| RRC ID |
63438
|
| Author |
Yamada D, Saiki S, Furuya N, Ishikawa K, Imamichi Y, Kambe T, Fujimura T, Ueno T, Koike M, Sumiyoshi K, Hattori N.
|
| Title |
Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
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.
|
| Volume |
471(1)
|
| Pages |
109-16
|
| Published |
2016-2-26
|
| DOI |
10.1016/j.bbrc.2016.01.171
|
| PII |
S0006-291X(16)30171-1
|
| PMID |
26851368
|
| MeSH |
Animals
Antitubercular Agents / administration & dosage*
Cell Line, Tumor
Dose-Response Relationship, Drug
Ethambutol / administration & dosage*
HeLa Cells
Humans
Lysosomes / drug effects
Lysosomes / physiology*
Lysosomes / ultrastructure
Metabolic Clearance Rate / drug effects
Phagosomes / drug effects
Phagosomes / physiology*
Phagosomes / ultrastructure
Rats
Zinc / pharmacokinetics*
|
| IF |
2.985
|
| Resource |
| Human and Animal Cells |
Huh-7 |
