Inhibition of proteolysis by a cyclooxygenase inhibitor, indomethacin

The effect of indomethacin, a non-steroidal anti-inflammatory drug upon purified calpain has been studied. Also, its effects upon Ca2+-mediated degradation of cytoskeletal proteins (neurofilament) in spinal cord homogenate has been investigated. A dose-dependent inhibition of purified calpain activi...

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Bibliographic Details
Published in:Neurochemical research 2000-11, Vol.25 (11), p.1509-1515
Main Authors: BANIK, Naren L, MATZELLE, Denise, TERRY, Elaine, GANTT-WILFORD, Gloria, HOGAN, Edward L
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Calpain - metabolism
Caseins - metabolism
Cyclooxygenase Inhibitors - pharmacology
Hydrolysis
Indomethacin - pharmacology
Medical sciences
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Spinal Cord - drug effects
Spinal Cord - enzymology
Spinal Cord - metabolism
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Summary:The effect of indomethacin, a non-steroidal anti-inflammatory drug upon purified calpain has been studied. Also, its effects upon Ca2+-mediated degradation of cytoskeletal proteins (neurofilament) in spinal cord homogenate has been investigated. A dose-dependent inhibition of purified calpain activity was observed. A 50% inhibition of 14C-caseinolytic activity was obtained with less than 1.1 mM of indomethacin while the activity was completely inhibited at 3.3 mM concentration. The inhibitory effect of ketorlac, another non-steroidal anti-inflammatory drug, upon calpain was weaker than that of indomethacin. The degradation of myelin basic protein (MBP) by cathepsin B, a lysosomal cysteine protease, was significantly inhibited by indomethacin. It also inhibited the Ca2+-mediated degradation of neurofilament protein (NFP) in spinal cord homogenate. The extent of NFP degradation was analyzed by SDS-PAGE and the inhibition shown by indomethacin was weaker than that observed with leupeptin and the calpain inhibitor E64-d. The inhibitory effect of indomethacin on the activity of multicatalytic proteinase complex was negligible. These results suggest that indomethacin, a non-steroidal anti-inflammatory drug and cyclooxygenase inhibitor also inhibits proteinases, including cathepsin B and calpain.
ISSN:0364-3190
1573-6903
DOI:10.1023/A:1007684311023