• Title/Summary/Keyword: metallothionein(MT)

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Metallothionein Induction and Its Protective Effect in Liver and Kidney of Rats Exposed to Cadmium Chloride (Cadmium에 의한 흰쥐의 간장 및 신장의 Metallothionein 변화와 방어효과)

  • Kim, Nam-Song;Lee, Jae-Hyung;Koh, Dai-Ha;Ki, No-Suk;Hwang, In-Dam
    • Journal of Preventive Medicine and Public Health
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    • v.24 no.3 s.35
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    • pp.287-304
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    • 1991
  • Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), $CdCl_2$ (0.5 mg/kg, B), and $ZnCl_2$ (13.0 mg/kg, C) during time periods of $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

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Metallothioneins and Oxidative Stress

  • Beattie, John H.;Trayhurn, Paul
    • Nutritional Sciences
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    • v.5 no.4
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    • pp.228-233
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    • 2002
  • The low molecular weight zinc-binding protein metallothionein(MT) contains 32% cysteine and has been shown to efficiently scavenge hydroxyl radicals in vitro. MT expression is induced by oxidative stress and an antioxidant role for this protein has therefore been proposed. This review mainly focuses on the evidence for this role arising from studies using genetically modified animals and cells which either over- or under-express MT. Despite some considerable disparity of results in the literature, reported studies do generally support an antioxidant role. Nevertheless, oxidant stress at non-physiological treatment levels has been the preferred experimental model and there is little information about the role of MT in physiological oxidative stress. Although it is presumed that the mechanism by which MT has an antioxidant effect involves oxidation of cysteinal thiols, it is possible that zinc release from MT is in itself an important signalling factor.

Metallothioneins and Oxidative Stress

  • Beattie, John H.;Trayhurn, Paul
    • Proceedings of the Korean Nutrition Society Conference
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    • 2002.11b
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    • pp.1171-1177
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    • 2002
  • The low molecular weight zinc-binding protein metallothionein (MT) contains 32% cysteine and has been shown to efficiently scavenge hydroxyl radicals in vitro. MT expression is induced by oxidative stress and an antioxidant role for this protein has therefore been proposed. This review mainly focuses on the evidence for this role arising from studies using genetically modified animals and cells which either over-or under-express MT. Despite some considerable disparity of results in the literature, reported studies do generally support an antioxidant role. Nevertheless, oxidant stress at non-physiological treatment levels has been the preferred experimental model and there is little information about the role of MT in physiological oxidative stress Although it is presumed that the mechanism by which MT has an antioxidant effect involves oxidation of cysteinal thiols, it is possible that zinc release from MT is in itself an important signalling factor.

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Phylogenetic Analysis based on Metallothionein Gene Sequence of an Indigenous Species Pisidium (Neopisidium) coreanum in Korea (한국 고유종 Pisidium (Neopisidium) coreanum (산골조개) 의 metallothionein 유전자를 기초로 한 분자계통 분류학적 연구)

  • Baek, Moon-Ki;Lee, Jun-Seo;Kang, Se-Won;Lee, Jae-Bong;Kang, Hyun-Jung;Jo, Yong-Hun;Noh, Mi-Young;Han, Yeon-Soo;Choi, Sang-Haeng;Chae, Sung-Hwa;Park, Hong-Seog;Lee, Jun-Sang;Lee, Yong-Seok
    • The Korean Journal of Malacology
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    • v.25 no.2
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    • pp.153-160
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    • 2009
  • Pisidium (Neopisidium) coreanum is a freshwater snail and lives in spring water near mountain areas. Interestingly, this snail has been traditionally regarded as medicinal food, and thus has been used as folk remedies for healing broken bones. Recently, alpha classification on Pisidium (Neopisidium) coreanum through redescription has been conducted. However, not much attention has been made in beta classification. In this study, we performed the beta classification based on metallothionein (MT) genes found from various organisms. To this end, the complete cDNA sequences were obtained from the Expressed Sequence Tag (EST) sequencing project of Pisidium (Neopisidium) coreanum. The coding region (315 bp) encoded an amino acid sequence of 105 residues. The combined results from BLAST analyses, multiple sequence alignment and molecular phylogenetic study of Pc-MT gene indicate that Pisidium (Neopisidium) coreanum has similarity to freshwater bivalve such as Dreissena polymorpha (zebra mussel), Unio tumidus (swollen river mussel) and Crassostrea ariakensis (suminoe oyster).

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Metallothioneins and oxidative stress

  • Beattie, John H.;Trayhurn, Paul
    • Proceedings of the Korean Nutrition Society Conference
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    • 2002.11a
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    • pp.73-82
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    • 2002
  • The low molecular weight zinc-binding protein metallothionein (U) contains 32% cysteine and has been shown to efficiently scavenge hydroxyl radicals in vitro. MT expression is induced by oxidative stress and an antioxidant role for this protein has therefore been proposed. This review mainly focuses on the evidence for this role arising from studies using genetically modified animals and cells which either over- or under-express MT. Despite some considerable disparity of results in the literature, reported studies do generally support an antioxidant role. Nevertheless, oxidant stress at non-physiological treatment levels has been the preferred experimental model and there is little information about the role of MT in physiological oxidative stress. Although it is presumed that the mechanism by which MT has an antioxidant effect involves oxidation of cysteinal thiols, it is possible that zinc release from MT is in itself an important signalling factor.

