Accumulation of tau in autophagic vacuoles in chloroquine myopathy.
Long-term administration of chloroquine to rats induces a vacuolar myopathy, which is specifically termed chloroquine myopathy (CM). In CM, tau mRNA levels were transiently upregulated in the early phase, while tau itself slowly accumulated in the late phase. The temporal profiles of tau mRNA levels and its accumulation were very similar to those of beta-amyloid protein precursor (APP) and its carboxyl-terminal fragments, both of which have been known to be degraded in lysosomes. Immunocytochemistry showed that tau progressively accumulated in the rimmed vacuoles exhibiting increased acid phosphatase activities, and immunoelectron microscopy demonstrated that tau was located within autophagic vacuoles. These results suggest that the accumulation of tau in CM is due to defective tau degradation in the lysosomal compartment in the muscle.
Murakami
N
N
Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.
Oyama
F
F
Gu
Y
Y
McLennan
I S
IS
Nonaka
I
I
Ihara
Y
Y
D000135:Acid Phosphatase / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis; D000818:Animals; D001343:Autophagy; D002738:Chloroquine / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016253:Microscopy, Immunoelectron; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D014617:Vacuoles / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016875:tau Proteins / Q000096:biosynthesis*
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D016875:tau Proteins; D002738:Chloroquine; D000135:Acid Phosphatase