Autophagy and pancreatitis

被引:103
作者
Gukovskaya, Anna S. [1 ,2 ]
Gukovsky, Ilya
机构
[1] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA
[2] Univ Calif Los Angeles, Los Angeles, CA USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2012年 / 303卷 / 09期
基金
美国国家卫生研究院;
关键词
macroautophagy; lysosome; cathepsin; lysosome-associated membrane protein; pancreatic acinar cell; trypsin; ACINAR-CELL DEATH; TRYPSINOGEN ACTIVATION; EARLY EVENTS; ORGANELLAR DYSFUNCTION; PROTEIN-DEGRADATION; MAMMALIAN AUTOPHAGY; ZYMOGEN ACTIVATION; IMPAIRED AUTOPHAGY; DUAL ROLE; RAT;
D O I
10.1152/ajpgi.00122.2012
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Acute pancreatitis is an inflammatory disease of the exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. Recent findings from experimental models and genetically altered mice summarized in this review reveal that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis and that one cause of autophagy impairment is defective function of lysosomes. We propose that the lysosomal/autophagic dysfunction is a key initiating event in pancreatitis and a converging point of multiple deranged pathways. There is strong evidence supporting this hypothesis. Investigation of autophagy in pancreatitis has just started, and many questions about the "upstream" mechanisms mediating the lysosomal/autophagic dysfunction and the "downstream" links to pancreatitis pathologies need to be explored. Answers to these questions should provide insight into novel molecular targets and therapeutic strategies for treatment of pancreatitis.
引用
收藏
页码:G993 / G1003
页数:11
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