GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia
Choroid plexus (CP) sequesters cadmium and other metals, protecting the brain from these neurotoxins. These metals can induce cellular stress and modulate homeostatic functions of CP, such as solute transport. We previously showed in primary cultured neonatal rat CP epithelial cells (CPECs) that cad...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8857 |
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| author | Samantha D. Francis Stuart Alice R. Villalobos |
| author_facet | Samantha D. Francis Stuart Alice R. Villalobos |
| author_sort | Samantha D. Francis Stuart |
| collection | DOAJ |
| description | Choroid plexus (CP) sequesters cadmium and other metals, protecting the brain from these neurotoxins. These metals can induce cellular stress and modulate homeostatic functions of CP, such as solute transport. We previously showed in primary cultured neonatal rat CP epithelial cells (CPECs) that cadmium induced cellular stress and stimulated choline uptake at the apical membrane, which interfaces with cerebrospinal fluid in situ. Here, in CPECs, we characterized the roles of glutathione (GSH) and Zinc supplementation in the adaptive stress response to cadmium. Cadmium increased GSH and decreased the reduced GSH-to-oxidized GSH (GSSG) ratio. Heat shock protein-70 (Hsp70), heme oxygenase (HO-1), and metallothionein (Mt-1) were induced along with the catalytic and modifier subunits of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis. Inhibition of GCL by <i><span style="font-variant: small-caps;">l</span></i>-buthionine sulfoximine (BSO) enhanced stress protein induction and stimulation of choline uptake by cadmium. Zinc alone did not induce Hsp70, HO-1, or GCL subunits, or modulate choline uptake. Zinc supplementation during cadmium exposure attenuated stress protein induction and stimulation of choline uptake; this effect persisted despite inhibition of GSH synthesis. These data indicated up-regulation of GSH synthesis promotes adaptation to cadmium-induced cellular stress in CP, but Zinc may confer cytoprotection independent of GSH. |
| first_indexed | 2024-03-10T08:43:52Z |
| format | Article |
| id | doaj.art-630532c66798494696de969e3ca722c2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:43:52Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-630532c66798494696de969e3ca722c22023-11-22T08:01:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216885710.3390/ijms22168857GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus EpitheliaSamantha D. Francis Stuart0Alice R. Villalobos1Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USADepartment of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USAChoroid plexus (CP) sequesters cadmium and other metals, protecting the brain from these neurotoxins. These metals can induce cellular stress and modulate homeostatic functions of CP, such as solute transport. We previously showed in primary cultured neonatal rat CP epithelial cells (CPECs) that cadmium induced cellular stress and stimulated choline uptake at the apical membrane, which interfaces with cerebrospinal fluid in situ. Here, in CPECs, we characterized the roles of glutathione (GSH) and Zinc supplementation in the adaptive stress response to cadmium. Cadmium increased GSH and decreased the reduced GSH-to-oxidized GSH (GSSG) ratio. Heat shock protein-70 (Hsp70), heme oxygenase (HO-1), and metallothionein (Mt-1) were induced along with the catalytic and modifier subunits of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis. Inhibition of GCL by <i><span style="font-variant: small-caps;">l</span></i>-buthionine sulfoximine (BSO) enhanced stress protein induction and stimulation of choline uptake by cadmium. Zinc alone did not induce Hsp70, HO-1, or GCL subunits, or modulate choline uptake. Zinc supplementation during cadmium exposure attenuated stress protein induction and stimulation of choline uptake; this effect persisted despite inhibition of GSH synthesis. These data indicated up-regulation of GSH synthesis promotes adaptation to cadmium-induced cellular stress in CP, but Zinc may confer cytoprotection independent of GSH.https://www.mdpi.com/1422-0067/22/16/8857choroid plexuscadmiumZincGSHcholinetransport |
| spellingShingle | Samantha D. Francis Stuart Alice R. Villalobos GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia International Journal of Molecular Sciences choroid plexus cadmium Zinc GSH choline transport |
| title | GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia |
| title_full | GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia |
| title_fullStr | GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia |
| title_full_unstemmed | GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia |
| title_short | GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia |
| title_sort | gsh and zinc supplementation attenuate cadmium induced cellular stress and stimulation of choline uptake in cultured neonatal rat choroid plexus epithelia |
| topic | choroid plexus cadmium Zinc GSH choline transport |
| url | https://www.mdpi.com/1422-0067/22/16/8857 |
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