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Title of Journal: Arch Toxicol

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Abbravation: Archives of Toxicology

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Springer Berlin Heidelberg

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DOI

10.1016/0378-7753(95)02235-x

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1432-0738

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Ceramide/sphingomyelin cycle involvement in gentam

Authors: Le Nguyen Uyen Chi Keiji Tabuchi Mariko Nakamagoe Masahiro Nakayama Bungo Nishimura Akira Hara
Publish Date: 2014/05/06
Volume: 89, Issue: 3, Pages: 415-421
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Abstract

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 gentamicininduced 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 2hydroxyoleic acid a sphingomyelin synthase activator and myriocin a serine palmitoyltransferase inhibitor Hair cell loss was significantly decreased in the presence of GW4869 or 2hydroxyoleic acid Myriocin had no significant effects against gentamicininduced 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 gentamicininduced ototoxicity

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