Involvement of Egr-1 in lens epithelial cell death induced by selenite.
Selenite-overdose cataract in young rats may be caused by an initial insult to the lens epithelial cells. Our previous DNA array analysis revealed a significant increase in the expression of mRNA for early growth response protein-1 (Egr-1) in lens epithelial cells after injection of selenite. This suggested that up-regulation of Egr-1 mRNA may be involved in lens epithelial cell death. The purpose of the present experiment was to further clarify the involvement of Egr-1 in lens epithelial cell death induced by selenite. Rat lens epithelial explants were cultured with sodium selenite. Selenite caused epithelial explants to leak LDH into the medium. During LDH leakage, increased expression of mRNA for Egr-1 was observed by RT-PCR. To further test the involvement of Egr-1 in selenite-induced cell death, mouse lens epithelial cell line (alpha-TN4 cells) was treated with antisense oligonucleotide for Egr-1. Antisense oligonucleotide for Egr-1 significantly diminished expression of Egr-1 protein and leakage of LDH. These results suggested that increased activity of Egr-1 may be a factor in lens epithelial cell death induced by selenite.
Nakajima
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Research Laboratory of Ocular Sciences, Senju Pharmaceutical Co. Ltd, Kobe, Hyogo, Japan.
Belusko
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PB
Walkup
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RD
Azuma
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M
Shearer
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TR
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006836:Hydro-Lyases / Q000378:metabolism; D007903:Lens Capsule, Crystalline / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018038:Sodium Selenite / Q000633:toxicity*; D015854:Up-Regulation
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D006836:Hydro-Lyases; C045581:lactate dehydratase; D018038:Sodium Selenite