title: Effect of Geranylgeranylacetone on Ultraviolet Radiation Type B-Induced Cataract in Heat-Shock Transcription Factor 1 Heterozygous Mouse.
abstract: We investigated whether heat-shock transcription factor 1 (HSF1) was involved in ultraviolet radiation type B (UVR-B)-induced lens opacity (cataract) using HSF1 heterozygous mice. We also examined the effects of geranylgeranylacetone (GGA), an inducer of heat-shock proteins via activation of HSF, on the UVR-B-induced cataract.
  
  
  
  Male HSF1+/-and WT mice were unilaterally exposed to UVR-B (total: 1200mJ) at 16 weeks of age. At 48 h after the last UVR-B irradiation, the lens was isolated and the induction of the cataract was quantified as the cataract area ratio (opacity area/anterior capsule). GGA was orally administered at a dosage of 500 mg/kg once a day for two days before the first UVR-B exposure until the end of the experiment (21days in total).
  
  
  
  The HSF1 expression was more greatly decreased in the lens from HSF1+/-mice than in that from WT mice (p < 0.01). UVR-B exposure could mainly induce cataracts in the anterior capsule in both HSF1+/-and WT mice, while the opacity of the lens was markedly enhanced in HSF1+/-mice compared to that in WT mice(p (0.01). GGA treatment could prevent the induction of lens opacity by UVR-B exposure in both WT and HSF1+/-mice as compared with the non-administration group (p < 0.01). No obvious alteration by the UVR-B radiation was seen in lens protein levels of αA-crystallin, αB-crystallin, or γ-crystallin with or without GGA administration among all groups of mice. In contrast to the crystallins, the lens protein level of HSP25 was decreased by UVR-B exposure in both HSF1+/-and WT mice, and was significantly recovered in WT mice by the GGA treatment (p < 0.01). The induction of HSP25 was suppressed in HSF1+/-mice compared with that in WT mice.
  
  
  
  These data suggest that HSF1 plays an important role in the occurrence of UVR-B-induced cataracts, possibly via regulation of HSPs such as HSP25.
authors.affiliation: a Department of Ophthalmology, School of Medicine , Iwate Medical University , Morioka , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.affiliation: a Department of Ophthalmology, School of Medicine , Iwate Medical University , Morioka , Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Hashizume
authors.affiliation: a Department of Ophthalmology, School of Medicine , Iwate Medical University , Morioka , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okuno
authors.affiliation: a Department of Ophthalmology, School of Medicine , Iwate Medical University , Morioka , Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: b Department of Pharmacotherapeutics , School of Pharmacy, Iwate Medical University , Shiwa-gun , Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Inomata
authors.affiliation: b Department of Pharmacotherapeutics , School of Pharmacy, Iwate Medical University , Shiwa-gun , Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tezuka
authors.affiliation: b Department of Pharmacotherapeutics , School of Pharmacy, Iwate Medical University , Shiwa-gun , Japan.
authors.forename: Atushi
authors.initials: A
authors.lastname: Sanbe
authors.affiliation: a Department of Ophthalmology, School of Medicine , Iwate Medical University , Morioka , Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Kurosaka
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002386:Cataract / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004252:DNA Mutational Analysis; D004224:Diterpenes / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D006579:Heterozygote; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012313:RNA / Q000235:genetics*; D011833:Radiation Injuries, Experimental; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D004224:Diterpenes; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D012313:RNA; C031049:geranylgeranylacetone
keywords: Cataract; geranylgeranylacetone; heat-shock protein transcription factor 1; heat-shock proteins; ultraviolet radiation type B