Amelioration of cataracts and proteolysis in cultured lenses by cysteine protease inhibitor E64

Thomas (Tom) Shearer, M. Azuma, Larry David, T. Murachi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Cataracts were produced in cultured rat lenses by either 10 μM calcium, ionophore A23187, 25 μM sodium selenite, or 30 mM xylose. E64, an inhibitor of cysteine proteases, such as calpain (EC.3.4.22.17), reduced severity of cataract and proteolysis of crystallins when included at a 500 μM concentration in the culture medium along with cataractogenic agents. Calpain II enzyme activity and the amount of calpain antigen were decreased in the cytosol of cataractous lens. However, E64 caused an increase in the amount of an 80-kD calpain subunit associated with the ethyleneglycol-bis-(β-aminoethylether) tetraacetic acid/ethylenediaminetetraacetic acid-washed insoluble proteins when lenses were incubated with cataractous agents. These data indicate that E64 was at least partially effective in inhibiting lens calpain, and that activation of lens calpain may involve binding to the insoluble fraction. These results provide strong evidence for the activation of calpain in rodent cataracts and suggest testing inhibitors of calpain as anticataract drugs.

Original languageEnglish (US)
Pages (from-to)533-540
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume32
Issue number3
StatePublished - 1991

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Cysteine Proteinase Inhibitors
Calpain
Cataract
Lenses
Proteolysis
Crystallins
Sodium Selenite
Calcium Ionophores
Xylose
Calcimycin
Edetic Acid
Cytosol
Culture Media
Rodentia
Antigens
Acids
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Amelioration of cataracts and proteolysis in cultured lenses by cysteine protease inhibitor E64. / Shearer, Thomas (Tom); Azuma, M.; David, Larry; Murachi, T.

In: Investigative Ophthalmology and Visual Science, Vol. 32, No. 3, 1991, p. 533-540.

Research output: Contribution to journalArticle

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