Upregulation of HSP by geranylgeranylacetone protects the cochlear lateral wall from endotoxin-induced inflammation.
We investigated whether an acyclic polyisoprenoid antiulcer drug, geranylgeranylacetone (GGA), induces the expression of HSP70 in the rat cochlea. Immunoblotting revealed upregulation of HSP70 in the cochlea at 12 h after transtympanic (local) or oral (systemic) administration of GGA, and this increased at 24 h after administration. Positive immunohistochemical staining of HSP70 was observed in the hair cells, the spiral ganglion, the stria vascularis, the spiral ligament, and the perivascular portion of modiolar vessels. We therefore subsequently studied the effects of GGA as an HSP-inducer on inner ear trauma due to inflammation. Damage to the lateral wall due to inflammation induced by lipopolysaccharide inoculation was protected against by pretreatment with GGA, as assessed physiologically by measurement of cochlear blood flow and morphologically by electron microscopy. The results of the present study suggest that GGA can protect the cochlea against other injuries including those induced by noise, ototoxic drugs, and ischemia by upregulating HSP70.
Sone
Michihiko
M
Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. michsone@med.nagoya-u.ac.jp
Hayashi
Hideo
H
Yamamoto
Hiroshi
H
Hoshino
Tatsuya
T
Mizushima
Toru
T
Nakashima
Tsutomu
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006319:Hearing Loss, Sensorineural / Q000517:prevention & control*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity; D008854:Microscopy, Electron; D015999:Multivariate Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism; D013316:Stria Vascularis / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; C031049:geranylgeranylacetone