The mechanism of pneumolysin-induced cochlear hair cell death in the rat.

Maryline Beurg, Aziz Hafidi, Liam Skinner, Graeme Cowan, Yannick Hondarrague, Tim J. Mitchell, Didier Dulon
The Journal of Physiology. 2005-09-28; 568(1): 211-227
DOI: 10.1113/jphysiol.2005.092478

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1. J Physiol. 2005 Oct 1;568(Pt 1):211-27. Epub 2005 Jul 28.

The mechanism of pneumolysin-induced cochlear hair cell death in the rat.

Beurg M(1), Hafidi A, Skinner L, Cowan G, Hondarrague Y, Mitchell TJ, Dulon D.

Author information:
(1)EA-3665 Université Victor Segalen Bordeaux 2, Laboratoire de Biologie
Cellulaire et Moléculaire de l’Audition, Hôpital Pellegrin, Bat PQR, 33076
Bordeaux, France.

Streptoccocus pneumoniae infection can result in local and systemic diseases such
as otitis media, pneumonia and meningitis. Sensorineural hearing loss associated
with this infection is mediated by the release of an exotoxin, pneumolysin. The
goal of the present study was to characterize the mechanisms of pneumolysin
toxicity in cochlear hair cells in vitro. Pneumolysin induced severe damage in
cochlear hair cells, ranging from stereocilia disorganization to total cell loss.
Surprisingly, pneumolysin-induced cell death preferentially targeted inner hair
cells. Pneumolysin triggered in vitro cell death by an influx of calcium.
Extracellular calcium appeared to enter the cell through a pore formed by the
toxin. Buffering intracellular calcium with BAPTA improved hair cell survival.
The mitochondrial apoptotic pathway involved in pneumolysin-induced cell death
was demonstrated by the use of bongkrekic acid. Binding of pneumolysin to the
hair cell plasma membrane was required to induce cell death. Increasing external
calcium reduced cell toxicity by preventing the binding of pneumolysin to hair
cell membranes. These results showed the significant role of calcium both in
triggering pneumolysin-induced hair cell apoptosis and in preventing the toxin
from binding to its cellular target.

DOI: 10.1113/jphysiol.2005.092478
PMCID: PMC1474774
PMID: 16051626 [Indexed for MEDLINE]

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