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, SJ...

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Bibliographic Details
Published in:Biochimica et biophysica acta 1997-10, Vol.1361 (3), p.304-312
Main Authors: Fukiage, Chiho, Azuma, Mitsuyoshi, Nakamura, Yoshikuni, Tamada, Yoshiyuki, Nakamura, Masayuki, Shearer, Thomas R
Format: Article
Language:English
Subjects:
Animals
Calcium ionophore A23187
Calpain
Calpain - antagonists & inhibitors
Cataract
Cataract - drug therapy
Cataract - enzymology
Culture Techniques
Dipeptides - pharmacology
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Hydrolysis
Proteolysis
Rats
Rats, Sprague-Dawley
SJA6017
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Summary: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 α-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.
ISSN:0925-4439
0006-3002
1879-260X
DOI:10.1016/S0925-4439(97)00043-4