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Bioaccumulation of Heavy Metals in Intestine of Nacella concinna (남극삿갓조개 (Nacella concinna) 장의 중금속 축적에 관한 연구)

  • Lee, Yong-Seok;Jo, Yong-Hun;Han, Yeon-Soo;Kho, Weon-Gyu;Ahn, In-Young;Jeong, Kye-Heon
    • The Korean Journal of Malacology
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    • v.22 no.1 s.35
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    • pp.87-95
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    • 2006
  • Immunohistochemical and ultrastuructural experiments were conducted to find out heavy metal accumulation in the intestine of an Antarctic gastropod Nacella concinna. According to the immune-histochemical experiment the apical cytoplasm of the intestinal epithelium showed positive reactions to anti-MT (rnotallothionein), indicating the presence of MT, a metal-binding protein involved in metal detoxifying process. In the transmission electron microscopic observations, the epithelial cells of the intestine exposed to Cd for over three hours showed irregular nuclear membranes, secretory granules, and probable metal granules. According to the SEM-EDS experiments on the intestine, concentration of Pb in the apical epithelium was in inverse proportion to that in the intestinal lumen. After exposing to Cd for over three days, S was rapidly reduced. Ca and Zn were rapidly increased after exposure to Cd. These elements are supposed to be concerned with the MT-reaction in the intestine. laken together, these data suggest that N. concinna could be used as a potential biomarker species.

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Microarray Analysis of the Gene Expression Profile in Diethylnitrosamine-induced Liver Tumors in Mice

  • Jung Eun-Soo;Park Jung-Duck;Ryu Doug-Young
    • Environmental Mutagens and Carcinogens
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    • v.25 no.4
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    • pp.134-142
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    • 2005
  • Liver cancer is a leading cause of tumor-related mortality, Diethylnitrosamine (DEN) is one of the most extensively studied hepatic carcinogens to date. In this study, the mRNA expression profile in DEN-induced liver tumors in mice was analyzed using DNA microarrays. We report increased expression of genes that participate in hypoxia response, including metallothionein 1 (Mt1), metallothionein 2 (Mt2), fatty acid synthase (Fasn), transferrin (Trf), adipose differentiation-related Protein (AdfP) and ceruloplasmin (CP), as well as those involved in predisposition and development of cancers, such as cytochrome P450 2A5 (Cyp2a5), alpha 2-HS-glycoprotein (Ahsg) and Jun-B oncogene (Junb). The hepatic iron regulatory peptide, hepcidin (Hampl), was downregulated in DEN-stimulated liver tumors. Expression of tumor suppressor genes, such as tripartite motif protein 13 (Trim13), was decreased under these conditions. The data collectively indicate that DEN-induced tumor development can be exploited as a possible model for liver cancer, since this process involves various genes with important functions in hepatic carcinogenesis.

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Effects of Chitosanoligosaccharide on the Mouse Hepatotoxicity Induced by Cadmium (카드뮴으로 유발된 생쥐 간독성에 대한 키토산올리고당의 효과)

  • Yoon, Jung-Sik;Roh, Young-Bok
    • Applied Microscopy
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    • v.32 no.4
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    • pp.361-376
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    • 2002
  • This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the other group was injected with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, cadmium concentration in liver tissues and metallothionein (MT) concentration were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. Cadmium concentration in liver tissues was drastically lower in groups Cd+Chi than in group Cd. MT concentration in liver tissues was lower in group Cd than in groups Cd+Chi. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi, mitochondria with high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.

Preventive Effects of Zinc Pretreatment in the Time-course of Cadmium-induced Testicular Toxicity in the Rat (아연 전처리가 시간 경과에 따른 카드뮴 유도 고환 독성에 미치는 보호 효과)

  • Jekal, Seung-Joo;Lee, Kyung-Sun;Chung, Ok-Bong;Im, Hyo-Bin
    • Korean Journal of Clinical Laboratory Science
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    • v.41 no.3
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    • pp.111-122
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    • 2009
  • Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to investigate the morphological effects and metallothionein (MT) expression by zinc pretreatment in the course of time of cadmium-induced testicular injury in rat. Fifty male Spraque-Dawley rats weighing 160~180 g were divided into two groups : saline-pretreated cadmium group and zinc-pretreated cadmium group. Rats of two groups received subcutaneous injection of saline and 100 mg/kg $ZnSO_4$ at 0, 2, 5 and 8 hrs intervals respectively. Cadmium chloride (4.5 mg/kg $CdCl_2$) was administrated intraperitoneally at 2 hrs after zinc injection and rats were killed 0, 12, 24, 48 and 72 hrs later. Testicular tissue damages, interstitial (Leydig) cells status and MT expression were determined using hematoxylin-eosin stained sections and a computerized image analysis system on sections immunostained with a mouse anti-metallothionein respectively. Zinc pretreatment was significantly reduced testicular damages in five pathological categories after cadmium administation. The number of surviving interstitial cells was significantly higher in the zinc-pretreated group than in the saline-preatreated group at 48 and 72 hrs after cadmium administration. Non-damaged testis showed the positivity of MT staining in spermatogenic cells, Sertoli cells and endothelium of blood vessel, but not in the Leydig cells. The positivity of MT staining in saline-pretreated group was significantly reduced at 24 hrs after cadmium administration, whereas zinc-pretreated group showed strong MT positive staining similar to the 0 hr by 42 hrs after cadmium administration. In damaged testis, MT positive staining was also observed in the Leydig cells of both groups. These results suggest that a major preventive effect of zinc against cadmium-induced testicular toxicity may be due to its ability to reduce the cytotoxicity of cadmium in spermatogenic cells and Leydig cells by inhibiting the susceptibility of the testis to cadmium but not MT production by cadmium.

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