Induction of zinc-thionein in rat liver and kidneys by zinc loading as studied at isometallothionein levels

Suzuki, Kazuto; Yamamura, Masatoshi

doi:10.1016/0378-4274(80)90103-4

Cited by 20 publications

(7 citation statements)

References 12 publications

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“…Firstly, the time course of hepatic zinc uptake after intraperitoneal zinc injection followed a biphasic curve, with an initial zinc uptake between 0 and 12h and a further uptake at 22-36h after injection. Other workers studying hepatic zinc uptake after an intraperitoneal injection of zinc have not reported this phenomenon (Davies et al, 1973;Richards & Cousins, 1975;Suzuki & Yamamura, 1980). However, these earlier studies used time courses which concentrated on the initial 24h after injection.…”

Section: Discussionmentioning

confidence: 99%

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A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection

Cain¹,

Griffiths²

1984

Biochemical Journal

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The time course of hepatic zinc-isometallothionein synthesis was studied in the regenerating liver and compared with that produced after the parenteral injection of zinc (6 mg of Zn2+/kg). In the regenerating liver, zinc levels rose rapidly after partial hepatectomy and reached a maximum at approx. 14h before declining to approximately normal levels at 48h post-operation. During this 48h period most of the zinc was incorporated into metallothionein. Purification of the latter into the charge-separable isometallothioneins (i.e. MT1 and MT2) showed that, in the regenerating liver, there was an unequal distribution of zinc between the two isoproteins. Thus at operation the endogenous thionein had an MT2/MT1 ratio of 1; after regeneration this ratio increased, and all times during the time course there was more MT2 than MT1. In contrast, the intraperitoneal injection of zinc produced a biphasic uptake of zinc into the liver with maxima at 10h and 32h. During the first phase of zinc uptake, metallothionein synthesis increased rapidly and, unlike the regenerating liver, the MT2/MT1 ratio of 1 remained constant. Thereafter, this ratio increased in a manner analogous to that exhibited by the regenerating liver. Half-life determinations for thionein disappearance/degradation shows that MT2 and MT1 were degraded with half-lives (t1/2) of 26.18h and 16.44h respectively in the regenerating liver and 14.75h and 9.3h after zinc injection. Thus thionein disappearance/degradation in the regenerating liver was slower than that seen after zinc injection. However, in both situations MT2 was always removed at a slower rate than MT1. Calculation of the rates of thionein synthesis (assuming the above disappearance rates were constant throughout the time course) showed that, in the regenerating liver, the rate of MT2 synthesis was approximately twice that of MT1. This was not the case after zinc injection, where both isometallothioneins were synthesized in equal amounts. These results demonstrate that the rates of synthesis of MT2 and MT1 can be altered according to the metabolic status of the cell and suggest a specific role for MT2 during liver regeneration.

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Section: Discussionmentioning

confidence: 99%

“…However, these earlier studies used time courses which concentrated on the initial 24h after injection. Thereafter, the time points were usually placed at 24h intervals (see, e.g., Suzuki & Yamamura, 1980). If similar time points were used in the present study (Fig.…”

Section: Discussionmentioning

confidence: 99%

A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection

Cain¹,

Griffiths²

1984

Biochemical Journal

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“…Interestingly, one vertebrate species, the chicken, appears to possess only one form of MT, which is similar in ionic characteristics to the major mammalian isoform I (16-18). Studies of the significance of MT polymorphism (19)(20)(21)(22) in mammals have not established functional differences between isoforms.In contrast to the extensive reports on the primary structure of MTs from mammalian species (23) and of organisms such as fungi (7), yeast (6,24), crab (15), and sea urchin (4), there is little or no direct information concerning the primary structure of MTs from nonmammalian vertebrates. A partial sequence of plaice MT has been reported (25) but the complete primary structure has not been determined.…”

mentioning

confidence: 99%

“…Interestingly, one vertebrate species, the chicken, appears to possess only one form of MT, which is similar in ionic characteristics to the major mammalian isoform I (16)(17)(18). Studies of the significance of MT polymorphism (19)(20)(21)(22) in mammals have not established functional differences between isoforms.…”

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confidence: 99%

Amino acid sequence and comparative antigenicity of chicken metallothionein.

McCormick

Fullmer

Garvey

1988

Proc. Natl. Acad. Sci. U.S.A.

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The complete amino acid sequence of metallothionein (MT) from chicken liver is reported. The primary structure was determined by automated sequence analysis of peptides produced by limited acid hydrolysis and by trypsin digestion. The comparative antigenicity of chicken MT was determined by radioimmunoassay using rabbit anti-rat MT polyclonal antibody. Chicken MT consists of 63 amino acids as compared to 61 found in MTs from mammals. One insertion (and two substitutions) occurs in the amino-terminal region, a region considered invariant among mammalian MTs. Eighteen of the 20 cysteines in chicken MT were aligned with cysteines from other mammalian sequences. Two cysteines near the carboxyl terminus are shifted by one residue due to the insertion of proline in that region. Overall, the chicken protein showed =68% sequence identity in a comparison with various mammalian MTs. The affinity of the polyclonal antibody for chicken MT was decreased by 2 orders of magnitude in comparison to that of a mammalian MT (rat MT isoforms). This reduced affinity is attributed to major substitutions in chicken MT in the regions of the principal determinants of mammalian MTs. Theoretical analysis ofthe primary structure predicted the secondary structure to consist of reverse turns and random coils with no stable I8 or helix conformations. There is no evidence that chicken MT differs functionally from mammalian MTs.Isolated and characterized some 30 years ago (1, 2), the cysteine-rich, metal-binding protein metallothionein (MT) is now recognized to exist in several tissues of virtually every vertebrate species examined (3). However, despite extensive characterization of MT, the precise biological function is not known. Similar cysteine-rich proteins have also been found in invertebrates such as sea urchin (4) and crab (5) and in microorganisms such as yeast (6) and fungi (7), suggesting that MTs are ubiquitous.Mammalian MTs contain 30% cysteine and have no leucine, histidine, or aromatic amino acids and generally only one amino-terminal methionine. Typically, four amino acids (cysteine, seine, lysine, and alanine) can account for 70o of the residues in MT. Most mammalian MTs studied so far contain 61 amino acids, which are aligned in a highly conserved primary structure. In fact, the positions of the 20 cysteines in the sequences of all MTs from vertebrates studied so far are invariant (3), undoubtedly reflecting the importance of these residues in the coordination of metals (8, 9). Other regions of the sequence are also invariant, but the functional significance of these remains to be determined. One invariant region at the amino terminus (residues 1-5) and one homologous region (residues 20-26) have been shown to be the primary antigenic determinants for mammalian MTs (10). Presently, there are no data concerning the principal determinants for nonmammalian MTs.MTs of many species exhibit polymorphism. Two major isoforms of MT exist in tissues from a wide variety of species ranging from humans to crabs (11-15). Interesting...

