Vector-mediated delivery of bcl-2 prevents degeneration of auditory hair cells and neurons after injury.

Adenoviridae; Animals; Animals, Newborn; Apoptosis/genetics; Brain-Derived Neurotrophic Factor/pharmacology; Cell Survival; Cells, Cultured; Cisplatin/toxicity; Genes, bcl-2/physiology; Genetic Vectors; Hair Cells, Auditory/drug effects/pathology; Membrane Potential, Mitochondrial/drug effects/genetics; Neomycin/toxicity; Nerve Degeneration/genetics; Neurons/drug effects/pathology; Oxidative Stress; Rats; Rats, Wistar; Simplexvirus; Spiral Ganglion/drug effects/pathology

Abstract :

[en] OBJECTIVE: To test the hypothesis that bcl-2 prevents oxidative stress-induced apoptosis of auditory sensory cells in explants of the organ of Corti and dissociated cell cultures of the spiral ganglion. METHODS: Organ of Corti explants and dissociated spiral ganglion cell cultures obtained from 3-day-old (P3) rats or adult spiral ganglion cell cultures from 28-day-old (P28) rats were transduced with vectors containing a human bcl-2 gene. Cultures were then exposed to neomycin, cisplatin or subjected to withdrawal of neurotrophin supplementation. Outcome measures included hair cell and neuron counts, mitochondrial membrane potential and a histological measure of apoptosis. RESULTS: Expression of bcl-2 in the organ of Corti explants and neuronal cell cultures provided a significant level of protection against cell death. Bcl-2 expression in the organ of Corti explants also protected mitochondria from loss of membrane potential and blocked an early step in the commitment of hair cells to apoptosis. CONCLUSION: Expression of bcl-2 in cochlear tissues protects sensory cells from a variety of insults that have been demonstrated to damage the inner ear.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Staecker, Hinrich

Liu, Wei

Malgrange, Brigitte ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. - Neurologie

Lefèbvre, Philippe ; Université de Liège - ULiège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie

Van De Water, Thomas R

Language :

English

Title :

Vector-mediated delivery of bcl-2 prevents degeneration of auditory hair cells and neurons after injury.

Publication date :

2007

Journal title :

ORL

ISSN :

0301-1569

eISSN :

1423-0275

Publisher :

Karger, Basel, Switzerland

Volume :

Issue :

Pages :

