SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain: amelioration of cataract in cultured rat lenses.

Abstract

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.

• Authors: C Fukiage, M Azuma, Y Nakamura, Y Tamada, M Nakamura, T R Shearer
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1361 Issue 3 Pg. 304-12 (Oct 24 1997) ISSN: 0006-3002 [Print] Netherlands
• PMID: 9375805 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dipeptides
• Enzyme Inhibitors
• N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal
• Calpain

Topics

• Animals
• Calpain (antagonists & inhibitors)
• Cataract (drug therapy, enzymology)
• Culture Techniques
• Dipeptides (pharmacology)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Hydrolysis
• Rats
• Rats, Sprague-Dawley