Maturation of cochlear glutathione-S-transferases correlates with the end of the sensitive period for ototoxicity

Donna S Whitlon*, Lynda S. Wright, Shelli A. Nelson, Renee Szakaly, Frank L. Siegel

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The developing mammalian cochlea is especially sensitive to chemical toxins. In rats, the period of increased sensitivity falls roughly between postnatal days (P) 8 and 28. One unexplored hypothesis for this 'sensitive period' is that young cochleas may have immature complements of detoxification enzymes. Glutathione-S-transferases (GSTs) are a family of detoxification enzymes which catalyze the conjugation of many xenobiotics to glutathione. Using high performance liquid chromatography (HPLC), we measured the concentrations of soluble GST isoforms in cochleas of developing Fischer 344 rats. At P1, the concentration of isoform rGSTP1 was 9 pmol/mg protein. That of the remaining isoforms studied was low, <2 pmol/mg protein, and, except for rGSTA3, remained so throughout the period of study. At P2, immunolabelling visualized rGSTP1 in the stria vascularis, Reissner's membrane, spiral limbus and organ of Corti. From P1 to P28, rGSTP1 increased to 15 pmol/mg protein and was detected additionally in satellite cells of the spiral ganglion and in the spiral ligament. From P7 to P28, rGSTA3 increased 8-fold (3-24 pmol/mg protein), became the predominant isoform in the adult organ and localized to pillar cells, the limbus and the spiral ligament. In the vestibule, rGSTP1 predominated, although rGSTA3 increased slightly over time. These observations suggest that biochemical immaturity in detoxification enzymes in the cochlea may contribute to the increased sensitivity to ototoxins during development and that differences in detoxification enzymes between cells in the cochlea and between inner ear organs may underlie differences in susceptibility to ototoxins.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalHearing Research
Volume137
Issue number1-2
DOIs
StatePublished - Nov 1 1999

Fingerprint

Cochlea
Glutathione Transferase
Protein Isoforms
Spiral Ligament of Cochlea
Organ of Corti
Enzymes
Proteins
Stria Vascularis
Spiral Ganglion
Inbred F344 Rats
Xenobiotics
Inner Ear
Glutathione
High Pressure Liquid Chromatography
Membranes

Keywords

  • Cochlea
  • Detoxification
  • Development
  • Glutathione-S-transferase
  • Ototoxicity
  • Vestibular system

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Whitlon, Donna S ; Wright, Lynda S. ; Nelson, Shelli A. ; Szakaly, Renee ; Siegel, Frank L. / Maturation of cochlear glutathione-S-transferases correlates with the end of the sensitive period for ototoxicity. In: Hearing Research. 1999 ; Vol. 137, No. 1-2. pp. 43-50.
@article{fc07141718794234be0819454b94e11c,
title = "Maturation of cochlear glutathione-S-transferases correlates with the end of the sensitive period for ototoxicity",
abstract = "The developing mammalian cochlea is especially sensitive to chemical toxins. In rats, the period of increased sensitivity falls roughly between postnatal days (P) 8 and 28. One unexplored hypothesis for this 'sensitive period' is that young cochleas may have immature complements of detoxification enzymes. Glutathione-S-transferases (GSTs) are a family of detoxification enzymes which catalyze the conjugation of many xenobiotics to glutathione. Using high performance liquid chromatography (HPLC), we measured the concentrations of soluble GST isoforms in cochleas of developing Fischer 344 rats. At P1, the concentration of isoform rGSTP1 was 9 pmol/mg protein. That of the remaining isoforms studied was low, <2 pmol/mg protein, and, except for rGSTA3, remained so throughout the period of study. At P2, immunolabelling visualized rGSTP1 in the stria vascularis, Reissner's membrane, spiral limbus and organ of Corti. From P1 to P28, rGSTP1 increased to 15 pmol/mg protein and was detected additionally in satellite cells of the spiral ganglion and in the spiral ligament. From P7 to P28, rGSTA3 increased 8-fold (3-24 pmol/mg protein), became the predominant isoform in the adult organ and localized to pillar cells, the limbus and the spiral ligament. In the vestibule, rGSTP1 predominated, although rGSTA3 increased slightly over time. These observations suggest that biochemical immaturity in detoxification enzymes in the cochlea may contribute to the increased sensitivity to ototoxins during development and that differences in detoxification enzymes between cells in the cochlea and between inner ear organs may underlie differences in susceptibility to ototoxins.",
keywords = "Cochlea, Detoxification, Development, Glutathione-S-transferase, Ototoxicity, Vestibular system",
author = "Whitlon, {Donna S} and Wright, {Lynda S.} and Nelson, {Shelli A.} and Renee Szakaly and Siegel, {Frank L.}",
year = "1999",
month = "11",
day = "1",
doi = "10.1016/S0378-5955(99)00136-7",
language = "English (US)",
volume = "137",
pages = "43--50",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",
number = "1-2",

}

Maturation of cochlear glutathione-S-transferases correlates with the end of the sensitive period for ototoxicity. / Whitlon, Donna S; Wright, Lynda S.; Nelson, Shelli A.; Szakaly, Renee; Siegel, Frank L.

