title: Induction of heat shock protein 70 ameliorates  ultraviolet-induced photokeratitis in mice.
abstract: Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP)70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice.  C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse) and  UVB-exposed (400 mJ/cm2), GGA-untreated UVB-exposed (400 mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naive controls. Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H&amp;E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). HSP70, reactive oxygen species (ROS) production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and protein kinase B (Akt) expression were also evaluated. Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0.01). Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0.01). Corneal HSP70 levels were significantly elevated in corneas of mice treated with  GGA (p < 0.05). ROS signal was not affected by GGA. NF-κB activation was reduced but phospho-(Ser/Ther) Akt substrate expression was increased in corneas after irradiation when treated with GGA. GGA-treatment induced HSP70 expression and ameliorated  UV-induced corneal damage through the reduced NF-κB activation and possibly increased Akt phosphorilation.
authors: Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. nobukita@med.hokudai.ac.jp.
authors: Anton
authors: A
authors: Lennikov
authors: Nobuyoshi
authors: N
authors: Kitaichi
authors: Satoru
authors: S
authors: Kase
authors: Kousuke
authors: K
authors: Noda
authors: Yukihiro
authors: Y
authors: Horie
authors: Akira
authors: A
authors: Nakai
authors: Shigeaki
authors: S
authors: Ohno
authors: Susumu
authors: S
authors: Ishida
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007634:Keratitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; C031049:geranylgeranylacetone