Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

Mh, Vasconcelos; Tam, Siu-Cheung; Beattie, JH; Je, Hesketh

doi:10.1042/bj3150665

Cited by 53 publications

(29 citation statements)

References 35 publications

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“…As previously reported Cherian, 1981, 1982;Vasconcelos et al, 1996;Iszard et al, 1995;Eaton et al, 1980;Klaassen and Liu, 1998;Kotsonis and Klaassen, 1978;Schnell et al, 1978), the increase of the MT level was very high in the liver, however, our results showed that MT induction occurred with lower doses of Cd than those used in the literature and these did not lead to the significant toxicity demonstrated by clinical signs. This increase of the hepatic MT level appeared from 12 h which is in accordance with the rapid (5 h) increase of hepatic MT mRNA reported by Vasconcelos et al (1996), and was maintained or was even higher until 72 h. This has not been described in the literature. The highest response of the liver compared with the kidney has been described with higher doses of Cd, i.e.…”

Section: Discussionsupporting

confidence: 44%

“…This increase in the concentration of MT can be considered as induced synthesis of MT in these tissues because an intracellular protein such as MT is not transferred from one organ to another during the short experimental period of the study (Onosaka and Cherian, 1982). As previously reported Cherian, 1981, 1982;Vasconcelos et al, 1996;Iszard et al, 1995;Eaton et al, 1980;Klaassen and Liu, 1998;Kotsonis and Klaassen, 1978;Schnell et al, 1978), the increase of the MT level was very high in the liver, however, our results showed that MT induction occurred with lower doses of Cd than those used in the literature and these did not lead to the significant toxicity demonstrated by clinical signs. This increase of the hepatic MT level appeared from 12 h which is in accordance with the rapid (5 h) increase of hepatic MT mRNA reported by Vasconcelos et al (1996), and was maintained or was even higher until 72 h. This has not been described in the literature.…”

Section: Discussionmentioning

confidence: 72%

“…It has been shown that MT is efficiently induced in many human and animal organs, particularly in liver tissue, in response to heavy metals such as Zn or Cd (Piscator, 1964;Norberg, 1979;Kagi and Kojima, 1987) and agents which cause oxidative stress such as starvation (Kagi 1991), heat (Lazo et al, 1995), restraint (Hidalgo et al, 1988), Zn-or Cu-deficient diets and inflammation (Kagi and Shaffer, 1988;Brady, 1991). The effect of cadmium, one of the inducers most used, has been investigated widely (Onosaka and Cherian, 1981;Vasconcelos et al, 1996;Kenaga et al, 1996;Iszard et al, 1995;Eaton et al, 1980;Klaassen and Liu, 1998;Minami et al, 1996). Even though the induction of MT has been demonstrated in adult rat liver after injection of high amounts of Cd, little is known about MT induction in other tissues.…”

Section: Introductionmentioning

confidence: 98%

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Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

Bobillier-Chaumont¹,

Maupoil²,

Berthelot³

2005

J. Appl. Toxicol.

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Metallothionein (MT), induced in different organs in response to heavy metals and oxidative conditions, exerts antioxidant properties and thus could be implicated in cardiovascular physiopathology. The aim of this study was to investigate the capacity of cadmium (Cd) and isoproterenol to induce in vivo MT not only in rat liver and kidneys but also in heart and aorta. Tissue MT levels, catalase (CAT) and glutathione peroxidase (GPX) activities were assayed at different times after Cd or isoproterenol injection. Cd induced a dose-dependent induction of MT with a higher response in the liver than in the kidney, aorta and heart. The hepatic increase was early (12 h) and maintained (72 h), whereas the elevation was maximal around 48 h for the other organs. Isoproterenol induced a transient (12 h) hepatic and a biphasic (12 and 36 h) renal and cardiac increase. CAT activity was decreased in the liver and increased in the heart with the higher Cd doses. Isoproterenol increased the cardiac GPX activity. In conclusion, the results demonstrate that MT can be induced in rat liver and kidneys but also in heart after a Cd or isoproterenol injection. This enhancement of cardiac and vascular MT levels could be used to study the potential protective effect of MT in cardiovascular diseases.

