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Nitric oxide-mediated mitochondrial impairment in neural cells: a role for glucose metabolism in neuroprotection Bolaños, Juan P. García Nogales, Paula Vega Agapito, María Victoria Delgado Esteban, María Cidad Velasco, María Del Pilar Almeida, Angeles Producción Científica Nitric oxide (žNO) is a highly diffusible, short-lived physiological messenger present in the central nervous system (CNS) (Garthwaite et al., 1988) that is synthesised by a family of nitric oxide synthases (NOSs) which catalyze the conversion of arginine to citrulline and žNO (Bredt and Snyder, 1990; Knowles and Moncada, 1994). All CNS cells synthesise žNO (Murphy et al., 1993). Neurones produce žNO by calcium-dependent activation of neuronal, constitutive NOS (nNOS or NOS1), whereas glial cells synthesise žNO in a calcium-independent way that requires previous transcriptional induction of NOS (inducible NOS, iNOS or NOS2) (Galea et al., 1992; Simmons and Murphy, 1992). Astrocytes also synthesise žNO through NNOS activity (Murphy et al., 1990, 1991; Agullo´ andGarcı´a, 1992a,b). A third isoform of NOS (endothelial NOS, eNOS or NOS3) is associated with brain vasculature. In general, žNO participates in the transduction pathway leading to elevations in intracellular cyclic Ł Corresponding author: Dr. Juan P. Bolan˜os, Departamento de Bioquı´mica y Biologı´a Molecular, Universidad de Salamanca, Edificio Departamental, Plaza Doctores de la Reina s=n, 37007 Salamanca, Spain. Tel.: C34-923-294526; Fax: C34-923-294579; E-mail: jbolanos@gugu.usal.es GMP levels (Bredt and Snyder, 1989; Knowles et al., 1989) and therefore participates in cyclic GMP functions (Wang and Robinson, 1997). However, an increasing body of evidence is now arising to suggest that žNO and its most active metabolite, the peroxynitrite anion (ONOO ), may be involved in the regulation of brain energy metabolism. This chapter will specifically focus on the mechanisms involving žNO and ONOO -mediated interference with brain mitochondrial energy production and the modulating role of glutathione in cell energy metabolism. Finally, we discuss recent evidence that strongly suggests the importance of cell glucose utilisation in maintaining glutathione homeostasis and hence in preventing nitric oxide-mediated mitochondrial impairment. 2024-02-02T22:55:37Z 2024-02-02T22:55:37Z 2001 info:eu-repo/semantics/article Progress in Brain Research https://uvadoc.uva.es/handle/10324/65607 10.1016/S0079-6123(01)32094-0 441 454 132 eng https://www.sciencedirect.com/science/article/abs/pii/S0079612301320940?via%3Dihub info:eu-repo/semantics/restrictedAccess Elsevier Elsevier SI