Changes in plasma membrane Ca2+ -ATPase expression and ATP content in lenses of hereditary cataract UPL rats.
The UPL rat is a newly developed hereditary cataract model. We previously found that Ca2+ concentrations in UPL rat lenses increase with the development of cataract, and that the administration of disulfiram and aminoguanidine ameliorates the increase in Ca2+ and the development of cataract in UPL rats. In this study, we determined the expression and activity of plasma membrane Ca2+-ATPase (PMCA) in lenses of normal and UPL rats. We also determined the ATP content in UPL rat lenses and the effects of disulfiram and aminoguanidine administration. Expression of PMCA mRNA in UPL rat lenses, determined by a reverse transcription-PCR method, increased during the development of cataract. Ca2+-ATPase activity in UPL rat lenses also increased with the progression of lens opacification. On the other hand, ATP decreased markedly in UPL rat lenses, and the administration of disulfiram and aminoguanidine attenuate the ATP decrease. These results suggest that an ATP decrease cause cataract development and an increased Ca2+ may upregulate PMCA expression in UPL rat lenses. Disulfiram and aminoguanidine attenuate the decrease in ATP, resulting in a delay in cataract development.
Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Kamishin'ei-cho, Niigata 950-2081, Japan. nabe@niigata-pharm.ac.jp
Tomohiro
T
Nabekura
Masayuki
M
Tomohiro
Yoshimasa
Y
Ito
Shuji
S
Kitagawa
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002386:Cataract / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology*; D004195:Disease Models, Animal; D004221:Disulfiram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; C004479:pimagedine; D004221:Disulfiram