Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells.
Zinc transporters are solute carrier family members. To date, 10 zinc transporters (ZnTs) and 14 Zrt-, Irt-like proteins (ZIPs) have been identified. ZnTs control intracellular zinc levels by effluxing zinc from the cytoplasm into the extracellular fluid, intracellular vesicles, and organelles; ZIPs...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5094758?pdf=render |
| _version_ | 1811321045854978048 |
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| author | Takumi Ishida Shinji Takechi |
| author_facet | Takumi Ishida Shinji Takechi |
| author_sort | Takumi Ishida |
| collection | DOAJ |
| description | Zinc transporters are solute carrier family members. To date, 10 zinc transporters (ZnTs) and 14 Zrt-, Irt-like proteins (ZIPs) have been identified. ZnTs control intracellular zinc levels by effluxing zinc from the cytoplasm into the extracellular fluid, intracellular vesicles, and organelles; ZIPs also contribute to control intracellular zinc levels with influxing zinc into the cytoplasm. Recently, changes in zinc transporter expression have been observed in some stress-induced diseases, such as Alzheimer's disease and diabetes mellitus. However, little is known regarding the mechanisms that regulate zinc transporter expression. To address this, we have investigated the effect of a well-established stress response pathway, the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway, on zinc transporter mRNA levels. Exposure to 10-4 M tert-butylhydroquinone (t-BHQ), which activates Nrf2-ARE signaling, for 6 h significantly increases ZnT-1, ZnT-3, and ZnT-6 mRNAs levels, and significantly decreases ZnT-10 and ZIP-3 mRNA levels. These changes are not observed with 10-6 M t-BHQ, which does not activate Nrf2-ARE signaling. Furthermore, t-BHQ exposure does not affect metal responsive element transcription, a cis element that is activated in response to intracellular free zinc accumulation. From these results, we believe that the transcription of ZnT-1, ZnT-3, ZnT-6, ZnT-10, and ZIP-3 is influenced by the Nrf2-ARE signal transduction pathway. |
| first_indexed | 2024-04-13T13:11:17Z |
| format | Article |
| id | doaj.art-eb8e9de7892c4498bfc80032d167fc13 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:11:17Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-eb8e9de7892c4498bfc80032d167fc132022-12-22T02:45:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011111e016610010.1371/journal.pone.0166100Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells.Takumi IshidaShinji TakechiZinc transporters are solute carrier family members. To date, 10 zinc transporters (ZnTs) and 14 Zrt-, Irt-like proteins (ZIPs) have been identified. ZnTs control intracellular zinc levels by effluxing zinc from the cytoplasm into the extracellular fluid, intracellular vesicles, and organelles; ZIPs also contribute to control intracellular zinc levels with influxing zinc into the cytoplasm. Recently, changes in zinc transporter expression have been observed in some stress-induced diseases, such as Alzheimer's disease and diabetes mellitus. However, little is known regarding the mechanisms that regulate zinc transporter expression. To address this, we have investigated the effect of a well-established stress response pathway, the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway, on zinc transporter mRNA levels. Exposure to 10-4 M tert-butylhydroquinone (t-BHQ), which activates Nrf2-ARE signaling, for 6 h significantly increases ZnT-1, ZnT-3, and ZnT-6 mRNAs levels, and significantly decreases ZnT-10 and ZIP-3 mRNA levels. These changes are not observed with 10-6 M t-BHQ, which does not activate Nrf2-ARE signaling. Furthermore, t-BHQ exposure does not affect metal responsive element transcription, a cis element that is activated in response to intracellular free zinc accumulation. From these results, we believe that the transcription of ZnT-1, ZnT-3, ZnT-6, ZnT-10, and ZIP-3 is influenced by the Nrf2-ARE signal transduction pathway.http://europepmc.org/articles/PMC5094758?pdf=render |
| spellingShingle | Takumi Ishida Shinji Takechi Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells. PLoS ONE |
| title | Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells. |
| title_full | Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells. |
| title_fullStr | Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells. |
| title_full_unstemmed | Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells. |
| title_short | Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells. |
| title_sort | nrf2 are dependent alterations in zinc transporter mrna expression in hepg2 cells |
| url | http://europepmc.org/articles/PMC5094758?pdf=render |
| work_keys_str_mv | AT takumiishida nrf2aredependentalterationsinzinctransportermrnaexpressioninhepg2cells AT shinjitakechi nrf2aredependentalterationsinzinctransportermrnaexpressioninhepg2cells |