Calpain is activated in degenerating photoreceptors in the rd1 mouse

• Published in: Journal of neurochemistry Vol. 96; no. 3; pp. 802 - 814
• Main Authors: Paquet‐Durand, Francois, Azadi, Seifollah, Hauck, Stefanie M., Ueffing, Marius, Veen, Theo, Ekström, Per
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2006; Blackwell; Blackwell Publishing Ltd
• Subjects: Age Factors; Animals; Animals, Newborn; Basic Medicine; Biological and medical sciences; Blotting, Western - methods; calcium; Calcium-Binding Proteins - metabolism; calpain; Calpain - metabolism; calpastatin; Cyclic AMP Response Element-Binding Protein - metabolism; Enzyme Activation - physiology; Enzymes; Eye and associated structures. Visual pathways and centers. Vision; Fluorescent Antibody Technique - methods; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Glycoproteins - pharmacology; In Situ Nick-End Labeling - methods; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C3H; microarray; Microarray Analysis - methods; Neurons; Neurosciences; Neurovetenskaper; Ophthalmology; Photoreceptor Cells, Vertebrate - enzymology; Retina; Retinal Degeneration - enzymology; Retinal Degeneration - pathology; retinitis pigmentosa; Retinopathies; Rodents; Transcription, Genetic - physiology; Vertebrates: nervous system and sense organs; Retinopathy; Calcium; Retinitis pigmentosa; Cysteine endopeptidases; Photoreceptor; Retina; calpastatin; Activation; Macular degeneration; Visual system; Binding protein; Transcription factor CREB; Enzyme; Rodentia; Cyclic AMP; Calpain; Response element; Genetic disease; Peptidases; Eye disease; Vertebrata; microarray; Mammalia; Mouse; Cell death; Hydrolases; Technique
• DOI: 10.1111/j.1471-4159.2005.03628.x
• ISSN: 0022-3042; 1471-4159

The retinal degeneration (rd)1 mouse displays an inherited retinal degeneration and therefore allows studies of the molecular mechanisms behind the blinding disease retinitis pigmentosa. Activation of the calcium‐dependent protease calpain has been suggested to play an important role in cell death in various tissues, but little is known about the expression and activity of calpain during inherited retinal degeneration. Using microarray techniques, transcript levels of cyclic AMP response element‐binding protein (CREB)‐1, calpastatin and of various calpain genes were analysed in the rd1 mouse compared with its wild‐type control. Expression of distinct calpain isoforms and calpastatin was investigated using immunofluorescence and immunoblotting. Gene transcription and protein expression levels were compared with calpain activity using an enzymatic assay that allowed monitoring of calpain activity at the cellular level. We found that CREB‐1 and calpastatin expression was reduced in rd1 retinas, whereas calpain activity was substantially increased in rd1 photoreceptors. Calpain activity peaked at postnatal day 13, together with rd1 photoreceptor cell death. Calpain‐specific inhibitors decreased calpain activity in situ. These results indicate that activation of calpains correlates with rd1 photoreceptor cell death, which raises the possibility of using calpain inhibitors to prevent or delay photoreceptor degeneration.