Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice

• Lennikov, Anton

• Kitaichi, Nobuyoshi

• Kase, Satoru

• Noda, Kousuke

• Horie, Yukihiro

• Nakai, Akira

• Ohno, Shigeaki

• Ishida, Susumu

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.

Journal

• International Journal of Molecular Sciences

  International Journal of Molecular Sciences 14 (1), 2175-2189, 2013-01

  MDPI

Keywords

• GGA
• geranylgeranylacetone
• HSP
• HSP70
• UVB
• keratitis
• cornea
• apoptosis

Details

• CRID: 1050564288966692992
• NII Article ID: 120005228266
• HANDLE: 2115/52140
• ISSN: 14220067
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles