Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression

  • Kim, So Yeun (Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST)) ;
  • Yoo, Seung-Jun (Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST)) ;
  • Ronnett, Gabriele V (Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST)) ;
  • Kim, Eun-Kyoung (Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST)) ;
  • Moon, Cheil (Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST))
  • Received : 2015.02.10
  • Accepted : 2015.03.12
  • Published : 2015.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Olfactory stimulation activates multiple signaling cascades in order to mediate activity-driven changes in gene expression that promote neuronal survival. To date, the mechanisms involved in activity-dependent olfactory neuronal survival have yet to be fully elucidated. In the current study, we observed that olfactory sensory stimulation, which caused neuronal activation, promoted activation of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and the expression of Bcl-2, which were responsible for olfactory receptor neuron (ORN) survival. We demonstrated that Bcl-2 expression increased after odorant stimulation both in vivo and in vitro. We also showed that odorant stimulation activated Akt, and that Akt activation was completely blocked by incubation with both a PI3K inhibitor (LY294002) and Akt1 small interfering RNA. Moreover, blocking the PI3K/Akt pathway diminished the odorantinduced Bcl-2 expression, as well as the effects on odorant-induced ORN survival. A temporal difference was noted between the activation of Akt1 and the expression of Bcl-2 following odorant stimulation. Blocking the PI3K/Akt pathway did not affect ORN survival in the time range prior to the increase in Bcl-2 expression, implying that these two events, activation of the PI3K pathway and Bcl-2 induction, were tightly connected to promote post-translational ORN survival. Collectively, our results indicated that olfactory activity activated PI3K/Akt, induced Bcl-2, and promoted long term ORN survival as a result.

