C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death
Protein & Cell
; (12): 1013-1026, 2018.
Article
en En
| WPRIM
| ID: wpr-757971
Biblioteca responsable:
WPRO
ABSTRACT
Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A-D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.
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Texto completo:
1
Índice:
WPRIM
Asunto principal:
Patología
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Farmacología
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Células HeLa
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Transducción de Señal
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Supervivencia Celular
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Muerte Celular
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Caenorhabditis elegans
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Biología Celular
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Alcaloides
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Factor de Transcripción STAT3
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Protein & Cell
Año:
2018
Tipo del documento:
Article