Sex-dependent expression of metallothioneins MT1 and MT2 and concentrations of trace elements in rat liver and kidney tissues: Effect of gonadectomy

Metallothioneins (MTs) exhibit binding affinity for several essential and toxic trace elements. Previous studies in rodents indicated sex differences in the hepatic and renal expression of MTs and concentrations of various elements. The mechanism responsible for these differences has not been resolv...

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Published inJournal of trace elements in medicine and biology Vol. 53; pp. 98 - 108
Main Authors Ljubojević, Marija, Orct, Tatjana, Micek, Vedran, Karaica, Dean, Jurasović, Jasna, Breljak, Davorka, Madunić, Ivana Vrhovac, Rašić, Dubravka, Jovanović, Ivana Novak, Peraica, Maja, Gerić, Marko, Gajski, Goran, Oguić, Saša Kralik, Rogić, Dunja, Nanić, Lucia, Rubelj, Ivica, Sabolić, Ivan
Format Journal Article
LanguageEnglish
Published Germany Elsevier GmbH 01.05.2019
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Abstract Metallothioneins (MTs) exhibit binding affinity for several essential and toxic trace elements. Previous studies in rodents indicated sex differences in the hepatic and renal expression of MTs and concentrations of various elements. The mechanism responsible for these differences has not been resolved. Here, in the liver and kidney tissues of sham-operated and gonadectomized male and female rats we determined the expression of MT1 and MT2 (MT1&2) mRNA by RT-PCR, abundance of MT1&2 proteins by Western blotting and immunocytochemistry, concentrations of essential (Fe, Zn, Cu, Co) and toxic (Cd, Hg, Pb) elements by ICP-MS, and oxidative status parameters (SOD, GPx, MDA, GSH) by biochemical methods. In both organs, the expression of MT1&2 mRNA and MT1&2 proteins was female-dominant, upregulated by castration, and downregulated by ovariectomy. Concentrations of Fe in the liver and Co in the kidneys followed the same pattern. Most other elements (Zn, Cu, Cd, Hg) exhibited female- or male-dominant sex differences, affected by gonadectomy in one or both organs. Pb was sex- and gonadectomy-unaffected. GPx and MDA were elevated and associated with the highest concentrations of Fe only in the female liver. We conclude that the sex-dependent expression of MT1&2 mRNA and proteins in the rat liver and kidneys may include different mechanisms. In the liver, the female-dominant tissue concentrations of Fe may generate oxidative stress which is a potent enhancer of MTs production, whereas in kidneys, the female-dominant expression of MTs may be unrelated to Fe-mediated oxidative stress.
AbstractList Metallothioneins (MTs) exhibit binding affinity for several essential and toxic trace elements. Previous studies in rodents indicated sex differences in the hepatic and renal expression of MTs and concentrations of various elements. The mechanism responsible for these differences has not been resolved. Here, in the liver and kidney tissues of sham-operated and gonadectomized male and female rats we determined the expression of MT1 and MT2 (MT1&2) mRNA by RT-PCR, abundance of MT1&2 proteins by Western blotting and immunocytochemistry, concentrations of essential (Fe, Zn, Cu, Co) and toxic (Cd, Hg, Pb) elements by ICP-MS, and oxidative status parameters (SOD, GPx, MDA, GSH) by biochemical methods. In both organs, the expression of MT1&2 mRNA and MT1&2 proteins was female-dominant, upregulated by castration, and downregulated by ovariectomy. Concentrations of Fe in the liver and Co in the kidneys followed the same pattern. Most other elements (Zn, Cu, Cd, Hg) exhibited female- or male-dominant sex differences, affected by gonadectomy in one or both organs. Pb was sex- and gonadectomy-unaffected. GPx and MDA were elevated and associated with the highest concentrations of Fe only in the female liver. We conclude that the sex-dependent expression of MT1&2 mRNA and proteins in the rat liver and kidneys may include different mechanisms. In the liver, the female-dominant tissue concentrations of Fe may generate oxidative stress which is a potent enhancer of MTs production, whereas in kidneys, the female-dominant expression of MTs may be unrelated to Fe-mediated oxidative stress.
Author Madunić, Ivana Vrhovac
Rašić, Dubravka
Breljak, Davorka
Micek, Vedran
Gerić, Marko
Oguić, Saša Kralik
Peraica, Maja
Jovanović, Ivana Novak
Rubelj, Ivica
Gajski, Goran
Nanić, Lucia
Sabolić, Ivan
Ljubojević, Marija
Orct, Tatjana
Karaica, Dean
Jurasović, Jasna
Rogić, Dunja
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  givenname: Ivana Vrhovac
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  givenname: Dubravka
  orcidid: 0000-0002-0677-9305
  surname: Rašić
  fullname: Rašić, Dubravka
  organization: Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
– sequence: 9
  givenname: Ivana Novak
  surname: Jovanović
  fullname: Jovanović, Ivana Novak
  organization: Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
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  givenname: Maja
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  fullname: Peraica, Maja
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  givenname: Marko
  surname: Gerić
  fullname: Gerić, Marko
  organization: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
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  givenname: Goran
  surname: Gajski
  fullname: Gajski, Goran
  organization: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
– sequence: 13
  givenname: Saša Kralik
  surname: Oguić
  fullname: Oguić, Saša Kralik
  organization: Clinical Institute of Laboratory Diagnostics, Clinical Hospital Center, Zagreb, Croatia
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  givenname: Dunja
  surname: Rogić
  fullname: Rogić, Dunja
  organization: Clinical Institute of Laboratory Diagnostics, Clinical Hospital Center, Zagreb, Croatia
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  givenname: Lucia
  orcidid: 0000-0003-3413-5731
  surname: Nanić
  fullname: Nanić, Lucia
  organization: Laboratory for Molecular and Cellular Biology, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia
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  givenname: Ivica
  surname: Rubelj
  fullname: Rubelj, Ivica
  organization: Laboratory for Molecular and Cellular Biology, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia
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  givenname: Ivan
  surname: Sabolić
  fullname: Sabolić, Ivan
  email: sabolic@imi.hr
  organization: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
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Immunocytochemistry
End-point RT-PCR
PFA
MDA
Western blotting
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BSA
RNS
Oxidative status
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PBS
MT-ab
SOD
Sex differences
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Snippet Metallothioneins (MTs) exhibit binding affinity for several essential and toxic trace elements. Previous studies in rodents indicated sex differences in the...
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SubjectTerms End-point RT-PCR
ICP-MS
Immunocytochemistry
Oxidative status
Sex differences
Sex hormones
Western blotting
Title Sex-dependent expression of metallothioneins MT1 and MT2 and concentrations of trace elements in rat liver and kidney tissues: Effect of gonadectomy
URI https://dx.doi.org/10.1016/j.jtemb.2019.02.010
https://www.ncbi.nlm.nih.gov/pubmed/30910215
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