SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain: amelioration of cataract in cultured rat lenses.
The purposes of this experiment were to: (1), characterize the peptide aldehyde SJA6017, N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal, a newly synthesized inhibitor of calpain, and (2) test the effect of SJA6017 in preventing calcium ionophore-induced cataract in cultured rat lenses. In vitro, SJA6017 strongly inhibited purified m-calpain from porcine kidney. Casein zymography confirmed that SJA6017 reversibly bound to the active site of m-calpain. SJA6017 was also confirmed to be a cell-permeable inhibitor in Molt-4 cells. In cultured lenses, SJA6017 reduced nuclear opacity and proteolysis of crystallins and alpha-spectrin caused by calcium ionophore A23187. These results suggested that SJA6017 is a reversible and cell-permeable calpain inhibitor which may possess great efficacy against calcium-induced models of cataract.
Fukiage
C
C
Department of Oral Molecular Biology and Ophthalmology, Oregon Health Sciences University, Portland 97201, USA.
Azuma
M
M
Nakamura
Y
Y
Tamada
Y
Y
Nakamura
M
M
Shearer
T R
TR
D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D002386:Cataract / Q000188:drug therapy* / Q000201:enzymology; D046508:Culture Techniques; D004151:Dipeptides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006868:Hydrolysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004151:Dipeptides; D004791:Enzyme Inhibitors; C109145:N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal; D002154:Calpain