title: Chemical chaperone 4-phenylbutyrate prevents endoplasmic reticulum stress induced by T17M rhodopsin.
abstract: BACKGROUND
  Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M.
  
  
  RESULTS
  ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chase analysis. The activity of ubiquitin-proteasome system was evaluated by GFPU reporter. We found that T17M rhodopsin was misfolded, ubiqutinated and eliminated by ER-associated degradation pathway (ERAD) in ARPE-19 cells. Accumulated T17M rhodopsin induced unfolded protein response, but had no effect on the activity of ubiquitin proteasome system. Moreover, chemical chaperone 4-phenylbutyrate facilitated the turnover of T17M rhodopsin and prevented apoptosis and ER stress induced by T17M rhodopsin.
  
  
  CONCLUSIONS
  Chemical chaperone could attenuate UPR signaling and ER stress induced by T17M rhodopsin and has potential therapeutic significance for retinitis pigmentosa.
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410078 P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410078 P.R. China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410078 P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xia
keywords: ERAD; Misfolded; Retinitis pigmentosa; Rhodopsin; UPR