Sensory neurons respond to hypoxia with NO production associated with mitochondria.
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.
Henrich
Michael
M
Department of Anaesthesiology and Intensive Care, Justus-Liebig-University, D-35385 Giessen, Germany.
Hoffmann
Karin
K
König
Peter
P
Gruss
Marco
M
Fischbach
Tamara
T
Gödecke
Axel
A
Hempelmann
Gunter
G
Kummer
Wolfgang
W
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
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