title: Differential expression of heat shock protein mRNAs under in vivo glutathione depletion in the mouse retina.
abstract: Heat shock proteins (HSPs) are highly conserved proteins playing a protective role under deleterious conditions caused by a wide variety of pathophysiological, including environmental stresses. Glutathione (GSH) is known to play a critical role in the cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH depletion induced cell death in the retina, but the mechanism(s) of cellular protection were not clear. Unregulated oxidative stress was induced by depletion of intracellular GSH by systematic administration of buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase. After 0, 1, 4 and 7 days of BSO administration, we examined expression of both large and small HSP mRNAs (hsp90alpha, hsp90beta, hsp70, hsp60 and hsp25) in oxidative-stressed mouse retina. Of large HSPs, only hsp70 expression was significantly decreased from 1 day after BSO injection, whereas expression of other large hsps was not changed on day 1. Expression of hsp60 decreased on 4 days, whereas expression of hsp90 decreased on 7 days after BSO administration. Different from large HSPs, a small HSP, hsp25 increased its expression to a great extent from 1 day after BSO administration. Taken together, our results show that unregulated oxidative stress could induce differential expression of HSPs, which, in turn, may play distinct roles in the cellular defense. Targeting HSPs, therefore, may provide novel tools for treatment of retinal degenerative diseases such as glaucoma, retinopathy or age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Joo Wan
authors.initials: JW
authors.lastname: Park
authors.forename: Cheil
authors.initials: C
authors.lastname: Moon
authors.forename: Sunmi
authors.initials: S
authors.lastname: Yun
authors.forename: So Yeun
authors.initials: SY
authors.lastname: Kim
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.forename: Myung-Hoon
authors.initials: MH
authors.lastname: Chun
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Moon
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005978:Glutathione / Q000172:deficiency*; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D019328:Buthionine Sulfoximine; D005978:Glutathione