Dichotomous effects of lead acetate on the expression of metallothionein in the liver and kidney of mice.
Metallothionein (MT) is a low-molecular-weight cysteine-rich protein which has a high affinity for metals and plays important roles in the protection against metal toxicity. As little information is available concerning the mechanism of MT induction by lead (Pb) compounds, we investigated the induction of MT by Pb acetate both at mRNA and protein levels in mice. Administration of Pb increased the levels of MT-I mRNA in the liver and kidney in six strains of mice. However, MT protein was detected only in the liver, and little or no increases in MT protein were detected in the kidney of any strains of mice. Speciation of metals in the liver cytosol showed that the major metal bound to MT was zinc but not Pb. The increases in plasma concentrations of interleukin-6 suggest that the production of interleukin-6 by Pb administration is involved in the induction of MT in the liver. Treatment of renal cells with Pb in vitro also resulted in the increase in MT mRNA but little increase in MT protein. These data suggest that Pb exerts a dual effect on MT expression; enhancement of MT gene transcription both in the liver and kidney and suppression of MT mRNA translation in the kidney.
Yu
Jiaming
J
Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
Fujishiro
Hitomi
H
Miyataka
Hideki
H
Oyama
Tomohiro Max
TM
Hasegawa
Tatsuya
T
Seko
Yoshiyuki
Y
Miura
Nobuhiko
N
Himeno
Seiichiro
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D014018:Tissue Distribution
D004785:Environmental Pollutants; D015850:Interleukin-6; D009942:Organometallic Compounds; D000685:Serum Amyloid A Protein; D008668:Metallothionein; D000410:Alanine Transaminase; C008261:lead acetate