Metal- and tissue-dependent relationship between metallothionein mRNA and protein

M H Vasconcelos, S C Tam, J E Hesketh, M Reid, J H Beattie

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    Abstract

    Metallothionein (MT) expression is transcriptionally regulated but recent evidence suggests that translation of MT mRNA may be regulated under some circumstances (Vasconcelos et al., Biochem. J., 315, 665-671, 1996). A systematic investigation of MT mRNA, protein, and metal levels in liver and kidney of cadmium- or copper-treated rats was made to further understand the relationship between mRNA and protein in particular. Adult rats were injected once with either Cd (8.9 mumol/kg) or Cu2+ (8.7 mumol/kg) as the chloride salts, and the liver and kidney concentrations of MT-1 and MT-2 mRNA, total soluble MT protein, and tissue Cd, Cu, and Zn were monitored over 48-72 h. The metal composition in the soluble MT protein fraction was also analyzed by on-line size-exclusion chromatography-ICP/MS. Discrepancies between mRNA and protein levels were found in both tissues, but particularly in kidney. Cd treatment significantly increased renal MT-1 and MT-2 mRNA levels but protein was unaffected. In contrast, Cu actually decreased renal MT-1 and MT-2 mRNA but significantly increased MT protein. Cd induced considerably more MT-1 than MT-2 mRNA in liver, but induction of both isoforms was similar in kidney and in liver of Cu-treated rats. Changes in tissue metal levels tended to reflect MT protein levels and Cd appeared to bind to existing MT in the kidney. The results support the contention that MT protein levels often bear no clear relationship with mRNA levels and emphasizes the importance of measuring both in studies of MT expression. (C) 2002 Elsevier Science (USA).

    Original languageEnglish
    Pages (from-to)91-97
    Number of pages7
    JournalToxicology and Applied Pharmacology
    Volume182
    DOIs
    Publication statusPublished - 2002

    Keywords

    • metallothionein
    • cadmium
    • copper
    • PLASMA MASS-SPECTROMETRY
    • MESSENGER-RNA
    • POSTTRANSCRIPTIONAL REGULATION
    • RAT-LIVER
    • INDUCTION
    • CADMIUM
    • COPPER
    • ZINC
    • ACCUMULATION
    • ISOFORMS

    Cite this

    Metal- and tissue-dependent relationship between metallothionein mRNA and protein. / Vasconcelos, M H ; Tam, S C ; Hesketh, J E ; Reid, M ; Beattie, J H .

    In: Toxicology and Applied Pharmacology, Vol. 182, 2002, p. 91-97.

    Research output: Contribution to journalArticle

    Vasconcelos, M H ; Tam, S C ; Hesketh, J E ; Reid, M ; Beattie, J H . / Metal- and tissue-dependent relationship between metallothionein mRNA and protein. In: Toxicology and Applied Pharmacology. 2002 ; Vol. 182. pp. 91-97.
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    AU - Vasconcelos, M H

    AU - Tam, S C

    AU - Hesketh, J E

    AU - Reid, M

    AU - Beattie, J H

    PY - 2002

    Y1 - 2002

    N2 - Metallothionein (MT) expression is transcriptionally regulated but recent evidence suggests that translation of MT mRNA may be regulated under some circumstances (Vasconcelos et al., Biochem. J., 315, 665-671, 1996). A systematic investigation of MT mRNA, protein, and metal levels in liver and kidney of cadmium- or copper-treated rats was made to further understand the relationship between mRNA and protein in particular. Adult rats were injected once with either Cd (8.9 mumol/kg) or Cu2+ (8.7 mumol/kg) as the chloride salts, and the liver and kidney concentrations of MT-1 and MT-2 mRNA, total soluble MT protein, and tissue Cd, Cu, and Zn were monitored over 48-72 h. The metal composition in the soluble MT protein fraction was also analyzed by on-line size-exclusion chromatography-ICP/MS. Discrepancies between mRNA and protein levels were found in both tissues, but particularly in kidney. Cd treatment significantly increased renal MT-1 and MT-2 mRNA levels but protein was unaffected. In contrast, Cu actually decreased renal MT-1 and MT-2 mRNA but significantly increased MT protein. Cd induced considerably more MT-1 than MT-2 mRNA in liver, but induction of both isoforms was similar in kidney and in liver of Cu-treated rats. Changes in tissue metal levels tended to reflect MT protein levels and Cd appeared to bind to existing MT in the kidney. The results support the contention that MT protein levels often bear no clear relationship with mRNA levels and emphasizes the importance of measuring both in studies of MT expression. (C) 2002 Elsevier Science (USA).

    AB - Metallothionein (MT) expression is transcriptionally regulated but recent evidence suggests that translation of MT mRNA may be regulated under some circumstances (Vasconcelos et al., Biochem. J., 315, 665-671, 1996). A systematic investigation of MT mRNA, protein, and metal levels in liver and kidney of cadmium- or copper-treated rats was made to further understand the relationship between mRNA and protein in particular. Adult rats were injected once with either Cd (8.9 mumol/kg) or Cu2+ (8.7 mumol/kg) as the chloride salts, and the liver and kidney concentrations of MT-1 and MT-2 mRNA, total soluble MT protein, and tissue Cd, Cu, and Zn were monitored over 48-72 h. The metal composition in the soluble MT protein fraction was also analyzed by on-line size-exclusion chromatography-ICP/MS. Discrepancies between mRNA and protein levels were found in both tissues, but particularly in kidney. Cd treatment significantly increased renal MT-1 and MT-2 mRNA levels but protein was unaffected. In contrast, Cu actually decreased renal MT-1 and MT-2 mRNA but significantly increased MT protein. Cd induced considerably more MT-1 than MT-2 mRNA in liver, but induction of both isoforms was similar in kidney and in liver of Cu-treated rats. Changes in tissue metal levels tended to reflect MT protein levels and Cd appeared to bind to existing MT in the kidney. The results support the contention that MT protein levels often bear no clear relationship with mRNA levels and emphasizes the importance of measuring both in studies of MT expression. (C) 2002 Elsevier Science (USA).

    KW - metallothionein

    KW - cadmium

    KW - copper

    KW - PLASMA MASS-SPECTROMETRY

    KW - MESSENGER-RNA

    KW - POSTTRANSCRIPTIONAL REGULATION

    KW - RAT-LIVER

    KW - INDUCTION

    KW - CADMIUM

    KW - COPPER

    KW - ZINC

    KW - ACCUMULATION

    KW - ISOFORMS

    U2 - 10.1006/taap.2002.9428

    DO - 10.1006/taap.2002.9428

    M3 - Article

    VL - 182

    SP - 91

    EP - 97

    JO - Toxicology and Applied Pharmacology

    JF - Toxicology and Applied Pharmacology

    SN - 0041-008X

    ER -