The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy

J Biochem. 2002 May;131(5):647-51. doi: 10.1093/oxfordjournals.jbchem.a003147.

Abstract

Chloroquine myopathy is a drug poisoning disease involving rimmed vacuole formation. By Western blot analysis, we investigated posttranslational modification of LC3 in cultured cells with a high concentration of chloroquine, and found that the autophagosome membrane-bound form of LC3 increased dose-dependently. We also constructed a disease model by excessive chloroquine injection into rats and unusual immunohistochemical alteration was chased using anti-LC3 antibodies. With chloroquine treatment, muscle atrophy occurred predominantly in soleus muscle and unusual autophagosomes were accumulated. Therefore, we concluded that autophagy plays an important role in rimmed vacuole formation in certain muscular atrophies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Blotting, Western
  • COS Cells
  • Chloroquine / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Immunohistochemistry
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Muscular Diseases / chemically induced
  • Muscular Diseases / pathology*
  • Phagosomes / metabolism
  • Phagosomes / ultrastructure
  • Protein Processing, Post-Translational
  • Rats
  • Time Factors
  • Transfection
  • Vacuoles / drug effects
  • Vacuoles / metabolism*
  • Vacuoles / pathology

Substances

  • Microtubule-Associated Proteins
  • Chloroquine