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Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 98%

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Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

Bobillier-Chaumont¹,

Maupoil²,

Berthelot³

2005

J. Appl. Toxicol.

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“…While there is evidence of transcriptional control of MT expression at gene level, there is only little evidence of post-transcriptional regulation of MT synthesis (Vasconcelos et al, 1996). The mechanism of translational control of MT synthesis is still unknown, but, probably, it may require the participation of specific protein factors interacting with MT mRNA.…”

Section: Discussionmentioning

confidence: 99%

Metallothionein in Antarctic notothenioids: Genetic polymorphism and differential gene expression

Carginale

Scudiero

Capasso

et al. 2000

Italian Journal of Zoology

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Among Antarctic notothenioids, appreciable amounts of hepatic metallothionein were found in red-blooded species, whilst very little metallothionein, if any, was detected in icefish. In contrast, high levels of metallothionein mRNA were revealed in both fishes by Northern blot analysis of total RNA. Phylogenetic analyses carried out on the metallothionein sequences obtained by using reverse-transcriptase polymerase chain reaction on eight notothenioid species revealed that notothenioid metallothioneins can be divided into two groups, metallothionein-I and metallothionein-II, indicating that they arose from at least one gene duplication event occurring in the ancestral lineage of the Notothenioidei. A strong induction of metallothionein gene expression and metallothionein accumulation could be obtained in icefish injected with cadmium salt. Apparently, the expression of the genes encoding MT-I and MT-II in icefish liver is differentially regulated by cadmium. The discrepancy between metallothionein mRNA levels and amounts of metallothionein protein observed in icefish was observed also in red-blooded species. In Notothenia coriiceps, the profile of metallothionein mRNA accumulation, as well as that of the metallothionein levels, differs substantially in different tissues suggesting the presence of an organ-specific regulation of metallothionein genes.

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“…However, regulation at the translational level whether synthesis or degradation of MT should be considered. Vasconcelos et al [2002], have shown that the levels in liver and testes can also be markedly different through this mechanism [Vasconcelos et al 1996] perhaps rendering the testes more susceptible to Cd toxicity than liver.…”

Section: Resultsmentioning

confidence: 99%

Expression of Metallothionein-1 (MT-1) mRNA in the Rat Testes and Liver After Cadmium Injection

Mukhopadhyay

Mitra

Nandi

et al. 2009

Systems Biology in Reproductive Medicine

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Metallothioneins (MTs) belong to the family of stress proteins that are present in the majority of living organisms. The MTs play an important task in detoxifying heavy metals. The mammalian scrotal testis is known to be susceptible to cadmium (Cd) exposure. The present work focuses on the MT-1 isoform and aims to ascertain and confirm previous findings to answer whether rodent testes indeed contain MT-1 mRNA, whether its level is increased with Cd injection in liver and testes, and lastly what is the relative difference in the expression of MT-1 mRNA in liver and testes both with and without Cd injection. Adult male Wistar rats weighing 270-290 g received a subcutaneous injection of 4.0 mmol Cd/kg and were sacrificed by cervical dislocation 6 h later. RNA was isolated from testes as well as the liver. There were 2 replicates per treatment for RNA analyses. MT-1 mRNA levels were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis and then assessed by densitometry scanning. The results of RT-PCR clearly demonstrated that the rodent testes express MT-1 mRNA. The densitometry data shows that the expression of MT-1 mRNA increases with Cd treatment in testes. The relative level of MT1-mRNA is greater in the control-liver than in the control-testes. However, upon Cd injection, the level of testes MT-1 mRNA increases 2.16 fold. These results suggest that the testes respond to Cd for at least 6 h post injection through a transcriptional mechanism.

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Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

Cited by 53 publications

References 35 publications

Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

Metallothionein in Antarctic notothenioids: Genetic polymorphism and differential gene expression

Expression of Metallothionein-1 (MT-1) mRNA in the Rat Testes and Liver After Cadmium Injection

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