Calcium ionophore induced proteolysis and cataract: inhibition by cell permeable calpain antagonists.
Two dipeptide aldehyde cell permeable calpain inhibitors, cBz-Val-Phe and calpeptin, have been assessed for their ability to prevent cytoskeletal proteolysis and loss of transparency in whole rat lenses. Calcium overload, induced by ionomycin in artificial aqueous humor with 1mM calcium, resulted in lens opacification and degradation of cytoskeletal proteins including spectrin, filensin, and vimentin. No such changes resulted from incubation in ionomycin in the absence of calcium. In calcium overload lenses both inhibitors gave some protection against cytoskeletal protein degradation and loss of transparency. These experiments indicate that calpain has a role in cortical opacification in high calcium lenses and that cell penetrating calpain inhibitors do indeed enter lens cells and reduce both proteolysis and opacification.
Sanderson
J
J
Cell Biology and Physiology, School of Biological Sciences, University of East Anglia, Norwich, United Kingdom. j.sanderson@uea.ac.uk
Marcantonio
J M
JM
Duncan
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors*; D002386:Cataract / Q000517:prevention & control; D002417:Cattle; D002474:Cell-Free System; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D005136:Eye Proteins / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007908:Lens, Crystalline / Q000378:metabolism*; D008027:Light; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation; D013049:Spectrin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D003598:Cytoskeletal Proteins; D004151:Dipeptides; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D007476:Ionophores; D014746:Vimentin; C079098:filensin; D013049:Spectrin; C071482:calpeptin; D002154:Calpain; D002118:Calcium; C058076:calpain inhibitor III