Absorption and Distribution of Cadmium in Metallothionein-I Transgenic Mice

Liu, J

doi:10.1006/faat.1996.0034

Cited by 51 publications

(10 citation statements)

References 30 publications

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“…Thus, intestinal MT does not appear to be a major determinant for the dosage-dependent absorption of Cd. The minimal role of MT in Cd absorption from the gastrointestinal tract was further confirmed in studies using MT overexpressing transgenic mice (Liu and Klaassen, 1996) and with MT-null mice (Liu et al, 2001). Whereas Cd accumulation in the duodenium of MT-null mice and rats fed high Cd diets does not appear to be MT-dependent, it is affected by a marginal supply of iron (Park et al, 2002).…”

Section: Mt In CD Dispositionmentioning

confidence: 80%

“…A: Wild-type and MT-null mice were given a s.c. injection of CdCl 2 at the dose of 25 μmol (4.6 mg) Cd/kg, and liver injury was evidenced 24 hr later by increased serum ALT activity (modified from Liu et al, 1996); B: Wild-type and MT-null mice were given repeated s.c. injections of CdCl 2 at the dose of 0.1 mg/kg for 10 weeks, and liver injury was evidenced by increased liver parenchyma cell apoptosis; C: Wild-type and MT-null mice were given a single s.c. injection of CdCl 2 at the dose 5 μmol (0.92 mg) Cd/kg, and increased liver tumor incidence was only evident in MT-null mice after 2 years (modified from Waalkes and Liu, 2009). …”

Section: Figures and Tablementioning

confidence: 99%

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Metallothionein protection of cadmium toxicity

Klaassen

Liu

Diwan

2009

Toxicology and Applied Pharmacology

635

378

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The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research on this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tissues and dramatically decreases billiary excretion of Cd. Cd-bound to MT is responsible for Cd accumulation in tissues and the long biological half-life of Cd in the body. Induction of MT protects against acute Cd-induced lethality, as well as acute toxicity to the liver and lung. Intracellular MT also plays important roles in ameliorating Cd toxicity following prolonged exposures, particularly chronic Cd-induced nephrotoxicity, osteotoxicity, and toxicity to the lung, liver, and immune system. There is an association between human and rodent Cd exposure and prostate cancers, especially in the portions where MT is poorly expressed. MT expression in Cdinduced tumors varies depending on the type and the stage of tumor development. For instance, high levels of MT are detected in Cd-induced sarcomas at the injection site, whereas the sarcoma metastases were devoid of MT. The use of MT-transgenic and MT-null mice has greatly helped define the role of MT in Cd toxicology, with the MT-null mice being hypersensitive and MTtransgenic mice resistant to Cd toxicity. Thus, MT is critical for protecting human health from Cd toxicity. There are large individual variations in MT expression, which might in turn predispose some people to Cd toxicity.

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Section: Mt In CD Dispositionmentioning

confidence: 80%

Section: Figures and Tablementioning

confidence: 99%

Metallothionein protection of cadmium toxicity

Klaassen

Liu

Diwan

2009

Toxicology and Applied Pharmacology

635

378

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“…Their primary biological role remains obscure; they perform a range of functions depending on the specific needs of the particular organism or tissue and its environmental circumstance. Some of the known functions of MTs [1] include: essential-metal homeostasis [3], protection against heavy metal toxicity by sequestration [4], trapping reactive oxygen species (ROS) [5], and protection against xenobiotics [6]. In mammals, they have also been implicated in protection against neurodegenerative diseases [7] and in development and cellular differentiation processes [8].…”

Section: Introductionmentioning

confidence: 99%

Tetrahymena Metallothioneins Fall into Two Discrete Subfamilies

et al. 2007

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BackgroundMetallothioneins are ubiquitous small, cysteine-rich, multifunctional proteins which can bind heavy metals.Methodology/Principal FindingsWe report the results of phylogenetic and gene expression analyses that include two new Tetrahymena thermophila metallothionein genes (MTT3 and MTT5). Sequence alignments of all known Tetrahymena metallothioneins have allowed us to rationalize the structure of these proteins. We now formally subdivide the known metallothioneins from the ciliate genus Tetrahymena into two well defined subfamilies, 7a and 7b, based on phylogenetic analysis, on the pattern of clustering of Cys residues, and on the pattern of inducibility by the heavy metals Cd and Cu. Sequence alignment also reveals a remarkably regular, conserved and hierarchical modular structure of all five subfamily 7a MTs, which include MTT3 and MTT5. The former has three modules, while the latter has only two. Induction levels of the three T. thermophila genes were determined using quantitative real time RT-PCR. Various stressors (including heavy metals) brought about dramatically different fold-inductions for each gene; MTT5 showed the highest fold-induction. Conserved DNA motifs with potential regulatory significance were identified, in an unbiased way, upstream of the start codons of subfamily 7a MTs. EST evidence for alternative splicing in the 3′ UTR of the MTT5 mRNA with potential regulatory activity is reported.Conclusion/SignificanceThe small number and remarkably regular structure of Tetrahymena MTs, coupled with the experimental tractability of this model organism for studies of in vivo function, make it an attractive system for the experimental dissection of the roles, structure/function relationships, regulation of gene expression, and adaptive evolution of these proteins, as well as for the development of biotechnological applications for the environmental monitoring of toxic substances.

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“…Depending on the steroidogenic tissue involved and dosage administered, it enhances or inhibits the synthesis of progesterone; and antenatal exposure results in reduced birth weight and premature birth (Henson and Chedrese, 2004). Another investigation reveals that the bio-effect of Cd on mice depended on dose administered, absorption and distribution in metallothionein-1 transgenic mice (Liu and Klaassen, 1996). Malgorzata (1998) reported that Cd exposure to fishes resulted in 40% mortality 96 h after the end of the exposure due to disturbances in physiological functions in the fishes.…”

Section: Introductionmentioning

confidence: 99%

Effects of ginger (Zingiber officinale) on cadmium toxicity

Egwurugwu¹,

J²,

Ufearo³

et al. 2007

Afr. J. Biotechnol.

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Thirty six Winstar rats were divided into six equal groups and investigated for induced cadmium toxicity, and the detoxicating action of ginger on liver-accumulated cadmium. Group 1, the control, were fed with normal rat chow and water for six weeks. Group 2 were fed with normal rat chow and cadmium water (200 ppm Cd in water). Group 3 were fed with rat chow-ginger concentrate (95:5, w/w ratio) and water, while Group 4 were fed with rat chow-ginger concentrate and cadmium water, all for six weeks. Group 5 were fed with normal rat chow and cadmium water initially for one week, followed by rat chowginger concentrate and water for five weeks; while Group 6 were fed with rat chow-ginger concentrate for one week, followed by normal rat chow and cadmium water for five weeks. Cadmium accumulated highly in rat livers without ginger administration, and raised serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), while ginger lowered these parameters. Ginger had better therapeutic than prophylactic detoxication effects on liver cadmium accumulation, especially as further cadmium intake was stopped. It was concluded that cadmium detoxication by ginger was more effective therapeutically, than prophylactically, as further cadmium intake was avoided.

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Absorption and Distribution of Cadmium in Metallothionein-I Transgenic Mice

Cited by 51 publications

References 30 publications

Metallothionein protection of cadmium toxicity

Metallothionein protection of cadmium toxicity

Tetrahymena Metallothioneins Fall into Two Discrete Subfamilies

Effects of ginger (Zingiber officinale) on cadmium toxicity

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