The fusion of autophagosome with lysosome is impaired in L-arginine-induced acute pancreatitis

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11164-70. eCollection 2015.

Abstract

Background & aims: Acute pancreatitis is an inflammatory pancreatic disease that carries considerable morbidity and mortality. The pathogenesis of this disease remains poorly understood. We investigated the incidence of autophagy in mice following induction of acute pancreatitis.

Methods: Mice were received intraperitoneal injections of L-arginine (200 mg × 2/100 g BW), while controls were administered with saline. Pancreatic tissues were assessed by histology, electron microscopy and western blotting.

Results: Injection of L-arginine resulted in the accumulation of autophagosomes and a relative paucity of autolysosomes. Moreover, the autophagy marker p62 is significantly increased. However, the lysosomal-associated membrane protein-2 (Lamp-2), a protein that is required for the proper fusion of autophagosomes with lysosomes, is decreased in acute pancreatitis. These results suggest that a crucial role for autophagy and Lamp-2 in the pathogenesis of acute pancreatitis.

Conclusions: Our data suggest that the autophagic flux is impaired in acute pancreatitis. The depletion of Lamp-2 may play a role in the pathogenesis of acute pancreatitis.

Keywords: Acute pancreatitis; L-arginine; Lamp-2; autophagy; p62.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Arginine*
  • Autophagy*
  • Biomarkers / metabolism
  • Blotting, Western
  • Disease Models, Animal
  • Heat-Shock Proteins / metabolism
  • Lysosomal-Associated Membrane Protein 2 / metabolism
  • Lysosomes / metabolism
  • Lysosomes / pathology*
  • Lysosomes / ultrastructure
  • Male
  • Membrane Fusion*
  • Mice
  • Microscopy, Electron, Scanning
  • Pancreas / metabolism
  • Pancreas / pathology*
  • Pancreas / ultrastructure
  • Pancreatitis / chemically induced*
  • Pancreatitis / metabolism
  • Pancreatitis / pathology*
  • Sequestosome-1 Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Heat-Shock Proteins
  • Lysosomal-Associated Membrane Protein 2
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • Arginine