Calpain裂解Atg5决定中性粒细胞发生自噬还是凋亡，以及C5a在其中的可能作用  

Calpain-mediated Cleavage of Atg5 Determine Autophagy or Apoptosis of PMN, and C5a's Role

作　　者：张保全[1,2] 郭振辉[2] 房巍[2] 吕凤林[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所,创伤烧伤与复合伤国家重点实验室,重庆400042 [2]广州军区总医院MICU科,广州510010

出　　处：《生物化学与生物物理进展》2008年第12期1358-1363,共6页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(39770315,39970330,30371339,30571748);广州市科委攻关引导资助项目(07Z-E0261)~~

摘　　要：通过阐明C5a、calpain和Atg5相互作用,为开展新的研究寻找方向.中性粒细胞凋亡控制炎症反应及其强度,多种疾病和中性粒细胞凋亡失调有关,但其发生机制尚未阐明.C5a为补体片段,有多种功能,如诱导中性粒细胞趋化、呼吸爆发、增强吞噬、颗粒酶释放和延迟凋亡.已知calpain涉及中性粒细胞功能及凋亡调节并对该凋亡发生具有特异性.不同刺激因素可通过不同路径调节不同calpain亚型的活性.已有报道C5a可以通过调节calpain亚型活性而调节中性粒细胞的趋化反应.另外,自噬是真核细胞中广泛存在的生物过程,具有细胞保护作用,Atg5对于自噬体形成必不可少.Calpain可裂解Atg5为24kutAtg5,使其失去形成自噬体的功能并介导凋亡.Atg5参与了自噬和凋亡的转换.Apoptosis of neutrophils controls the duration and the intensity of an inflammatory response and therefore the extent of neutrophil- mediated tissue damage, disturbance of neutrophil apoptosis has been associated with many diseases, underlying mechanism is not elucidated. C5a is a complement fragment that has multifimctional properties, which induces neutrophil chemoattraction, an oxidative burst, enhancement of phagocytosis, release of granule enzymes, and suppress neutrophil apoptosis. Several studies have reported calpain is involved in both neutrophil functions and apoptosis and it might play a more specific role in the regulation of neutrophil apoptosis. Diffenrent isoform of calpains is activted by diffenrent stimuli through different transduction pathway. It was reported previously that calpain is required for neutrophil migration and chemotaxis induced by C5a. In addition, autophagy is a ubiquitous physiological process that occurs in all eukaryotic cells and is considered to be a survival mechanism. Atg5 promotes autophagy and is indispensable to autophagosome formation. Upon calpain activation, Atg5 is cleaved and the resulting 24 ku Atg5 mediates apoptosis while losting the property of autophagy. Therefore, Atg5 represents a molecular switch between autophagy and apoptosis. The interaction among the C5a, calpain and Atg5 was introduced and new direction for further research was provided.

关 键 词：中性粒细胞 凋亡 自噬 Atg5 CALPAIN C5A 

分 类 号：R563[医药卫生—呼吸系统] R310.34[医药卫生—内科学]