Reduced retention of cadmium in the liver of metallothionein-null mice

Tohyama, Chiharu; Satoh, Masahiko; Kodama, Naomi; Nishimura, Hisao; Choo, Andy; Michalska, Anna; Kanayama, Yoshiharu; Naganuma, Akira

doi:10.1016/1382-6689(96)00014-2

Cited by 19 publications

(8 citation statements)

References 7 publications

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“…The role of MT in Cd disposition has been examined in MT-transgenic mice. Using this model, MT does not inhibit intestinal Cd absorption, nor does it affect initial Cd distribution to various tissues (72,73). However, MT decreases Cd elimination through the bile (74) and is a major factor for tissue retention of Cd (73,75).…”

Section: Role Of Metallothionein In Protection Against Metal Toxicitymentioning

confidence: 98%

METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity

Klaassen

Liu

Choudhuri

1999

Annu. Rev. Pharmacol. Toxicol.

1,033

738

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Metallothioneins (MT) are low-molecular-weight, cysteine-rich, metal-binding proteins. MT genes are readily induced by various physiologic and toxicologic stimuli. Because the cysteines in MT are absolutely conserved across species, it was suspected that the cysteines are necessary for function and MT is essential for life. In attempts to determine the function(s) of MT, studies have been performed using four different experimental paradigms: (a) animals injected with chemicals known to induce MT; (b) cells adapted to survive and grow in high concentrations of MT-inducing toxicants; (c) cells transfected with the MT gene; and (d) MT-transgenic and MT-null mice. Most often, results from studies using the first three approaches have indicated multiple functions of MT in cell biology: MT (a) is a "storehouse" for zinc, (b) is a free-radical scavenger, and (c) protects against cadmium (Cd) toxicity. However, studies using MT-transgenic and null mice have not strongly supported the first two proposed functions but strongly support its function in protecting against Cd toxicity. Repeated administration of Cd to MT-null mice results in nephrotoxicity at one tenth the dose that produces nephrotoxicity in control mice. Human studies indicate that 7% of the general population have renal dysfunction from Cd exposure. Therefore, if humans did not have MT, "normal" Cd exposure would be nephrotoxic to humans. Thus, it appears that during evolution, the ability of MT to protect against Cd toxicity might have taken a more pivotal role in the maintenance of life processes, as compared with its other proposed functions (i.e. storehouse for zinc and free radical scavenger).

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Section: Role Of Metallothionein In Protection Against Metal Toxicitymentioning

confidence: 98%

METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity

Klaassen

Liu

Choudhuri

1999

Annu. Rev. Pharmacol. Toxicol.

1,033

738

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“…A uniqu e as pect of cad mi um de po si ti on is that it has an ex tre mely long half-li fe in the body, on the or der of 10 to 30 ye ars in hu mans, 48 which is tho ught to be par ti ally du e to the bin ding to the pro te in me tal lot hi o ne in. 49,50 Ho we ver, the con tri bu ti on of this to xi co ki ne tic pa ra me ter to the to xi city of the compo und is unk nown. .…”

Section: Discussionmentioning

confidence: 99%

Catalase and Carbonic Anhydrase Enzyme Activities, and Some Mineral-Heavy Metal Concentrations in Newborns with Congenital Malformations

