Modelling cortical cataractogenesis. XXIX. Calpain proteolysis of lens fodrin in cataract.
The relation between cataract and calpain proteolysis of lens fodrin was studied in two systems: elevated glucose (55.6 mM, diabetic model), and cytochalasin D (CD, 10(-2) mM, actin depolymerization-induced opacity model). Glucose treatment (48 h) caused a visible opaque layer and enzyme leakage, with a concomitant accumulation of ([Ca2+]i) around the lens equatorial cortex. CD caused both earlier and greater opacity and enzyme leakage than glucose. Lens fodrin digestion occurred in parallel with the timing and extent of calcium elevation. A calpain inhibitor peptide (CIP, 10(-2) mM) reduced the proteolysis of fodrin, opacity, and enzyme leakage in glucose-treated lenses but only partially retarded them in CD-treated lenses. These results suggest a mechanism in which calpain proteolysis of fodrin is a critical event in lens damage during opacification of cortical cataract.
Kilic
F
F
Department of Biochemistry, Faculty of Medicine, University of Western Ontario, London, Canada.
Trevithick
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D046508:Culture Techniques; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005947:Glucose / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007904:Lens Cortex, Crystalline / Q000378:metabolism / Q000473:pathology; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009930:Organic Chemicals; D011726:Pyridinium Compounds; D051381:Rats; D013049:Spectrin
D002118:Calcium; D002154:Calpain; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D015638:Cytochalasin D; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005947:Glucose; D006023:Glycoproteins; D007770:L-Lactate Dehydrogenase; D008840:Microfilament Proteins; D009930:Organic Chemicals; D011726:Pyridinium Compounds; D013049:Spectrin; C039304:calpain inhibitors; C071336:calcium green; C054158:RH 414; C018506:diacetylfluorescein