Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.54 (calpain 3)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Observations described here provide the first demonstration that calpain (Ca2+-dependent cysteine protease) can degrade proteins of skeletal muscle plasma membranes. Frog muscle plasma membrane vesicles were incubated with calpain preparations and alterations of protein composition were revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Calpain II (activated by millimolar concentrations of Ca2+) was isolated from frog skeletal muscle, but the activity of calpain I (activated by micromolar concentrations of Ca2+) was lost during attempts at fractionation. Calpain I obtained from skeletal muscle and erythrocytes of rats was tested instead, and exerted effects similar to those of frog muscle calpain on the membrane proteins. All of the calpain preparations caused striking losses of a major membrane protein of molecular mass of approximately 97 kDa, designated band c, and diminution of a thinner band of approximately 200 kDa. There were concomitant increases in 83- and 77-kDa polypeptides. These effects were absolutely dependent on the presence of free Ca2+, and were completely blocked by calpastatin, a specific inhibitor of calpain action. Frog muscle calpain differed only in being relatively more active at 0 degree C than were the calpains from rat tissues. Experimental observations suggest that calpain acts at the cytoplasmic surface of the plasma membrane.
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PMID:Degradation of skeletal muscle plasma membrane proteins by calpain. 255 77

S-nitrosylation by sodium nitroprusside, a nitric oxide-generating agent, inactivates, almost completely at neutral pH, the proteolytic activity of the high Ca2+ requiring calpain form (m-calpain) from skeletal muscle. This inhibition is reversed by treating the inactivated proteinase with dithiothreitol. When exposed to sodium nitroprusside, the single m-calpain-like isoform from human neutrophils is inactivated too. On the contrary, the activities of muscle mu-calpain isoform and the human erythrocyte single mu-calpain-like isoform are poorly affected by nitric oxide treatment at neutral pH; however, inactivation is progressively enhanced if the pH of incubation mixtures is shifted to acidic values, a condition which conversely reduces NO-mediated inactivation of m-calpain. On the basis of these results, it is conceivable to postulate that nitric oxide may exert a regulatory role of muscle calpain activity by modulation of either one or the other proteinase isoform, also in concomitance with fluctuations of hydrogen ions in contracting cells occurring in physiological or pathological conditions. The regulatory role of nitric oxide is also supported by the observation that S-nitrosylation induces inactivation of calpain also in intact human neutrophils. Furthermore, the reversibility of the inactivation of calpain by nitric oxide may be exploited to study the relationship between the molecular structure and the catalytic and regulatory mechanisms of this neutral proteinase.
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PMID:Reversible inactivation of calpain isoforms by nitric oxide. 786 86