Inhibition of calpain but not caspase activity by spectrin fragments.
Calpains and caspases are ubiquitous cysteine proteases that are associated with a variety of cellular pathways. Calpains are involved in processes such as long term potentiation, cell motility and apoptosis, and have been shown to cleave non-erythroid (brain) alpha- and beta-spectrin and erythroid beta-spectrin. The cleavage of erythroid alpha-spectrin by calpain has not been reported. Caspases play an important role in the initiation and execution of apoptosis, and have been shown to cleave non-erythroid but not erythroid spectrin. We have studied the effect of spectrin fragments on calpain and caspase activities. The erythroid and non-erythroid spectrin fragments used were from the N-terminal region of alpha-spectrin, and C-terminal region of beta-spectrin, both consisting of regions involved in spectrin tetramer formation. We observed that the all spectrin fragments exhibited a concentration-dependent inhibitory effect on calpain, but not caspase activity. It is clear that additional studies are warranted to determine the physiological significance of calpain inhibition by spectrin fragments. Our findings suggest that calpain activity is modulated by the presence of spectrin partial domains at the tetramerization site. It is not clear whether the inhibitory effect is substrate specific or is a general effect. Further studies of this inhibitory effect may lead to the identification and development of new therapeutic agents specifically for calpains, but not for caspases. Proteins/peptides with a coiled coil helical conformation should be studied for potential inhibitory effects on calpain activity.
Rolius
Ramunas
R
Department of Chemistry, University of Illinois at Chicago, 60607, USA.
Antoniou
Chloe
C
Nazarova
Lidia A
LA
Kim
Stephen H
SH
Cobb
Garrett
G
Gala
Pooja
P
Rajaram
Priyanka
P
Li
Qufei
Q
Fung
Leslie W-M
LW
D017209:Apoptosis; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; D013049:Spectrin; D002154:Calpain; D020169:Caspases
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