:Glutamate, Nitric oxide, Nitric oxide synthase, Cell death, Chromaffin cells, Apoptosis, Signal transduction, NF-κB, Free radicals
Subjects:Medical sciences > Pharmacy > Biochemistry
ID Code:32460
Deposited On:27 Jul 2015 08:30
Last Modified:04 Aug 2015 10:21

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