43-50

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 November 2009

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Bibliography

Lefebvre PP, Malgrange B, Lallemend F, Staecker H, Moonen G, Van de Water TR: Mechanisms of cell death in the injured auditory system: otoprotective strategies. Audiol Neurootol 2002;7:165-170.
Katoh S, Mitsui Y, Kitani K, and Suzuki T: The rescuing effect of nerve growth factor is the result of up-regulation of bcl-2 in hyperoxia-induced apoptosis of a subclone of pheochromocytoma cells, PC12h. Neurosci Lett 1997;232:71-74.
Deng G, Su JH, Ivins KJ, Van Houten B, Cotman CW: Bcl-2 facilities recovery from DNA damage after oxidative stress. Exp Neurol 1999;159:309-318.
Deshmukh M, Johnson EM Jr: Programmed cell death in neurons: focus on the pathway of nerve growth factor deprivation-induced death of sympathetic neurons. Mol Pharmacol 1997;51:897-906.
Knudson CM, Korsmeyer SJ: Bcl-2 and Bax function independently to regulate cell death. Nat Genet 1997;16:358-363.
Middleton G, Wyatt S, Cox A, Korsmeyer S, Davies AM: Differences in Bcl-2 and Bax-independent function in regulating apoptosis in sensory neuron populations. Eur J Neurosci 2000;12:819-827.
Furukawa K, Estus S, Fu W, Mark RJ, Mattson MP: Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways. J Cell Biol 1997;136:1137-1149.
Rong P, Bennie AM, Epa WR, Barrett GL: Nerve growth factor determines survival and death of PC12 cells by regulation of the bcl-x, bax, and caspase-3 genes. J Neurochem 1999;72:2294-2300.
Deshmukh M, Johnson EM Jr: Programmed cell death in neurons: focus on the pathway of nerve growth factor deprivation-induced death of sympathetic neurons. Mol Pharmacol 1997;51:897-906.
Kaufmann JA, Bickford PC, Taglialatela G: Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fisher-344 rats. J Neurochem 2001;76:1099-1108.
Lee HC, Wei YH: Mitochondrial role in life and death of the cell. J Biomed Sci 2000;7:2-15.
Murphy AN, Fiskum G, Beal MF: Mitochondria in neurodegeneration: bioenergetic function in cell death. J Cereb Blood Flow Metab 1999;19:231-245.
Lawrence MS, McLaughlin JR, Sun GH, Ho DY, McIntosh L, Kunis DM, Sapolsky RM, Steinberg GK: Herpes simplex viral vectors expressing Bcl-2 are neuroprotective when delivered after a stroke. J Cereb Blood Flow Metab 1997;17:740-744.
Saavedra RA, Murray M, de Lacalle S, Tessler A: In vivo neuroprotection of injured CNS neurons by a single injection of a DNA plasmid encoding the Bcl-2 gene. Prog Brain Res 2000;128:365-372.
Zhao H, Yenari MA, Cheng D, Sapolsky RM, Steinberg GK: Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. J Neurochem 2003;85:1026-1036.
Malgrange B, Rigo JM, Coucke P, Thiry M, Hans G, Nguyen L, van de Water TR, Moonen G, Lefebvre PP: Identification of factors that maintain mammalian outer hair cells in adult organ of Corti explants. Hear Res 2002;170:48-58.
Lefebvre PP, Staecker H, Moonen G, Van De Water TR: Naftidrofuryl affects neurite regeneration by injured adult auditory neurons. Acta Otolaryngol 1993;113:498-501.
Lefebvre PP, Van De Water TR, Staecker H, Weber T, Galinovic-Schwartz V, Moonen G, Ruben RJ: Nerve growth factor stimulates neurite regeneration but not survival of adult auditory neurons in vitro. Acta Otolaryngol 1992;112:288-293.
Liu W, Staecker H, Stupak H, Malgrange B, Lefebvre P, Van De Water TR: Caspase inhibitors prevent cisplatin-induced apoptosis of auditory sensory cells. Neuroreport 1998;9:2609-2614.
Staecker H, Galinovic-Schwartz V, Liu W, Lefebvre P, Kopke R, Malgrange B, Moonen G, Van De Water TR: The role of the neurotrophins in maturation and maintenance of postnatal auditory innervation. Am J Otol 1996;17:486-492.
Fiskum G, Murphy AN, Beal MF: Mitochondria in neurodegeneration: acute ischemia and chronic neurodegenerative diseases. J Cereb Blood Flow Metab 1999;19:351-369.
Bennett J, Zeng Y, Bajwa R, Klatt L, Li Y, Maguire AM: Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Gene Ther 1998;5:1156-1164.
Lawrence MS, McLaughlin JR, Sun GH, Ho DY, McIntosh L, Kunis DM, Sapolsky RM, Steinberg GK: Herpes simplex viral vectors expressing Bcl-2 are neuroprotective when delivered after a stroke. J Cereb Blood Flow Metab 1997;17:740-744.
Linnik MD, Zahos P, Geschwind MD, Federoff HJ. Expression of bcl-2 from a defective herpes simplex virus-1 vector limits neuronal death in focal cerebral ischemia. Stroke 1995;26:1670-1674.
Matsuoka N, Yukawa H, Ishii K, Hamada H, Akimoto M, Hashimoto N, Miyatake S: Adenovirus-mediated gene transfer of Bcl-xL prevents cell death in primary neuronal culture of the rat. Neurosci Lett 1999;270:177-180.
Shimazaki K, Urabe M, Monahan J, Ozawa K, Kawai N: Adeno-associated virus vector-mediated bcl-2 gene transfer into post-ischemic gerbil brain in vivo: prospects for gene therapy of ischemia-induced neuronal death. Gene Ther 2000;7:1244-1249.
Zhao H, Yenari MA, Cheng D, Sapolsky RM, Steinberg GK: Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. J Neurochem 2003;85:1026-1036.