Inhibition of calpain but not caspase activity by spectrin fragments

Cellular & Molecular Biology Letters

Qufei Li¹  Leslie W.-M. Fung¹  Chloe Antoniou¹  Garrett Cobb¹  Pooja Gala¹  Lidia A. Nazarova¹  Priyanka Rajaram¹  Ramunas Rolius¹  Stephen H. Kim¹ 

[1] Department of Chemistry, University of Illinois at Chicago, Chicago, USA$$

关键词: Spectrin;    Calpain;    Caspase;    Calpain inhibition;    Cysteine protease;   

DOI  :  10.2478/s11658-010-0015-3

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

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) α- and β-spectrin and erythroid β-spectrin. The cleavage of erythroid α-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 α-spectrin, and C-terminal region of β-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.

【 授权许可】

Unknown