TY - JOUR
T1 - SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain
T2 - Amelioration of cataract in cultured rat lenses
AU - Fukiage, Chiho
AU - Azuma, Mitsuyoshi
AU - Nakamura, Yoshikuni
AU - Tamada, Yoshiyuki
AU - Nakamura, Masayuki
AU - Shearer, Thomas R.
N1 - Funding Information:
The authors gratefully thank Dr. Kevin Wang (Parke-Davis) and Mr. Jun Inoue (Senju) for helpful discussions. This investigation was supported in part by NIH grant EY05786 to T.R.S.
PY - 1997/10/24
Y1 - 1997/10/24
N2 - 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.
AB - 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.
KW - Calcium ionophore A23187
KW - Calpain
KW - Cataract
KW - Proteolysis
KW - SJA6017
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U2 - 10.1016/S0925-4439(97)00043-4
DO - 10.1016/S0925-4439(97)00043-4
M3 - Article
C2 - 9375805
AN - SCOPUS:0030707575
SN - 0925-4439
VL - 1361
SP - 304
EP - 312
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 3
ER -