In: Hearing Research, Vol. 137, No. 1-2, 01.11.1999, p. 43-50.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Maturation of cochlear glutathione-S-transferases correlates with the end of the sensitive period for ototoxicity

AU - Whitlon, Donna S

AU - Wright, Lynda S.

AU - Nelson, Shelli A.

AU - Szakaly, Renee

AU - Siegel, Frank L.

PY - 1999/11/1

Y1 - 1999/11/1

N2 - The developing mammalian cochlea is especially sensitive to chemical toxins. In rats, the period of increased sensitivity falls roughly between postnatal days (P) 8 and 28. One unexplored hypothesis for this 'sensitive period' is that young cochleas may have immature complements of detoxification enzymes. Glutathione-S-transferases (GSTs) are a family of detoxification enzymes which catalyze the conjugation of many xenobiotics to glutathione. Using high performance liquid chromatography (HPLC), we measured the concentrations of soluble GST isoforms in cochleas of developing Fischer 344 rats. At P1, the concentration of isoform rGSTP1 was 9 pmol/mg protein. That of the remaining isoforms studied was low, <2 pmol/mg protein, and, except for rGSTA3, remained so throughout the period of study. At P2, immunolabelling visualized rGSTP1 in the stria vascularis, Reissner's membrane, spiral limbus and organ of Corti. From P1 to P28, rGSTP1 increased to 15 pmol/mg protein and was detected additionally in satellite cells of the spiral ganglion and in the spiral ligament. From P7 to P28, rGSTA3 increased 8-fold (3-24 pmol/mg protein), became the predominant isoform in the adult organ and localized to pillar cells, the limbus and the spiral ligament. In the vestibule, rGSTP1 predominated, although rGSTA3 increased slightly over time. These observations suggest that biochemical immaturity in detoxification enzymes in the cochlea may contribute to the increased sensitivity to ototoxins during development and that differences in detoxification enzymes between cells in the cochlea and between inner ear organs may underlie differences in susceptibility to ototoxins.

AB - The developing mammalian cochlea is especially sensitive to chemical toxins. In rats, the period of increased sensitivity falls roughly between postnatal days (P) 8 and 28. One unexplored hypothesis for this 'sensitive period' is that young cochleas may have immature complements of detoxification enzymes. Glutathione-S-transferases (GSTs) are a family of detoxification enzymes which catalyze the conjugation of many xenobiotics to glutathione. Using high performance liquid chromatography (HPLC), we measured the concentrations of soluble GST isoforms in cochleas of developing Fischer 344 rats. At P1, the concentration of isoform rGSTP1 was 9 pmol/mg protein. That of the remaining isoforms studied was low, <2 pmol/mg protein, and, except for rGSTA3, remained so throughout the period of study. At P2, immunolabelling visualized rGSTP1 in the stria vascularis, Reissner's membrane, spiral limbus and organ of Corti. From P1 to P28, rGSTP1 increased to 15 pmol/mg protein and was detected additionally in satellite cells of the spiral ganglion and in the spiral ligament. From P7 to P28, rGSTA3 increased 8-fold (3-24 pmol/mg protein), became the predominant isoform in the adult organ and localized to pillar cells, the limbus and the spiral ligament. In the vestibule, rGSTP1 predominated, although rGSTA3 increased slightly over time. These observations suggest that biochemical immaturity in detoxification enzymes in the cochlea may contribute to the increased sensitivity to ototoxins during development and that differences in detoxification enzymes between cells in the cochlea and between inner ear organs may underlie differences in susceptibility to ototoxins.

KW - Cochlea

KW - Detoxification

KW - Development

KW - Glutathione-S-transferase

KW - Ototoxicity

KW - Vestibular system

UR - http://www.scopus.com/inward/record.url?scp=0032699696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032699696&partnerID=8YFLogxK

U2 - 10.1016/S0378-5955(99)00136-7

DO - 10.1016/S0378-5955(99)00136-7

M3 - Article

VL - 137

SP - 43

EP - 50

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

IS - 1-2

ER -