title: High expression of cytochrome b 5 reductase isoform 3/cytochrome b 5 system in the cerebellum and pyramidal neurons of adult rat brain.
abstract: Cytochrome b 5 reductase (Cb 5R) and cytochrome b 5 (Cb 5) form an enzymatic redox system that plays many roles in mammalian cells. In the last 15 years, it has been proposed that this system is involved in the recycling of ascorbate, a vital antioxidant molecule in the brain and that its deregulation can lead to the production of reactive oxygen species that play a major role in oxidative-induced neuronal death. In this work, we have performed a regional and cellular distribution study of the expression of this redox system in adult rat brain by anti-Cb 5R isoform 3 and anti-Cb 5 antibodies. We found high expression levels in cerebellar cortex, labeling heavily granule neurons and Purkinje cells, and in structures such as the fastigial, interposed and dentate cerebellar nuclei. A large part of Cb 5R isoform 3 in the cerebellum cortex was regionalized in close proximity to the lipid raft-like nanodomains, labeled with cholera toxin B, as we have shown by fluorescence resonance energy transfer imaging. In addition, vestibular, reticular and motor nuclei located at the brain stem level and pyramidal neurons of somatomotor areas of the brain cortex and of the hippocampus have been also found to display high expression levels of these proteins. All these results point out the enrichment of Cb 5R isoform 3/Cb 5 system in neuronal cells and structures of the cerebellum and brain stem whose functional impairment can account for neurological deficits reported in type II congenital methemoglobinemia, as well as in brain areas highly prone to undergo oxidative stress-induced neurodegeneration.
authors: Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Extremadura, 06006, Badajoz, Spain.
authors: A K
authors: AK
authors: Samhan-Arias
authors: Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, 06006, Badajoz, Spain.
authors: C
authors: C
authors: López-Sánchez
authors: Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Extremadura, 06006, Badajoz, Spain.
authors: D
authors: D
authors: Marques-da-Silva
authors: Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Extremadura, 06006, Badajoz, Spain.|Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, 06006, Badajoz, Spain.|ESTG-Polytechnic Institute of Leiria, Leiria, Portugal.
authors: R
authors: R
authors: Lagoa
authors: Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: V
authors: V
authors: Garcia-Lopez
authors: Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, 06006, Badajoz, Spain.
authors: V
authors: V
authors: García-Martínez
authors: Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Extremadura, 06006, Badajoz, Spain. carlosgm@unex.es.
authors: C
authors: C
authors: Gutierrez-Merino
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D002531:Cerebellum / Q000201:enzymology*; D042966:Cytochrome-B(5) Reductase / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000201:enzymology; D019579:Neocortex / Q000201:enzymology; D009457:Neuroglia / Q000201:enzymology; D017966:Pyramidal Cells / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007527:Isoenzymes; D015786:Cytochromes b5; D042966:Cytochrome-B(5) Reductase
keywords: Brain stem; Cerebellar and vestibular nuclei; Cerebellar granule neurons; Cerebellum; Cytochrome b 5; Cytochrome b 5 reductase isoform 3; Hippocampus; Neocortex; Purkinje neurons; Rat brain