Affordable Access

deepdyve-link
Publisher Website

Rhodopsin T17M Mutant Inhibits Complement C3 Secretion in Retinal Pigment Epithelium via ROS Induced Downregulation of TWIST1.

Authors
  • Xiong, Siqi1
  • Yu, Yixin1
  • Zhou, Xiaoyun1
  • Xia, Xiaobo1
  • Jiang, Haibo1
  • 1 Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, 410078, China. , (China)
Type
Published Article
Journal
Journal of Cellular Biochemistry
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2017
Volume
118
Issue
12
Pages
4914–4920
Identifiers
DOI: 10.1002/jcb.26177
PMID: 28569420
Source
Medline
Keywords
License
Unknown

Abstract

Rhodopsin mutations cause autosomal dominant form of retinitis pigmentosa (RP). T17M rhodopsin predisposes cells to endoplasmic reticulum stress induced apoptosis. However, the pathogenic role of T17M rhodopsin in RP is not completely understood. Complement C3 has a protective role in RP pathogenesis. This study aimed to investigate whether T17M rhodopsin regulates C3 secretion in retinal pigment epithelium. The human retinal pigment epithelial cell line (ARPE-19) was engineered to overexpress wide-type (WT) and T17M rhodopsin. Gene expression was detected by RT-PCR and Western blot analysis. C3 secretion was detected by ELISA. The overexpression of T17M rhodopsin significantly induced ROS and reduced C3 secretion and transcription in ARPE-19 cells, but ROS scavengers could partially rescue reduced C3 secretion and transcription. Mechanistically, we found that ROS suppressed transcription factor TWIST1 which is responsible for activated transcription of C3. In conclusion, our data provide the first evidence that T17M rhodopsin mutant disrupts C3 secretion via the induction of ROS and the suppression of TWIST1. These findings reveal novel insight into the pathogenic role of mutant rhodopsin in RP. J. Cell. Biochem. 118: 4914-4920, 2017. © 2017 Wiley Periodicals, Inc.

Report this publication

Statistics

Seen <100 times