Up-regulation of P-glycoprotein expression by osmotic stress in rat sugar cataract.
P-glycoprotein (P-gp), a plasma membrane protein, is thought to function in the export of cytotoxic drugs and to act as a modulator of chloride channels that regulate cell volume in many cell types. P-gp has been shown to play a role in lens volume regulation and initiation of osmotic cataract. We investigated the lenticular expression levels of P-gp in galactose-fed rats, an experimental model of sugar cataract. P-gp was overexpressed in lenses from galactose-fed rats with cortical sugar cataract, and in rat lens epithelial cells cultured in high-glucose medium. However, application of aldose reductase (AR) inhibitor was able to reverse the changes in P-gp levels in the lenses of galactose-fed rats, confirming the role of AR and involvement of the polyol pathway in cataract formation. Our findings suggest that P-gp may be induced by AR over-expression and/or osmotic stress, thus playing a regulatory role in maintaining lenticular osmotic balance in sugar cataract.
Miyazawa
T
T
Department of Ophthalmology, Faculty of Medical Science, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
Kubo
E
E
Takamura
Y
Y
Akagi
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005690:Galactose; D007908:Lens, Crystalline / Q000378:metabolism; D009995:Osmosis; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005136:Eye Proteins; D012333:RNA, Messenger; D000449:Aldehyde Reductase; D005690:Galactose