Melek¹,

Demır²,

Kırımi³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : The aim of this study is to eva lu a te the fac tors such as an ti o xi dant con di ti on and mine ral-he avy me tal le vel as so ci a ti on that may play a ro le in de ve lop ment of congenital malformations. M Ma a--t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Fif te en he althy ne o na tes as con trol gro up and 15 ne o na tes with va ri o us con ge ni tal malformations we re inc lu ded study. Eryt hrocy te cataly (CAT) which is an an ti o xi dant enz yme, eryt hrocyte carbonic anydrase (CA) enz yme ac ti vi ti es which play a im por tant ro le in acid-ba se ba lan ce, se rum copper (Cu), le ad (Pb), zinc (Zn), cad mi um (Cd), iron (Fe), man ga ne se (Mn) and mag ne si um (Mg) we re me a su red from ve no us blo od samp les of each sub ject. R Re e s su ul lt ts s: : Eryt hrocy te CAT enz yme ac ti vity, se rum Zn and Fe le vels we re sta tis ti cally sig ni fi cantly dec re a sed (P<0.05) in the study gro up whi le se rum Cu and Cd le vels we re sta tis ti cally sig ni fi cantly high (P<0.05)in the study gro up when com pa red to the con trol gro up. A ne ga ti ve cor re la ti on bet we en eryt hrocy te CA ac ti vity and se rum Pb le vels was fo und in the study gro up. In the con trol gro up, ne ga ti ve cor re la ti ons we re fo und bet we en eryt hrocy te CAT ac ti vity and se rum Pb levels; se rum Mg and Cu le vels; and se rum Cd and Mn le vels. In addition, in the con trol gro up a po si ti ve corre la ti on bet we en se rum Zn and Cu le vels; eryt hrocy te CA ac ti vity and se rum Mn le vels was fo und. C Co on nc c l lu u s si i o on n: : Our re sults suggest that eryt hrocy te CAT enz yme ac ti vity and se rum Cu, Zn, Fe and Cd le vels may play a ro le in pat ho ge ne sis of con ge ni tal malformations. The oxi da ti ve stress that ri se as a re sult of an im ba lan ce bet we en pro o xi dant and an ti o xi dant re ac ti ons se ems to be as so ci a ted with con ge ni tal malformations. Furt her stu di es are needed to con firm the as so ci a ti on of an ti o xi dant con di ti on and mi ne ral-he avy me tal le vels in the pat ho ge ne sis of con ge ni tal malformations.K Ke ey y W Wo or rd ds s: : Ca ta la se; car bo nic anhy dra ses; mi ne rals; he avy me tals; con ge ni tal, he re di tary, and ne o na tal di se a ses and ab nor ma li ti es Ö ÖZ ZE ET T A Am ma aç ç: : Bu ça lış ma da kon je ni tal ano ma li le rin pa to ge ne zi ni ay dın lat ma ya yö ne lik ola rak; ano ma li geli şi min de rol ala bi le cek fak tör ler den an ti ok si dan du rum ve mi ne ral-ağır me tal se vi ye si iliş ki si nin de ğer lendi ril me si amaç lan dı. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Ça lış ma ya çe şit li kon je ni tal ano ma li le ri olan 15 ye ni do ğan ve kon trol gru bu ola rak 15 sağ lık lı ye ni do ğan da hil edil di. Her bir ol gu nun alı nan ve nöz kan ör nek le rin den bir an ti-ok si dan en zim olan erit ro sit katalaz (CAT) ve asit-baz den ge sin de önem li bir rol oy na yan erit ro sit karbonik anhidraz (CA) e...

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“…The detoxification of Cd 21 by a biomolecule has been extensively studied, and most of such studies have adopted the macroscopic method using living organisms in the experiments [9,10,[15][16][17], lacking the information on the detoxification mechanism and interaction nature. Development of a feasible method for the study on the competitive interaction between a pair of antagonists is essential for understanding the antagonism of trace metals in biological systems.…”

Section: Introductionmentioning

confidence: 99%

CE with on‐line detection by ICP‐MS for studying the competitive binding of zinc against cadmium for glutathione

Liu

Jiang

et al. 2008

Electrophoresis

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Development of a feasible method for studying the competitive interaction between a pair of antagonists is essential for understanding the antagonism of trace metals in biological systems. Herein, we report the application of CE on-line coupled with ICP mass spectroscopy (CE-ICP-MS) to investigate the competitive binding of Zn(2+) against Cd(2+) for glutathione (GSH), which is related to the detoxification of Cd(2+) in biological system, and introduce a method to evaluate the kinetics and thermodynamics for the competitive binding of Zn(2+) against Cd(2+) for GSH. The CE-ICP-MS hybrid technique allows easy and sensitive probing of the competitive binding of Zn(2+) against Cd(2+) for GSH and quantitative determination of the important thermodynamic and kinetic parameters of the competitive binding of Zn(2+) against Cd(2+) for GSH. Owing to the high sensitivity and element selectivity with multi-elements detection capacity of ICP-MS, we detailed the evaluation of the kinetics and thermodynamics describing the competition of Zn(2+) against Cd(2+) for GSH from the systematic data obtained by CE-ICP-MS. The competitive binding of Zn(2+) against Cd(2+) for GSH was demonstrated exothermic and thermodynamically favorable (DeltaG = -7.2 kJ/mol) and driven entirely by a large favorable enthalpy decrease (DeltaH = -15.1 kJ/mol) but with an unfavorable entropy decrease (DeltaS = -25.6 J/mol/K). The kinetic data were fit to a second-order equation with the reaction rate constant (k) of (2.18+/-0.10)x10(2) L/(mol x s) under the simulated physiological condition.

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Reduced retention of cadmium in the liver of metallothionein-null mice

Cited by 19 publications

References 7 publications

METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity

METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity

Catalase and Carbonic Anhydrase Enzyme Activities, and Some Mineral-Heavy Metal Concentrations in Newborns with Congenital Malformations

CE with on‐line detection by ICP‐MS for studying the competitive binding of zinc against cadmium for glutathione

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