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Pentavalent vanadium induces hepatic metallothionein through interleukin-6-dependent and -independent mechanisms.
- Source :
-
Toxicology [Toxicology] 2006 Dec 07; Vol. 228 (2-3), pp. 162-70. Date of Electronic Publication: 2006 Aug 24. - Publication Year :
- 2006
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Abstract
- Metallothionein (MT) is a low-molecular-weight cysteine-rich protein which has a high affinity for metals. The synthesis of MT is induced by heavy metals such as cadmium and zinc. However, little is known about the induction of MT by tetravalent or pentavalent metals. We investigated the induction of MT synthesis by a pentavalent vanadium compound in mice. Hepatic MT concentrations were increased by subcutaneous injection of ammonium metavanadate (AMV) dose-dependently, and to the similar levels as those induced by zinc chloride. However, accumulation of vanadium in the liver was very low, while high concentrations of vanadium were detected in the kidney. High performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) chromatogram of the liver cytosol of AMV-treated mice revealed that the major metal bound to MT was not vanadium, but zinc. The chromatogram of the liver cytosol of MT null mice demonstrated the existence of a low-molecular-weight vanadium-binding protein that is different from MT. A time-course study showed that concentrations of serum interleukin-6 (IL-6) and serum amyloid A (SAA), an acute-phase protein, increased after the AMV injection. To confirm the involvement of IL-6 in MT induction by AMV administration, IL-6 null and wild-type mice were injected with AMV. In IL-6 null mice, hepatic MT induction by AMV administration decreased significantly to about a half of wild-type mice. These data suggest that both IL-6-dependent and -independent mechanisms are involved in MT induction by vanadium compounds in mice.
- Subjects :
- Alanine Transaminase metabolism
Amyloid blood
Animals
Aspartate Aminotransferases metabolism
Chromatography, High Pressure Liquid
Cytosol drug effects
Cytosol metabolism
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Kidney metabolism
Liver drug effects
Male
Mass Spectrometry
Metals metabolism
Mice
Mice, Inbred ICR
Mice, Knockout
Tissue Distribution
Vanadium metabolism
Interleukin-6 physiology
Liver metabolism
Metallothionein metabolism
Vanadates toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0300-483X
- Volume :
- 228
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 16987576
- Full Text :
- https://doi.org/10.1016/j.tox.2006.08.022