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

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Title: Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice
Authors: Lennikov, Anton Browse this author
Kitaichi, Nobuyoshi Browse this author →KAKEN DB
Kase, Satoru Browse this author →KAKEN DB
Noda, Kousuke Browse this author →KAKEN DB
Horie, Yukihiro Browse this author
Nakai, Akira Browse this author
Ohno, Shigeaki Browse this author →KAKEN DB
Ishida, Susumu Browse this author →KAKEN DB
Keywords: GGA
geranylgeranylacetone
HSP
HSP70
UVB
keratitis
cornea
apoptosis
Issue Date: Jan-2013
Publisher: MDPI
Journal Title: International Journal of Molecular Sciences
Volume: 14
Issue: 1
Start Page: 2175
End Page: 2189
Publisher DOI: 10.3390/ijms14012175
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.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/52140
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 北市 伸義

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