Differences in Unfolded Protein Response Pathway Activation in the Lenses of Three Types of Cataracts

• Published in: PloS one Vol. 10; no. 6; p. e0130705
• Main Authors: Yang, Jing, Zhou, Sheng, Gu, Jianjun, Wang, Yujuan, Guo, Minfei, Liu, Yizhi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.06.2015; Public Library of Science (PLoS)
• Subjects: Activating Transcription Factor 4 - genetics; Activating Transcription Factor 4 - metabolism; Activating Transcription Factor 6 - genetics; Activating Transcription Factor 6 - metabolism; Activation; Age; Cataract - metabolism; Cataract - pathology; Cataracts; Cyprinus carpio; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endoplasmic reticulum; Endoribonucleases - metabolism; Eukaryotic Initiation Factor-2 - metabolism; Eye lens; Eye surgery; Gene expression; Genetic disorders; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Kinases; Laboratories; Lens, Crystalline - metabolism; Lenses; Membranes; Myopia; Ophthalmology; Patients; Protein folding; Protein-Serine-Threonine Kinases - metabolism; Proteins; Real-Time Polymerase Chain Reaction; Regulation; Regulatory Factor X Transcription Factors; RNA Splicing; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stress response; Surgery; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Unfolded Protein Response - physiology; Up-Regulation; Western blotting; X-Box Binding Protein 1; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130705

To investigate the activation of three unfolded protein response (UPR) pathways in the lenses of age-related, high myopia-related and congenital cataracts. Lens specimens were collected from patients during small incision cataract surgery. Lenses from young cadaver eyes were collected as normal controls. Real-time PCR and Western blotting were performed to detect the expression of GRP78, p-eIF2α, spliced XBP1, ATF6, ATF4 and p-IRE1α in the lenses of normal human subjects and patients with age-related, myopia-related or congenital cataracts. In the lenses of the age-related and high myopia-related cataract groups, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased. Additionally, in the congenital cataract group, the protein levels of p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78 and ATF4 were greatly increased. However, the protein and gene expression levels of ATF6 were not up-regulated in the congenital cataract group compared with the normal control group. The UPR is activated via different pathways in the lenses of age-related, high myopia-related and congenital cataracts. UPR activation via distinct pathways might play important roles in cataractogenesis mechanisms in different types of cataracts.