The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy.
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.
Suzuki
Takashi
T
Department of Life Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902.
Nakagawa
Masahiro
M
Yoshikawa
Ayumu
A
Sasagawa
Noboru
N
Yoshimori
Tamotsu
T
Ohsumi
Yoshinori
Y
Nishino
Ichizo
I
Ishiura
Shoichi
S
Nonaka
Ikuya
I
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D019556:COS Cells; D002738:Chloroquine / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000473:pathology*; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational; D051381:Rats; D013997:Time Factors; D014162:Transfection; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D008869:Microtubule-Associated Proteins; D002738:Chloroquine