Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro.
作者： Katharina Leitmeyer , Andrea Glutz , Vesna Radojevic , Cristian Setz , Nathan Huerzeler
DOI: 10.1155/2015/925890
关键词:
摘要: Rapamycin is an antifungal agent with immunosuppressive properties. inhibits the mammalian target of rapamycin (mTOR) by blocking mTOR complex 1 (mTORC1). atypical serine/threonine protein kinase, which controls cell growth, proliferation, and metabolism. However, less known about pathway in inner ear. First, we evaluated whether or not two complexes (mTORC1 mTORC2, resp.) are present cochlea. Next, tissue explants 5-day-old rats were treated increasing concentrations to explore effects on auditory hair cells spiral ganglion neurons. Auditory survival, neuron number, length neurites, neuronal survival analyzed vitro. Our data indicates that both expressed We observed inhibition results a dose dependent damage cells. Moreover, neurite number neurites significantly decreased all used compared control manner. indicate may play role modulates outgrowth formation.
hindawi.com
core.ac.uk参考文章(34)
Alex Gutierrez-Dalmau, Josep M Campistol, Immunosuppressive therapy and malignancy in organ transplant recipients: a systematic review. Drugs. ,vol. 67, pp. 1167- 1198 ,(2007) , 10.2165/00003495-200767080-00006
Slapnick Sm, Sobkowicz Hm, Loftus Jm, Tissue culture of the organ of Corti. Acta Oto-laryngologica. ,vol. 502, pp. 3- 36 ,(1993)
Na Cai, Ning-Ning Liu, Lei Chen, Ning Zhao, Li-Min Liu, Shun-Dong Dai, PI3K/AKT/mTOR signaling pathway inhibitors in proliferation of retinal pigment epithelial cells International Journal of Ophthalmology. ,vol. 5, pp. 675- 680 ,(2012) , 10.3980/J.ISSN.2222-3959.2012.06.05
BÖRje Drettner, Carl-Magnus Eneroth, Acute otitis media; comparative therapeutic results of sulphonamide and penicillin administered in various forms. Acta Oto-laryngologica. ,vol. 113, pp. 1- 79 ,(1993) , 10.3109/00016489309135758
Mireille Montcouquiol, Jeffrey T. Corwin, Intracellular signals that control cell proliferation in mammalian balance epithelia: key roles for phosphatidylinositol-3 kinase, mammalian target of rapamycin, and S6 kinases in preference to calcium, protein kinase C, and mitogen-activated protein kinase. The Journal of Neuroscience. ,vol. 21, pp. 570- 580 ,(2001) , 10.1523/JNEUROSCI.21-02-00570.2001
Bin Fang, Hongjun Xiao, Rapamycin alleviates cisplatin-induced ototoxicity in vivo Biochemical and Biophysical Research Communications. ,vol. 448, pp. 443- 447 ,(2014) , 10.1016/J.BBRC.2014.04.123
Sathish Kumar Mungamuri, XiaoHe Yang, Ann D. Thor, Kumaravel Somasundaram, Survival Signaling by Notch1: Mammalian Target of Rapamycin (mTOR)–Dependent Inhibition of p53 Cancer Research. ,vol. 66, pp. 4715- 4724 ,(2006) , 10.1158/0008-5472.CAN-05-3830
Lisa M. Ballou, Richard Z. Lin, Rapamycin and mTOR kinase inhibitors Journal of Chemical Biology. ,vol. 1, pp. 27- 36 ,(2008) , 10.1007/S12154-008-0003-5
Tina Huang, Alan G. Cheng, Howard Stupak, Wei Liu, Ana Kim, Hinrich Staecker, Philippe P. Lefebvre, Brigitte Malgrange, Richard Kopke, Gustave Moonen, Thomas R. Van De Water, Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies International Journal of Developmental Neuroscience. ,vol. 18, pp. 259- 270 ,(2000) , 10.1016/S0736-5748(99)00094-5
J. Halloran, S.A. Hussong, R. Burbank, N. Podlutskaya, K.E. Fischer, L.B. Sloane, S.N. Austad, R. Strong, A. Richardson, M.J. Hart, V. Galvan, Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience. ,vol. 223, pp. 102- 113 ,(2012) , 10.1016/J.NEUROSCIENCE.2012.06.054