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http://purl.uniprot.org/citations/20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20544854http://www.w3.org/2000/01/rdf-schema#comment"Cellular zinc plays a key role in lysosomal change and cell death in neurons and astrocytes under oxidative stress. Here, using astrocytes lacking metallothionein-3 (MT3), a potential source of labile zinc in the brain, we studied the role of MT3 in oxidative stress responses. H(2)O(2) induced a large increase in labile zinc in wild-type (WT) astrocytes, but stimulated only a modest rise in MT3-null astrocytes. In addition, H(2)O(2)-induced lysosomal membrane permeabilization (LMP) and cell death were comparably attenuated in MT3-null astrocytes. Expression and glycosylation of Lamp1 (lysosome-associated membrane protein 1) and Lamp2 were increased in MT3-null astrocytes, and the activities of several lysosomal enzymes were significantly reduced, indicating an effect of MT3 on lysosomal components. Consistent with lysosomal dysfunction in MT3-null cells, the level of LC3-II (microtubule-associated protein 1 light chain 3), a marker of early autophagy, was increased by oxidative stress in WT astrocytes, but not in MT3-null cells. Similar changes in Lamp1, LC3, and cathepsin-D were induced by the lysosomal inhibitors bafilomycin A1, chloroquine, and monensin, indicating that lysosomal dysfunction may lie upstream of changes observed in MT3-null astrocytes. Consistent with this idea, lysosomal accumulation of cholesterol and lipofuscin were augmented in MT3-null astrocytes. Similar to the results seen in MT3-null cells, MT3 knockdown by siRNA inhibited oxidative stress-induced increases in zinc and LMP. These results indicate that MT3 may play a key role in normal lysosomal function in cultured astrocytes."xsd:string
http://purl.uniprot.org/citations/20544854http://purl.org/dc/terms/identifier"doi:10.1002/glia.20998"xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/author"Kim H.J."xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/author"Park M.H."xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/author"Koh J.Y."xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/name"Glia"xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/pages"1186-1196"xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/title"Metallothionein-3 regulates lysosomal function in cultured astrocytes under both normal and oxidative conditions."xsd:string
http://purl.uniprot.org/citations/20544854http://purl.uniprot.org/core/volume"58"xsd:string
http://purl.uniprot.org/citations/20544854http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20544854
http://purl.uniprot.org/citations/20544854http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20544854
http://purl.uniprot.org/uniprot/P28184#attribution-135701E641694F0A772E6A10A6AEB96Ahttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_A0A1D5RLC3-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_A0A1D5RLF4-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_A0A1D5RLI5-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_A0A1D5RLN7-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_A0A1D5RMG1-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_P28184-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_Q3USP9-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_P02798-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_P02802-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854
http://purl.uniprot.org/uniprot/#_Q3U340-mappedCitation-20544854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20544854