RRC ID 2770
Author Ikesugi K, Yamamoto R, Mulhern ML, Shinohara T.
Title Role of the unfolded protein response (UPR) in cataract formation.
Journal Exp. Eye Res.
Abstract Cataract is a multifactorial disease, and a large variety of stressors induce cataracts. Many cataractogenic stressors and endoplasmic reticulum (ER) stressors induce the unfolded protein response (UPR) in various cell types. The UPR is known to produce reactive oxygen species (ROS) prior to the inducement of apoptosis. We investigated whether ER stressors induce the UPR in lens epithelial cells (LECs) or whole rat lenses. Our results showed that higher levels of ER stressors activated Bip/GRP78, ATF4, and caspase-12. In addition, ROS were produced, free glutathione was decreased, and apoptosis was induced. LECs in the mitotic zone were the most susceptible to the UPR while the central LECs were the most resistant. The UPR induced the production of ROS in the ER and probably in the mitochondria. The detectable ROS production in cultured lenses is limited to the epithelial cells. These findings indicate that ER stressors induce the UPR in LECs with and without the induction of apoptosis, and we conclude that the UPR is probably one of the initiating factors of many types of cataracts.
Volume 83(3)
Pages 508-16
Published 2006-9
DOI 10.1016/j.exer.2006.01.033
PII S0014-4835(06)00168-0
PMID 16643900
MeSH Animals Calcimycin / pharmacology Cataract / metabolism* Cell Line, Transformed Epithelial Cells / drug effects Epithelial Cells / metabolism* Glucose / metabolism Glutathione / metabolism Glycosylation / drug effects Homocysteine / pharmacology Humans Ionophores / pharmacology Lens, Crystalline / drug effects Lens, Crystalline / metabolism* Molecular Chaperones Protein Folding* Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Tissue Culture Techniques Tunicamycin / pharmacology
IF 3.152
Times Cited 46