Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity
Mercury (Hg) is an important environmental toxicant to which humans are exposed on a regular basis. Mercuric ions within biological systems do not exist as free ions. Rather, they are bound to free sulfhydryl groups (thiols) on biological molecules. Metallothionein (MT) is a cysteine-rich, metal-bin...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Toxicology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X23000300 |
| _version_ | 1797397585664671744 |
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| author | Aditi Dave Lucy Joshee Delon W. Barfuss Ryan Brownlee Roha Surani Sahar Anis Ali Earl G. Ford IV Elizabeth G. Pittman Anasalea V.G. Caroland Jennifer Barkin Christy C. Bridges |
| author_facet | Aditi Dave Lucy Joshee Delon W. Barfuss Ryan Brownlee Roha Surani Sahar Anis Ali Earl G. Ford IV Elizabeth G. Pittman Anasalea V.G. Caroland Jennifer Barkin Christy C. Bridges |
| author_sort | Aditi Dave |
| collection | DOAJ |
| description | Mercury (Hg) is an important environmental toxicant to which humans are exposed on a regular basis. Mercuric ions within biological systems do not exist as free ions. Rather, they are bound to free sulfhydryl groups (thiols) on biological molecules. Metallothionein (MT) is a cysteine-rich, metal-binding protein that has been shown to bind to heavy metals and reduce their toxic effects in target cells and organs. Little is known about the effect of MT on the handing and disposition of Hg. Therefore, the current study was designed to test the hypothesis that overexpression of MT alters the corporal disposition of Hg and reduces its nephrotoxicity. Furthermore, the current study examined the transport of Hg-MT complexes in isolated proximal tubules. Rats were treated with saline or Zn followed by injection with a non-nephrotoxic (0.5 µmol kg−1), moderately nephrotoxic (1.5 µmol kg−1), or significantly nephrotoxic (2.25 µmol kg−1) dose of HgCl2 (containing radioactive Hg). Pretreatment with Zn increased mRNA expression of MT and enhanced accumulation of Hg in the renal cortex of male and female rats. In addition, injection with Zn also protected animals from Hg-induced nephrotoxicity. Studies using isolated proximal tubules from rabbit kidney demonstrated that Hg-MT is taken up rapidly at the apical and basolateral membranes. The current findings suggest that at least part of this uptake occurs through an endocytic process. This study is the first to examine the uptake of Hg-MT complexes in isolated proximal tubules. Overall, the findings of this study suggest that supplementation with Zn may be a viable strategy for reducing the risk of Hg intoxication in at-risk populations. |
| first_indexed | 2024-03-09T01:12:14Z |
| format | Article |
| id | doaj.art-fbbe915c408f4a8e8069484f665e44f8 |
| institution | Directory Open Access Journal |
| issn | 2666-027X |
| language | English |
| last_indexed | 2024-03-09T01:12:14Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj.art-fbbe915c408f4a8e8069484f665e44f82023-12-11T04:17:17ZengElsevierCurrent Research in Toxicology2666-027X2023-01-015100132Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicityAditi Dave0Lucy Joshee1Delon W. Barfuss2Ryan Brownlee3Roha Surani4Sahar Anis Ali5Earl G. Ford IV6Elizabeth G. Pittman7Anasalea V.G. Caroland8Jennifer Barkin9Christy C. Bridges10Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biology, Georgia State University, Atlanta, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USADepartment of Community Medicine, Mercer University School of Medicine, Macon, GA, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USA; Corresponding author at: 1550 College St., Macon, GA 31207, USA.Mercury (Hg) is an important environmental toxicant to which humans are exposed on a regular basis. Mercuric ions within biological systems do not exist as free ions. Rather, they are bound to free sulfhydryl groups (thiols) on biological molecules. Metallothionein (MT) is a cysteine-rich, metal-binding protein that has been shown to bind to heavy metals and reduce their toxic effects in target cells and organs. Little is known about the effect of MT on the handing and disposition of Hg. Therefore, the current study was designed to test the hypothesis that overexpression of MT alters the corporal disposition of Hg and reduces its nephrotoxicity. Furthermore, the current study examined the transport of Hg-MT complexes in isolated proximal tubules. Rats were treated with saline or Zn followed by injection with a non-nephrotoxic (0.5 µmol kg−1), moderately nephrotoxic (1.5 µmol kg−1), or significantly nephrotoxic (2.25 µmol kg−1) dose of HgCl2 (containing radioactive Hg). Pretreatment with Zn increased mRNA expression of MT and enhanced accumulation of Hg in the renal cortex of male and female rats. In addition, injection with Zn also protected animals from Hg-induced nephrotoxicity. Studies using isolated proximal tubules from rabbit kidney demonstrated that Hg-MT is taken up rapidly at the apical and basolateral membranes. The current findings suggest that at least part of this uptake occurs through an endocytic process. This study is the first to examine the uptake of Hg-MT complexes in isolated proximal tubules. Overall, the findings of this study suggest that supplementation with Zn may be a viable strategy for reducing the risk of Hg intoxication in at-risk populations.http://www.sciencedirect.com/science/article/pii/S2666027X23000300MercuryMetallothioneinKidneyNephrotoxicityHeavy metals |
| spellingShingle | Aditi Dave Lucy Joshee Delon W. Barfuss Ryan Brownlee Roha Surani Sahar Anis Ali Earl G. Ford IV Elizabeth G. Pittman Anasalea V.G. Caroland Jennifer Barkin Christy C. Bridges Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity Current Research in Toxicology Mercury Metallothionein Kidney Nephrotoxicity Heavy metals |
| title | Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity |
| title_full | Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity |
| title_fullStr | Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity |
| title_full_unstemmed | Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity |
| title_short | Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity |
| title_sort | proximal tubular transport of metallothionein mercury complexes and protection against nephrotoxicity |
| topic | Mercury Metallothionein Kidney Nephrotoxicity Heavy metals |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X23000300 |
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