• 한국환경보건학회지
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• 제21권3호
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• pp.1-15
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• 1995

Tolerance to toxic effects of cadmium(Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats(A, B, C), each consisting of 52 rats, were studied and each group was divided into three subgroups(1,2,3), 28 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 5 days. At the end of the period, rats were challenged with $CdCl_2$(3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after 1,3,5,6 days of pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target-organ of acute Cd 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 short-term exposure to cadmium. This result suggest that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretreatment, served to induce the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

• 한국어병학회지
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• 제14권2호
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• pp.59-64
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• 2001

두툽상어의 간조직 cDNA library의 EST를 통해 중금속의 세포내 농도 조절과 환경으로부터 흡수한 유해 중금속의 해독작용 등의 기능을 수행하는 MT 유전자를 cloning하였다. 염기서열 분석 결과 두툽상어의 MT 유전자는 204bp의 coding 영역과 182bp의 3'UTR 영역으로 구성되어 있었으며, 종결코돈 이후 162bp의 polyadenylatin 신호서열과 이로부터 15bp 이후의 poly(A)서열 등이 확인되었다. 염기서열로부터 유추한 68개의 아미노산 서열에는 다른 척추동물에서와 같이 Cys 잔기가 전체의 29.4%(20/68)로 풍부하였으며, 아미노산 서열수준에서 포유류와는 43~54%, 어류들과는 41~45%의 상동성을 나타냈었다. 특히 20개의 Cys은 어류와 18개가 다른 척추동물과는 19개가 잘 보존되어 있었다. 두툽상어 MT는 특이하게 모든 척추동물에서 잘 보존된 $\beta$-domain 끝 쪽의 9번째 Cys앞에 5개의 아미노산을 더 갖고 있었으며, 경골어류 MT의 특징인 4번째 위치의 gap이 없고, 18번째 Cys의 위치가 어류와 달리 다른 척추동물들과 같았다. 또한 C 말단의 아미노산 잔기가 다른 생물체와는 모두 다른 Ser을 갖는 특징을 나타내었다. 이와 같은 두툽상어 MT유전자의 특징들은 연골어류의 분자적 진화과정을 알 수 있는 분자 표지유전자로 이용할 수 있을 것이다.

• Environmental Analysis Health and Toxicology
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• 제19권2호
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• pp.191-200
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• 2004

Zinc (Zn) is an essential element in biological process, however inadequate Zn status in general population have been recognized. To update the knowledge for Zn-cadmium (Cd) interaction, we studied the intestinal uptake and transport, and the expression of metal transporter proteins (divalent metal transporter 1, DMT1 ; metal transporter protein 1, MTP1 ; zinc transporter 1, ZnTl ; metallothionein 1 , MT1) in duodenum after Cd exposure using Zn deficient animal model. Rats were led Zn deficient (ZnD, 0.5-1.0 mgZn/kg) or Zn supplemented (ZnS, 50mg Zn/kg) diet for 4 weeks, and followed single administration of $^{109}$ CdCl$_2$orally. The body Zn flatus and tissue Cd concentration were determined at 24 hrs after Cd administration. Total body burden of Cd and Cd absorption index (AI, %) were estimated based on the tissue Cd analyzed. DMT1, MTP1, ZnTl and MT1 mRNA were analyzed by using RT-PCR method. Feeding of Zn deficient diet for 4 weeks produced a reduced body weight gain and a depletion of body Zn. Tissue Cd concentration, body burden of Cd and Cd absorption index were higher in the ZnD diet fed rats than the ZnS diet red rats. Especially, Cd concentration in the small intestine (duodenum, jejunum and ileum) and the colon of FeD diet fed rats were higher markedly than in the FeS diet group. The expression levels of DMT1, MTP1 and ZnT1 mRNA in FeD diet fed rats were similar to the FeS diet. The level of MT1 mRNA expression was significantly lower in the FeD than the FeS diet fed rats. Taken together, theses results indicate that Zn deficiency in diet induce an increased intestinal absorption and tissue retention of Cd, and down -regulate the MT1 expression in the intestine which might be play a part of role in Cd absorption and transport in mammalian. These findings suggest that deficiency of essential metal could be enhanced the toxicity of toxic, non-esstial metals through the metal-metal interaction.

