Ceramide/sphingomyelin cycle involvement in gentamicin-induced cochlear hair cell death

Ceramide, a sphingolipid metabolite, regulates diverse cellular processes including apoptosis, cell senescence, the cell cycle, and cellular differentiation. Exogenously administered ceramide reportedly increased cochlear hair cell death due to gentamicin-induced ototoxicity. Ceramide is mainly gene...

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Bibliographic Details
Published in:Archives of toxicology 2015-03, Vol.89 (3), p.415-421
Main Authors: Chi, Le Nguyen Uyen, Tabuchi, Keiji, Nakamagoe, Mariko, Nakayama, Masahiro, Nishimura, Bungo, Hara, Akira
Format: Article
Language:English
Subjects:
Aniline Compounds - pharmacology
Animals
Animals, Newborn
Apoptosis
Benzylidene Compounds - pharmacology
Biomedical and Life Sciences
Biomedicine
Biosynthesis
Cell cycle
Cell death
Cell Death - drug effects
Cells, Cultured
Ceramides - biosynthesis
Environmental Health
Fatty Acids, Monounsaturated - pharmacology
Gentamicins - toxicity
Hair Cells, Auditory - drug effects
Hair Cells, Auditory - enzymology
Hair Cells, Auditory - metabolism
Hair Cells, Auditory - pathology
Metabolites
Occupational Medicine/Industrial Medicine
Oleic Acids - pharmacology
Organ Toxicity and Mechanisms
Pharmacology/Toxicology
Rats, Sprague-Dawley
Serine C-Palmitoyltransferase - antagonists & inhibitors
Serine C-Palmitoyltransferase - metabolism
Sphingomyelin Phosphodiesterase - antagonists & inhibitors
Sphingomyelin Phosphodiesterase - metabolism
Sphingomyelins - biosynthesis
Toxicity
Transferases (Other Substituted Phosphate Groups) - antagonists & inhibitors
Transferases (Other Substituted Phosphate Groups) - metabolism
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Summary:Ceramide, a sphingolipid metabolite, regulates diverse cellular processes including apoptosis, cell senescence, the cell cycle, and cellular differentiation. Exogenously administered ceramide reportedly increased cochlear hair cell death due to gentamicin-induced ototoxicity. Ceramide is mainly generated via a ceramide/sphingomyelin cycle by sphingomyelinase and sphingomyelin synthase or via de novo synthesis by serine palmitoyltransferase and ceramide synthase. This study was designed to investigate the possible involvement of neutral sphingomyelinase, sphingomyelin synthase, or serine palmitoyltransferase in hair cell death due to gentamicin. The basal turns of the organ of Corti of Sprague–Dawley rats were dissected on postnatal days 3–5. Cochlear cultures were exposed to media containing 35 μM gentamicin for 48 h to assess the effects of GW4869 (a neutral sphingomyelinase inhibitor), 2-hydroxyoleic acid (a sphingomyelin synthase activator), and myriocin (a serine palmitoyltransferase inhibitor). Hair cell loss was significantly decreased in the presence of GW4869 or 2-hydroxyoleic acid. Myriocin had no significant effects against gentamicin-induced hair cell loss. In addition, neutral sphingomyelinase was activated by gentamicin exposure. The present findings strongly suggest that the ceramide/sphingomyelin cycle plays an important role in the protection of hair cells against gentamicin-induced ototoxicity.
ISSN:0340-5761
1432-0738
DOI:10.1007/s00204-014-1259-x