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“…For example, MT-1 was reported to be predominantly synthesized in the livers of mice after Zn injections or in those of tumor-bearing mice, 36) and in the liver of rats, MT-2 levels also increased, rather than MT-1 levels, after Zn treatment. 37,38) On the contrary, induction of MT-2 was reportedly greater than that of MT-1 in the liver of Zn-treated mice or tumor cells, 39) and Cu containing MT-2 induction was enhanced to a greater extent than that of MT-1 in the liver of LEC rats with the development of hepatitis. 24) In addition, commercially available MT-1 and MT-2 standards were observed to contain sub-isoforms.…”

Section: Diagnostic Analysis Of Human and Lec Rat Hepaticmentioning

confidence: 91%

An Improved Diagnostic Method for Chronic Hepatic Disorder: Analyses of Metallothionein Isoforms and Trace Metals in the Liver of Patients with Hepatocellular Carcinoma as Determined by Capillary Zone Electrophoresis and Inductively Coupled Plasma-Mass Spectrometry

Kawata

Nakamura

Nakayama

et al. 2006

Biological & Pharmaceutical Bulletin

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Metallothionein (MT) is a low molecular weight and cysteine-rich protein that binds to several heavy metals. The suggested functions of MT are detoxification of heavy metals, maintenance of trace element homeostasis, and scavenging of free radicals via the thiol groups present in the protein.1,2) Hepatocellular carcinoma (HCC) is one of the most common human tumors that occurs globally, and generally develops from chronic hepatitis (CH) and liver cirrhosis (LC). [3][4][5] It is, therefore, very important to detect and evaluate the progressing state of chronic hepatic disorder in order to diagnose the diseases.We have previously reported that abnormal accumulations of both copper (Cu) and total MT occur in the livers of Long Evans Cinnamon (LEC) rats and that these accumulations are directly related to the development of jaundice and hepatoma.6-10) Similar observations have been reported with regard to the livers of HCC patients, although the concentrations of metals and total MT accumulations differed among the studies. [11][12][13][14] Many researchers have reported that the serum copper/zinc (Cu/Zn) ratio is sufficiently sensitive to diagnose various diseases. [15][16][17] The serum Cu/Zn ratio in the patients with different hepatic diseases has been confirmed to be significantly higher than that of patients without hepatic disorders (Ctrl). [18][19][20] However, during our study, some patients with congestive heart failure, diabetes mellitus, and hypertension exhibited markedly high Cu/Zn ratio, indicating that the ratio could not be considered selective for diagnosing the diseases. On the other hand, we also reported that Cu concentrations in the human liver cytosol increased with the development of HCC. [18][19][20] The increase in Cu concentrations in the hepatic tissues were due to the distribution of Cu in MT rather than in superoxide dismutase (SOD) in the hepatic tissues.21) Based on these observations, we attempted to determine whether monitoring of MT isomers and metal concentrations in human liver is a better approach for diagnosing human liver disorder.It is well known that MT occurs in several isoforms, 22) among which MT-1 and MT-2 are induced in most organs by specific stimuli such as exposure to toxic metals and glucocorticoids. 23) Although the biological functions and physiological role of MT are not yet known, based on the results of the analysis of hepatic MT-1 and MT-2 in LEC rats we recently proposed that MT-1 is related to the metabolism or detoxification of toxic metals such as cadmium, and, MT-2 is responsible for the homeostasis of essential metals such as Cu.24) Since the pathophysiological feature of hepatic disorders in LEC rats has been reported to be very similar to that of human hepatic diseases involving HCC, 25,26) we attempted to determine MT-1 and MT-2 in the liver cytosol of humans by using a capillary zone electrophoresis (CZE). Previously, It is desirable to diagnose hepatocellular carcinoma (HCC) in the early stages during its development since its treatment is usually d...

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Induction of zinc-thionein in rat liver and kidneys by zinc loading as studied at isometallothionein levels

Cited by 20 publications

References 12 publications

A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection

A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection

Amino acid sequence and comparative antigenicity of chicken metallothionein.

An Improved Diagnostic Method for Chronic Hepatic Disorder: Analyses of Metallothionein Isoforms and Trace Metals in the Liver of Patients with Hepatocellular Carcinoma as Determined by Capillary Zone Electrophoresis and Inductively Coupled Plasma-Mass Spectrometry

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