calpastatin and Cataract

Topics: Alzheimer Disease; Amino Acid Sequence; Animals; Apoptosis; Binding Sites; Calcium-Binding Proteins; Calpain; Cataract; Cell Cycle; Cysteine Proteinase Inhibitors; Enzyme Activation; Humans; Long-Term Potentiation; Muscular Dystrophies; Parkinson Disease; Substrate Specificity

Selenite overdose cataract, an experimental model of nuclear cataract produced in young rats is reviewed. Topics include procedures for cataract production and assessment, metabolic and molecular changes in the epithelium of the lens, calcium accumulation, activation of calcium-activated protease system, mechanisms for crystallin precipitation, anti-cataract drug testing and relevance to human cataract.

Topics: Animals; Calcium; Calcium-Binding Proteins; Calpain; Cataract; Chemical Precipitation; Crystallins; Cysteine Proteinase Inhibitors; Cytoskeletal Proteins; Disease Models, Animal; Drug Evaluation, Preclinical; Epithelium; Forecasting; Lens, Crystalline; Rats; RNA, Messenger; Sodium Selenite

The human genome contains 14 genes for 80 kDa catalytic subunit of the calcium-activated protease calpain (EC 34.22.17), yet no calpain-like cleavage sites have been detected on human lens crystallins in vivo. The purpose of the present study was to provide a comprehensive study of calpain activation in human and macaque lenses developing experimental cataract due to lens culture in ionophore A23187. Zymography was used to measure calpain activity; SDS-PAGE and immunoblotting were used to detect hydrolysis of potential lens protein substrates. Quantitative PCR was used to measure transcripts for calpains and the endogenous inhibitor calpastatin. We found that the lack of appreciable calpain-induced proteolysis in primate lenses is most likely due to relatively low levels of endogenous calpain activity compared to the high levels of endogenous calpain inhibitor, calpastatin.

Topics: Aged; Aged, 80 and over; Animals; Apoptosis; Calcimycin; Calcium; Calcium-Binding Proteins; Calpain; Caseins; Cataract; Eye Proteins; Humans; Immunoblotting; In Situ Nick-End Labeling; Ionophores; Lens, Crystalline; Macaca mulatta; Models, Animal; Reverse Transcriptase Polymerase Chain Reaction; Staining and Labeling

Calpains are Ca-activated neutral proteases present in all cells together with an endogenous inhibitor, calpastatin. Proposed substrates are; cytoskeletal proteins like microtubules and actin, protein kinases such as PKC and membrane-bound enzymes like Ca-ATPase and the Ca-channel. In lenses from different species calpains have been detected in decreasing amounts from the epithelium to the cortex to the nucleus. Several substrates for calpain in the lens have been demonstrated: crystallins, vimentin, actin, beaded filaments and MP26 among others. Both studies on animal models and capsulorhexis indicate that calpains are mainly involved in cortical cataract.

Topics: Calcium; Calcium-Binding Proteins; Calpain; Cataract; Epithelium; Humans; Lens, Crystalline; Substrate Specificity