Naphthoquinone-Induced cataract in mice: possible involvement of Ca2+ release and calpain activation.
N-acetyl-p-benzoquinone imine (NAPQI), a semiquinone metabolite of acetaminophen, produces cataract in mice. Naphthalene is biotransformed to the cataractogenic metabolite 1,2-naphthoquinone (NQ). Intracameral injection of NAPQI elicits a rapid increase in free intracellular Ca2+ in the lens epithelium and calpain activation before lens opacification begins. In order to test whether the cellular response is a common feature of quinone-induced cataracts, we injected in this work 1,2-naphthoquinone (NA) in the anterior chamber of mouse eye and followed cellular responses in the lens prior to opacity development. A marked rise in free intracellular Ca2+ in the lens epithelium and concurrent activation of calpain were observed within 1 hr after NQ injection preceding lens opacity development. These results support the suggestion that Ca2+ release and calpain activation are involved in the mechanism of quinone-induced cataractogenesis.
Qian
W
W
Department of Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Shichi
H
H
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009285:Naphthoquinones / Q000633:toxicity*; D009842:Oligopeptides / Q000494:pharmacology
D006023:Glycoproteins; D009285:Naphthoquinones; D009842:Oligopeptides; C039304:calpain inhibitors; C069861:calpain inhibitor 2; C040756:1,2-naphthoquinone; D002154:Calpain; D002118:Calcium