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Rhodopsin T17M Mutant Inhibits Complement C3 Secretion in Retinal Pigment Epithelium via ROS Induced Downregulation of TWIST1
Author(s) -
Xiong Siqi,
Yu Yixin,
Zhou Xiaoyun,
Xia Xiaobo,
Jiang Haibo
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26177
Subject(s) - rhodopsin , microbiology and biotechnology , retinal pigment epithelium , secretion , endoplasmic reticulum , retinitis pigmentosa , biology , mutant , transcription factor , western blot , unfolded protein response , retinal , biochemistry , gene
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.