title: Sensory neurons respond to hypoxia with NO production associated with mitochondria.
abstract: Oxygen is pivotal for mammalian cell function, and recent studies suggest an involvement of NO in cellular adaptation to low oxygen supply. Here, we report that endothelial NO-synthase is ubiquitously expressed in rat and mice sensory neurons, and is targeted to juxtamitochondrial compartments of the ER. There it is activated in response to hypoxia while generation of reactive oxygen species remains unaltered. Developing a technique for ultrastructural localization of an NO-sensitive indicator allowed to identify the inner mitochondrial membrane as the target of NO under hypoxia. The demonstrated hypoxic stimulation of endothelial NOS in sensory neurons shall contribute to resistance against hypoxia, since NO promotes cellular survival by interfering with mitochondrial function.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Justus-Liebig-University, D-35385 Giessen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Henrich
authors.forename: Karin
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Peter
authors.initials: P
authors.lastname: König
authors.forename: Marco
authors.initials: M
authors.lastname: Gruss
authors.forename: Tamara
authors.initials: T
authors.lastname: Fischbach
authors.forename: Axel
authors.initials: A
authors.lastname: Gödecke
authors.forename: Gunter
authors.initials: G
authors.lastname: Hempelmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D018871:Endoplasmic Reticulum, Smooth / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019793:Fluorescein / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron / Q000379:methods; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D009924:Organ Culture Techniques; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C111205:4,5-diaminofluorescein; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D020030:Nitric Oxide Donors; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D012402:Rotenone; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D013755:Tetradecanoylphorbol Acetate; D019793:Fluorescein