Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

被引:20
作者
Staecker, H
Dazert, S
Malgrange, B
Lefebvre, PP
Ryan, AF
VandeWater, TR
机构
[1] ALBERT EINSTEIN COLL MED,DEPT OTOLARYNGOL,BRONX,NY 10467
[2] UNIV LIEGE,DEPT HUMAN PHYSIOL & PATHOPHYSIOL,LIEGE,BELGIUM
[3] UNIV CALIF SAN DIEGO,DEPT OTOLARYNGOL,SAN DIEGO,CA 92103
[4] UNIV WURZBURG,DEPT OTOLARYNGOL,WURZBURG,GERMANY
[5] ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10467
关键词
organ of Corti explant; aminoglycoside ototoxicity; growth factor protection; hair cells; calcium levels;
D O I
10.1016/S0736-5748(96)00110-4
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 1997 ISDN.
引用
收藏
页码:553 / 562
页数:10
相关论文
共 38 条
[1]  
BOTTENSTEIN J, 1979, P NATL SCI ACAD SCI, V76, P51
[2]  
CLAPHAM DE, 1994, ANNU REV NEUROSCI, V17, P441
[3]   FORMATION OF A TOXIC METABOLITE FROM GENTAMICIN BY A HEPATIC CYTOSOLIC FRACTION [J].
CRANN, SA ;
HUANG, MY ;
MCLAREN, JD ;
SCHACHT, J .
BIOCHEMICAL PHARMACOLOGY, 1992, 43 (08) :1835-1839
[4]  
EXTON JH, 1990, J BIOL CHEM, V265, P1
[5]   EGF RECEPTOR AFFINITY IS REGULATED BY INTRACELLULAR CALCIUM AND PROTEIN KINASE-C [J].
FEARN, JC ;
KING, AC .
CELL, 1985, 40 (04) :991-1000
[6]   PERTUSSIS TOXIN PREVENTS NEOMYCIN-INDUCED CALCIUM-DEPENDENT ELECTROPHYSIOLOGICAL EFFECTS IN RAT HIPPOCAMPAL SLICES [J].
FRANK, C ;
LONGO, R ;
SAGRATELLA, S .
GENERAL PHARMACOLOGY, 1994, 25 (05) :957-961
[7]   PROTEIN KINASE-C-INDEPENDENT ACTIVATION OF C-JUN AND C-FOS TRANSCRIPTION BY EPIDERMAL GROWTH-FACTOR [J].
FRANKLIN, CC ;
KRAFT, AS .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1134 (02) :137-142
[8]   TEMPORAL PATTERN OF INNERVATION IN THE DEVELOPING MOUSE INNER-EAR - AN IMMUNOCYTOCHEMICAL STUDY OF A 66-KD SUBUNIT OF MAMMALIAN NEUROFILAMENTS [J].
GALINOVICSCHWARTZ, V ;
PENG, D ;
CHIU, FC ;
VANDEWATER, TR .
JOURNAL OF NEUROSCIENCE RESEARCH, 1991, 30 (01) :124-133
[9]   SULFHYDRYL COMPOUNDS AND ANTIOXIDANTS INHIBIT CYTOTOXICITY TO OUTER HAIR-CELLS OF A GENTAMICIN METABOLITE IN-VITRO [J].
GARETZ, SL ;
RHEE, DJ ;
SCHACHT, J .
HEARING RESEARCH, 1994, 77 (1-2) :75-80
[10]  
GRAY EMG, 1996, ASS RES OT 19 MIDW M, P198