Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro.
To determine if transforming growth factor alpha (TGF alpha) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10(-3) M) exposure either with or without growth factor pretreatment. After TGF alpha (500 ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGF alpha in organ of Corti explants.
Staecker
H
H
Department of Otolaryngology, Albert Einstein College of Medicine, Bronx, NY, USA.
Dazert
S
S
Malgrange
B
B
Lefebvre
P P
PP
Ryan
A F
AF
Van de Water
T R
TR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism*; D006311:Hearing Disorders / Q000139:chemically induced / Q000517:prevention & control*; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D007120:Immunochemistry; D009355:Neomycin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009925:Organ of Corti / Q000166:cytology / Q000378:metabolism; D010590:Phalloidine; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D016211:Transforming Growth Factor alpha; D010590:Phalloidine; D066246:ErbB Receptors; D009355:Neomycin; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium