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Article: Expression of ZnT and ZIP zinc transporters in the human RPE and their regulation by neurotrophic factors

TitleExpression of ZnT and ZIP zinc transporters in the human RPE and their regulation by neurotrophic factors
Authors
Issue Date2008
PublisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org
Citation
Investigative Ophthalmology And Visual Science, 2008, v. 49 n. 3, p. 1221-1231 How to Cite?
AbstractPURPOSE. Zinc is an essential cofactor for normal cell function. Altered expression and function of zinc transporters may contribute to the pathogenesis of neurodegenerative disorders including macular degeneration. The expression and regulation of zinc transporters in the RPE and the toxicity of zinc to these cells were examined. METHODS. Zinc transporters were identified in a human RPE cell line, ARPE19, using a 28K human array, and their expression was confirmed by PCR, immunocytochemistry, and Western blot analysis in primary human RPE cultures and ARPE19. Zinc toxicity to ARPE19 was determined using monotetrazolium, propidium iodide, and TUNEL assays, and Zn 2+ uptake was visualized with Zinquin ethyl ester. The effect of various growth factors on zinc transporter expression also was examined. RESULTS. Transcripts for 20 of 23 zinc transporters are expressed in fetal human RPE, 16 of 23 in adult human RPE, and 21 of 23 in ARPE19. Zn transporter proteins were also detected in ARPE19. ZnT5 expression was not observed, whereas ZnT6, ZIP1, and ZIP13 were the most abundantly expressed in all RPE samples. The addition of low concentrations of Zn 2+ to cultures resulted in a dose-dependent increase in intracellular Zn 2+ content in ARPE19, and >30 nM Zn 2+ induced necrosis with an LC 50 of 117.4 nM. Brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor (GDNF), and pigment epithelial-derived neurotrophic factor (PEDF) increased ZIP2 expression, GDNF and PEDF increased ZnT2 expression, and PEDF increased ZnT3 and ZnT8 expression. These neurotrophic factors also promoted Zn 2+ uptake in the RPE. CONCLUSIONS. The array of zinc transporters expressed by the RPE may play a key role in zinc homeostasis in the retina and in ocular health and diseases. Copyright © Association for Research in Vision and Ophthalmology.
Persistent Identifierhttp://hdl.handle.net/10722/169852
ISSN
2015 Impact Factor: 3.427
2015 SCImago Journal Rankings: 2.008
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, KWen_HK
dc.contributor.authorLiu, Men_HK
dc.contributor.authorXu, Men_HK
dc.contributor.authorSeiler, MJen_HK
dc.contributor.authorBarnstable, CJen_HK
dc.contributor.authorTombranTink, Jen_HK
dc.date.accessioned2012-10-25T04:57:04Z-
dc.date.available2012-10-25T04:57:04Z-
dc.date.issued2008en_HK
dc.identifier.citationInvestigative Ophthalmology And Visual Science, 2008, v. 49 n. 3, p. 1221-1231en_HK
dc.identifier.issn0146-0404en_HK
dc.identifier.urihttp://hdl.handle.net/10722/169852-
dc.description.abstractPURPOSE. Zinc is an essential cofactor for normal cell function. Altered expression and function of zinc transporters may contribute to the pathogenesis of neurodegenerative disorders including macular degeneration. The expression and regulation of zinc transporters in the RPE and the toxicity of zinc to these cells were examined. METHODS. Zinc transporters were identified in a human RPE cell line, ARPE19, using a 28K human array, and their expression was confirmed by PCR, immunocytochemistry, and Western blot analysis in primary human RPE cultures and ARPE19. Zinc toxicity to ARPE19 was determined using monotetrazolium, propidium iodide, and TUNEL assays, and Zn 2+ uptake was visualized with Zinquin ethyl ester. The effect of various growth factors on zinc transporter expression also was examined. RESULTS. Transcripts for 20 of 23 zinc transporters are expressed in fetal human RPE, 16 of 23 in adult human RPE, and 21 of 23 in ARPE19. Zn transporter proteins were also detected in ARPE19. ZnT5 expression was not observed, whereas ZnT6, ZIP1, and ZIP13 were the most abundantly expressed in all RPE samples. The addition of low concentrations of Zn 2+ to cultures resulted in a dose-dependent increase in intracellular Zn 2+ content in ARPE19, and >30 nM Zn 2+ induced necrosis with an LC 50 of 117.4 nM. Brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor (GDNF), and pigment epithelial-derived neurotrophic factor (PEDF) increased ZIP2 expression, GDNF and PEDF increased ZnT2 expression, and PEDF increased ZnT3 and ZnT8 expression. These neurotrophic factors also promoted Zn 2+ uptake in the RPE. CONCLUSIONS. The array of zinc transporters expressed by the RPE may play a key role in zinc homeostasis in the retina and in ocular health and diseases. Copyright © Association for Research in Vision and Ophthalmology.en_HK
dc.languageengen_US
dc.publisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.orgen_HK
dc.relation.ispartofInvestigative Ophthalmology and Visual Scienceen_HK
dc.titleExpression of ZnT and ZIP zinc transporters in the human RPE and their regulation by neurotrophic factorsen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, KW: kwleung1@hku.hken_HK
dc.identifier.authorityLeung, KW=rp01674en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1167/iovs.07-0781en_HK
dc.identifier.pmid18326752-
dc.identifier.scopuseid_2-s2.0-41949107655en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-41949107655&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1221en_HK
dc.identifier.epage1231en_HK
dc.identifier.isiWOS:000253812900054-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, KW=13106059300en_HK
dc.identifier.scopusauthoridLiu, M=11939323400en_HK
dc.identifier.scopusauthoridXu, M=7403607640en_HK
dc.identifier.scopusauthoridSeiler, MJ=7006151950en_HK
dc.identifier.scopusauthoridBarnstable, CJ=7006293072en_HK
dc.identifier.scopusauthoridTombranTink, J=7003724753en_HK

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