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Phosphoinositide and Erk signaling pathways mediate activity-driven rodent olfactory sensory neuronal survival and stress mitigation
- Phosphoinositide and Erk signaling pathways mediate activity-driven rodent olfactory sensory neuronal survival and stress mitigation
- Kim, So Yeun; Mammen, Alex; Yoo, Seung-Jun; Cho, Bongki; Kim, Eun-Kyoung; Park, Jong-In; Moon, Cheil; Ronnett, Gabriele V.
- DGIST Authors
- Kim, So Yeun; Yoo, Seung-Jun; Cho, Bongki; Kim, Eun-Kyoung; Moon, Cheil
- Issue Date
- Journal of Neurochemistry, 134(3), 486-498
- Article Type
- Activity Driven Survival; Adenovirus Infection; Adenovirus Vector; Adenylyl Cyclase; Adult; Adult Mice; Animal; Animal Cell; Animal Experiment; Animal Model; Animal Tissue; Animals; Blotting, Northern; C57Bl Mouse; Cell Stress; Cell Survival; Cell Survival; Cell Viability; Controlled Study; Cyclic AMP; Dual 2nd Messenger Pathways; Enzyme Activation; Enzyme Activity; Enzyme Inhibition; Enzyme Phosphorylation; Heat Shock Protein 70; Immunoblotting; Immunoblotting; Immunohistochemistry; Immunohistochemistry; In Vitro Study; In Vivo Study; Intracellular Space; Isovaleric Acid; Kinase Pathway; Lipid Hydrolysis; Male; Map Kinase Signaling System; Mice; Mice, Inbred C57BL; Mitochondrial Membrane Potential; Mitogen Activated Protein Kinase; Mitogen Activated Protein Kinase; Mitogen Activated Protein Kinase 1; Mitogen Activated Protein Kinase 3; Mitogen Activated Protein Kinase Kinase 1; Mitogen Activated Protein Kinase Kinase 2; Mouse; Nerve Cell Culture; Non Human; Northern Blotting; Odor; Olfactory; Olfactory Receptor; Olfactory Receptor Neurons; Olfactory Sensory Neuron; Olfactory Stimulation; Olfactory System; Oxidative Stress; Oxidative Stress; Oxidative Stress; Phorbol Ester; Phosphatidylinositide; Phosphatidylinositol; Phosphatidylinositols; Phosphoinositide; Physiology; Priority Journal; Protein Expression; Rat; Rat Hippocampal Neurons; Rats; Rats, Sprague Dawley; Reactive Oxygen Metabolite; Receptor Neurons; Rodentia; Sensory Nerve Cell; Sensory Stimulation; Sensory Transduction; Signal Transduction; Small Interfering Rna; Smell; Sprague Dawley Rat; Superoxide Production; Transgenic Mice; Unilateral Naris Occlusion; Upregulation
- Olfactory sensory neurons (OSNs) are the initial site for olfactory signal transduction. Therefore, their survival is essential to olfactory function. In the current study, we demonstrated that while odorant stimulation promoted rodent OSN survival, it induced generation of reactive oxygen species in a dose- and time-dependent manner as well as loss of membrane potential and fragmentation of mitochondria. The MEK-Erk pathway played a critical role in mediating these events, as its inhibition decreased odorant stimulation-dependent OSN survival and exacerbated intracellular stress measured by reactive oxygen species generation and heat-shock protein 70 expression. The phosphoinositide pathway, rather than the cyclic AMP pathway, mediated the odorant-induced activation of the MEK-Erk pathway. These findings provide important insights into the mechanisms of activity-driven OSN survival, the role of the phosphoinositide pathway in odorant signaling, and demonstrate that odorant detection and odorant stimulation-mediated survival proceed via independent signaling pathways. This mechanism, which permits independent regulation of odorant detection from survival signaling, may be advantageous if not diminished by repeated or prolonged odor exposure. © 2015 International Society for Neurochemistry.
- Blackwell Publishing Ltd
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