Keywords

References

  1. Aliani, M., Udenigwe, C.C., Girgih, A.T., Pownall, T.L., Bugera, J.L., and Eskin, M.N. (2013). Aroma and taste perceptions with Alzheimer disease and stroke. Crit. Rev. Food Sci. Nutr. 53, 760-769. https://doi.org/10.1080/10408398.2011.559557
  2. Bruel-Jungerman, E., Veyrac, A., Dufour, F., Horwood, J., Laroche, S., and Davis, S. (2009). Inhibition of PI3K-Akt signaling blocks exercise-mediated enhancement of adult neurogenesis and synaptic plasticity in the dentate gyrus. PLoS One 4, e7901. https://doi.org/10.1371/journal.pone.0007901
  3. Brunet, A., Datta, S.R., and Greenberg, M.E. (2001). Transcriptiondependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr. Opin. Neurobiol. 11, 297-305. https://doi.org/10.1016/S0959-4388(00)00211-7
  4. Cummings, D.M., Knab, B.R., and Brunjes, P.C. (1997). Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domestica. J. Neurobiol. 33, 429-438. https://doi.org/10.1002/(SICI)1097-4695(199710)33:4<429::AID-NEU7>3.0.CO;2-C
  5. Feldman, D.E., and Brecht, M. (2005). Map plasticity in somatosensory cortex. Science 310, 810-815. https://doi.org/10.1126/science.1115807
  6. Gross, A., McDonnell, J.M. and Korsmeyer, S.J. (1999). BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-1911. https://doi.org/10.1101/gad.13.15.1899
  7. Horwood, J.M., Dufour, F., Laroche, S., and Davis, S. (2006). Signalling mechanisms mediated by the phosphoi-nositide 3- kinase/Akt cascade in synaptic plasticity and memory in the rat. Eur. J. Neurosci. 23, 3375-3384. https://doi.org/10.1111/j.1460-9568.2006.04859.x
  8. Hou, L., and Klann, E. (2004). Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent longterm depression. J. Neurosci. 24, 6352-6361. https://doi.org/10.1523/JNEUROSCI.0995-04.2004
  9. Howlett, E., Lin, C.C., Lavery, W., and Stern, M. (2008). A PI3-kinasemediated negative feedback regulates neuronal excitability. PLoS Genet. 4, e1000277. https://doi.org/10.1371/journal.pgen.1000277
  10. Jaworski, J., Spangler, S., Seeburg, D.P., Hoogenraad, C.C., and Sheng, M. (2005). Control of dendritic arborization by the phosphoinositide-3'-kinase-Akt-mammalian target of rapamycin pathway. J. Neurosci. 25, 11300-11312. https://doi.org/10.1523/JNEUROSCI.2270-05.2005
  11. Jiao, Y., Zhang, C., Yanagawa, Y., and Sun, Q.Q. (2006). Major effects of sensory experiences on the neocortical inhibitory circuits. J. Neurosci. 26, 8691-8701. https://doi.org/10.1523/JNEUROSCI.2478-06.2006
  12. Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685. https://doi.org/10.1038/227680a0
  13. Moon, C., Liu, B.Q., Kim, S.Y., Kim, E.J., Park, Y.J., Yoo, J.Y., Han, H.S., Bae, Y.C., and Ronnett, G.V. (2009). Leukemia inhibitory factor promotes olfactory sensory neuronal survival via phosphoinositide 3-kinase pathway activation and Bcl-2. J. Neurosci. Res. 87, 1098-1106. https://doi.org/10.1002/jnr.21919
  14. Reed, J.C. (1994). Bcl-2 and the regulation of programmed cell death. J. Cell Biol. 124, 1-6. https://doi.org/10.1083/jcb.124.1.1
  15. Ronnett, G.V., and Moon, C. (2002). G proteins and olfactory signal transduction. Annu. Rev. Physiol. 64, 189-222. https://doi.org/10.1146/annurev.physiol.64.082701.102219
  16. Ronnett, G.V., Hester, L.D., and Snyder, S.H. (1991). Primary culture of neonatal rat olfactory neurons. J. Neurosci. 11, 1243-1255.
  17. Ronnett, G.V., Cho, H., Hester, L.D., Wood, S.F., and Snyder, S.H. (1993). Odorants differentially enhance phosphoino-sitide turnover and adenylyl cyclase in olfactory receptor neuronal cultures. J. Neurosci. 13, 1751-1758.
  18. Sale, A., Berardi, N., and Maffei, L. (2014) Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiol. Rev. 94, 189-234. https://doi.org/10.1152/physrev.00036.2012
  19. Shaffer, S.W., and Harrison, A.L. (2007). Aging of the somatosensory system: a translational perspective. Phys. Ther. 87, 193-207. https://doi.org/10.2522/ptj.20060083
  20. Spehr, M., Wetzel, C.H., Hatt, H., and Ache, B.W. (2002). 3- phosphoinositides modulate cyclic nucleotide signaling in olfactory receptor neurons. Neuron 33, 731-739. https://doi.org/10.1016/S0896-6273(02)00610-4
  21. Suh, K.S., Kim, S.Y., Bae, Y.C., Ronnett, G.V., and Moon, C. (2006). Effects of unilateral naris occlusion on the olfactory epithelium of adult mice. Neuroreport 17, 1139-1142. https://doi.org/10.1097/01.wnr.0000224762.54336.7d
  22. Sung, Y.K., Moon, C., Yoo, J.Y., Moon, C., Pearse, D., Pevsner, J., and Ronnett, G.V. (2002). Plunc, a member of the secretory gland protein family, is up-regulated in nasal respiratory epithelium after olfactory bulbectomy. J. Biol. Chem. 277, 12762-12769. https://doi.org/10.1074/jbc.M106208200
  23. Towbin, H., Staehelin, T., and Gordon, J. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellu-lose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA 76, 4350-4354. https://doi.org/10.1073/pnas.76.9.4350
  24. Ukhanov, K., Corey, E.A., Brunert, D., Klasen, K., and Ache, B.W. (2010). Inhibitory odorant signaling in Mammalian olfactory receptor neurons. J. Neurophysiol. 103, 1114-1122. https://doi.org/10.1152/jn.00980.2009
  25. Ukhanov, K., Brunert, D., Corey, E.A., and Ache, B.W. (2011). Phosphoinositide 3-kinase-dependent antagonism in mammalian olfactory receptor neurons. J. Neurosci. 31, 273-280. https://doi.org/10.1523/JNEUROSCI.3698-10.2011
  26. Uranga, R.M., Katz, S., and Salvador, G.A. (2013). Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress. J. Biol. Chem. 288, 19773-19784. https://doi.org/10.1074/jbc.M113.457622
  27. Watt, W.C., Sakano, H., Lee, Z.Y., Reusch, J.E., Trinh, K., and Storm, D.R. (2004). Odorant stimulation enhances survival of olfactory sensory neurons via MAPK and CREB. Neuron 41, 955-967. https://doi.org/10.1016/S0896-6273(04)00075-3
  28. Yang, D., Liu, X., Zhang, R., Cheng, K., Mu, J., Fang, L., and Xie, P. (2011). Increased apoptosis and different regulation of proapoptosis protein bax and anti-apoptosis protein bcl-2 in the olfactory bulb of a rat model of depression. Neurosci. Lett. 504, 18-22. https://doi.org/10.1016/j.neulet.2011.08.046
  29. Youle, R.J., and Strasser, A. (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. 9, 47-59. https://doi.org/10.1038/nrm2308

Cited by

  1. Phosphoinositide-3-Kinase Is the Primary Mediator of Phosphoinositide-Dependent Inhibition in Mammalian Olfactory Receptor Neurons vol.10, 2016, https://doi.org/10.3389/fncel.2016.00097
  2. Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease vol.8, 2016, https://doi.org/10.3389/fnagi.2016.00163
  3. Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells vol.37, pp.11, 2016, https://doi.org/10.1007/s13277-016-5395-1
  4. ) Have Impaired Learning and Memory vol.37, pp.22, 2017, https://doi.org/10.1128/MCB.00245-17
  5. Spheroid Culture of Mammalian Olfactory Receptor Neurons: Potential Applications for a Bioelectronic Nose vol.27, pp.6, 2018, https://doi.org/10.5607/en.2018.27.6.574
  6. Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells vol.7, pp.None, 2015, https://doi.org/10.1038/s41598-017-18178-0
  7. Position Review: Functional Selectivity in Mammalian Olfactory Receptors vol.45, pp.7, 2015, https://doi.org/10.1093/chemse/bjaa046