Zn2+ efflux through lysosomal exocytosis prevents Zn2+-induced toxicity.
Identifieur interne : 000758 ( Main/Exploration ); précédent : 000757; suivant : 000759Zn2+ efflux through lysosomal exocytosis prevents Zn2+-induced toxicity.
Auteurs : Ira Kukic [États-Unis] ; Shannon L. Kelleher [États-Unis] ; Kirill Kiselyov [États-Unis]Source :
- Journal of cell science [ 1477-9137 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
- métabolisme : Lysosomes, Zinc.
- pharmacologie : Macrolides.
- physiologie : Exocytose, Mort cellulaire.
- toxicité : Zinc.
- Cellules HeLa, Exocytose, Humains, Mort cellulaire, Transfection.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Zinc.
- chemical , pharmacology : Macrolides.
- drug effects : Cell Death, Exocytosis.
- metabolism : Lysosomes.
- physiology : Cell Death, Exocytosis.
- chemical , toxicity : Zinc.
- HeLa Cells, Humans, Transfection.
Abstract
Zn(2+) is an essential micronutrient and an important ionic signal whose excess, as well as scarcity, is detrimental to cells. Free cytoplasmic Zn(2+) is controlled by a network of Zn(2+) transporters and chelating proteins. Recently, lysosomes became the focus of studies in Zn(2+) transport, as they were shown to play a role in Zn(2+)-induced toxicity by serving as Zn(2+) sinks that absorb Zn(2+) from the cytoplasm. Here, we investigated the impact of the lysosomal Zn(2+) sink on the net cellular Zn(2+) distribution and its role in cell death. We found that lysosomes played a cytoprotective role during exposure to extracellular Zn(2+). Such a role required lysosomal acidification and exocytosis. Specifically, we found that the inhibition of lysosomal acidification using Bafilomycin A1 (Baf) led to a redistribution of Zn(2+) pools and increased apoptosis. Additionally, the inhibition of lysosomal exocytosis through knockdown (KD) of the lysosomal SNARE proteins VAMP7 and synaptotagmin VII (SYT7) suppressed Zn(2+) secretion and VAMP7 KD cells had increased apoptosis. These data show that lysosomes play a central role in Zn(2+) handling, suggesting that there is a new Zn(2+) detoxification pathway.
DOI: 10.1242/jcs.145318
PubMed: 24829149
Affiliations:
- États-Unis
- Pennsylvanie
- Pittsburgh, University Park (Pennsylvanie)
- Université d'État de Pennsylvanie, Université de Pittsburgh
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Le document en format XML
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Free cytoplasmic Zn(2+) is controlled by a network of Zn(2+) transporters and chelating proteins. Recently, lysosomes became the focus of studies in Zn(2+) transport, as they were shown to play a role in Zn(2+)-induced toxicity by serving as Zn(2+) sinks that absorb Zn(2+) from the cytoplasm. Here, we investigated the impact of the lysosomal Zn(2+) sink on the net cellular Zn(2+) distribution and its role in cell death. We found that lysosomes played a cytoprotective role during exposure to extracellular Zn(2+). Such a role required lysosomal acidification and exocytosis. Specifically, we found that the inhibition of lysosomal acidification using Bafilomycin A1 (Baf) led to a redistribution of Zn(2+) pools and increased apoptosis. Additionally, the inhibition of lysosomal exocytosis through knockdown (KD) of the lysosomal SNARE proteins VAMP7 and synaptotagmin VII (SYT7) suppressed Zn(2+) secretion and VAMP7 KD cells had increased apoptosis. These data show that lysosomes play a central role in Zn(2+) handling, suggesting that there is a new Zn(2+) detoxification pathway.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li><li>University Park (Pennsylvanie)</li></settlement><orgName><li>Université d'État de Pennsylvanie</li><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Kukic, Ira" sort="Kukic, Ira" uniqKey="Kukic I" first="Ira" last="Kukic">Ira Kukic</name></region><name sortKey="Kelleher, Shannon L" sort="Kelleher, Shannon L" uniqKey="Kelleher S" first="Shannon L" last="Kelleher">Shannon L. Kelleher</name><name sortKey="Kiselyov, Kirill" sort="Kiselyov, Kirill" uniqKey="Kiselyov K" first="Kirill" last="Kiselyov">Kirill Kiselyov</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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