Ethambutol is a common medicine used for the treatment of tuberculosis, which can have serious side effects, such as retinal and liver dysfunction. Although ethambutol has been reported to impair autophagic flux in rat retinal cells, the precise molecular mechanism remains unclear. Using various mammalian cell lines, we showed that ethambutol accumulated in autophagosomes and vacuolated lysosomes, with marked Zn(2+) accumulation. The enlarged lysosomes were neutralized and were infiltrated with Zn(2+) accumulations in the lysosomes, with simultaneous loss of acidification. These results suggest that EB neutralizes lysosomes leading to insufficient autophagy, implying that some of the adverse effects associated with EB in various organs may be of this mechanism.
Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation.
Daisuke Yamada,S. Saiki,Norihiko Furuya,K. Ishikawa,Yoko Imamichi,T. Kambe,T. Fujimura,T. Ueno,Masato Koike,Katsuhiko Sumiyoshi,N. Hattori
Published 2016 in Biochemical and Biophysical Research Communications - BBRC
ABSTRACT
PUBLICATION RECORD
- Publication year
2016
- Venue
Biochemical and Biophysical Research Communications - BBRC
- Publication date
2016-02-26
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
- No claims are published for this paper.
CONCEPTS
- No concepts are published for this paper.
REFERENCES
Showing 1-22 of 22 references · Page 1 of 1
CITED BY
Showing 1-15 of 15 citing papers · Page 1 of 1