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Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice
Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo 002-8072, Japan
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube 755-8505, Japan
* Author to whom correspondence should be addressed.
Received: 7 November 2012; in revised form: 9 January 2013 / Accepted: 18 January 2013 / Published: 22 January 2013
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&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.
Keywords: GGA; geranylgeranylacetone; HSP; HSP70; UVB; keratitis; cornea; apoptosis
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Lennikov, A.; Kitaichi, N.; Kase, S.; Noda, K.; Horie, Y.; Nakai, A.; Ohno, S.; Ishida, S. Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice. Int. J. Mol. Sci. 2013, 14, 2175-2189.
Lennikov A, Kitaichi N, Kase S, Noda K, Horie Y, Nakai A, Ohno S, Ishida S. Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice. International Journal of Molecular Sciences. 2013; 14(1):2175-2189.
Lennikov, Anton; Kitaichi, Nobuyoshi; Kase, Satoru; Noda, Kousuke; Horie, Yukihiro; Nakai, Akira; Ohno, Shigeaki; Ishida, Susumu. 2013. "Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice." Int. J. Mol. Sci. 14, no. 1: 2175-2189.