• Environmental Analysis Health and Toxicology
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• 제19권4호
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• pp.383-388
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• 2004

In order to elucidate the relationships between cadmium, copper, mercury, zinc levels and metallothionein in the liver and kidney cortex of Korean, the levels of Cd, Zn, Hg, Cu and metallothionein (MT) were determined in the kidney cortex and liver of 50 subjects deceased in the period of January-November, 2001 in the area of Seoul and Gyeonggi Province of Korea. The mean age of the population studied was 36.3+/-12.3 years. The tissues were digested with microwave digestion system and the elements were determined by inductively coupled plasma atomic emission spectrometry. MT was determined by the Cd-hemoglobin affinity assay. The determined levels (mean+/-SD) were: 33.9+/-18.9 micrograms Cd/g wet weight; 47.5+/-12.6 micrograms Zn/g wet weight; 2.5+/-0.57 microgram Cu/g wet weight; 0.26+/-0.31 micrograms Hg/g wet weight, 4.0+/-3.1 mg MT/g wet weight in renal cortex and 2.5+/-1.9 micrograms Cd/g wet weight; 46.9+/-15.0 micrograms Zn/g wet weight; 6.2+/-2.5 micrograms Cu/g wet weight; 0.10+/-0.15 micrograms Hg/g wet weight, 0.92+/-0.57 mg MT/g wet weight in the liver. Positive relationships between Cd and MT, sum of four divalent metal and MT in the kidney cortex were observed. No other correlation was found between Cu and MT, Hg and MT, Zn and MT in either organs.

• 식물조직배양학회지
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• 제28권5호
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• pp.231-237
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• 2001

Differential screening을 통해 Moriguchi등 (1998)이 분리한 유전자와 상동성을 나타내는 CitMT45 유전자의 cDNA를 분리하였다. 본 실험에서 분리한 cDNA는 Moriguchi등 (1998)이 분리한 cDNA에 비해 긴 3' UTR을 가지고 있었다. 잎과 과피, 과육에서 CitMT45 유전자의 발현분석을 northern blot을 통해 수행한 결과, 발달단계에 따라 증가하는 비슷한 앙상을 관찰할 수 있었으나, 과육, 과피, 잎의 순으로 그 발현 양이 많았다. 이들의 발현조절에 대한 정보를 얻기 위해 게놈 DNA를 분리한 결과, CitMT45 게놈 구조는 3개의 exon과 2개의 intron으로 구성되어 있었고, primer extension 분석을 통해 CitMT45 유전자의 발현은 3개의 부위에서 개시되고 있음을 알 수 있었다. 전사개시부위의 5'upstream 지역에서 TATA box와 CCAAT box뿐만 아니라, 금속이온과 온도변화에 의한 조절에 중요한 부위로 알려진 cis-element를 발견하였다.

• 한국수산과학회지
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• 제44권2호
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• pp.126-140
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• 2011

Genetic determinants of two metallothionein isoforms (MT-A and MT-B) were isolated and characterized from the perciform species, rockbream (Oplegnathus fasciatus). Rockbream MT-A and MT-B shared a high degree of homology at amino acid levels with representative orthologs from other perciform species, especially with respect to the conserved cysteine residues. At the genomic level, both MT-A and MT-B genes represent a tripartite structure typical of vertebrate MT genes. However, rockbream MT-B showed unusually large introns (1.2 kb and 0.8 kb for intron I and II, respectively), a phenomenon that has rarely been seen in other vertebrate MT genes. MT-A and MT-B transcripts were ubiquitously detected in a wide array of tissues, wherein brain and eye showed the highest basal expression levels, and the fin exhibited the lowest expression of both isoforms. The basal expression of MT-A in most tissues was significantly higher (ranging from 4- to 10-fold) than that of MT-B. Upon heavy metal exposures to Cd, Cu or Zn at 25 ppb for 48 h, MT-A and MT-B transcripts in the liver were significantly activated by Cd and moderately by Zn. On the other hand, exposure to Cu did not result in alterations of MT-A, nor in the significant suppression of MT-B. Following bacterial challenges with Escherichia coli, Edwardsiella tarda or Streptococcus iniae, MT isoforms in the liver, kidney and spleen were highly modulated and exhibited a pattern that was dependent on the bacterial species, tissues and isoforms. These results suggest that the two MT isoforms could be taken into account as potential indicators of metal toxicity and immune perturbations of this aquaculture-relevant species.

• Journal of Nutrition and Health
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• 제23권6호
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• pp.443-450
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• 1990

임신과 수유 기간 동안 alcohol의 섭취가 어미와 새끼 쥐의 간내 copper 유용에 미치는 영향을 연구하기 위하여 cthanol(0 혹은 30%의 Kcal)과 copper(0.75 혹은 3.75mg/l 식이) 함량에 차이를 둔 식이조성으로 alcohol과 copper의 상호작용을 규명하는 factorial experiment를 수행하였다. 어미 쥐의 열량 섭취와 체중은 식이들에 의해 영향을 받지 않았다. 식이내 copper양이 적을 경우 alcohal을 섭취하지 않은 실험군과 비교하여 alcohol을 섭취한 실험군인 어미 쥐의 간 copper농도가 더욱 감소됨으로써 alcohol과 copper의 상호작용을 보여주었다. 새끼 쥐에게서는 식이내 copper 수준에 관계 없이 어미쥐의 alchol 섭취가 간의 총coppernein의 copper 농도에 반영되었다. Metallothionein의 zinc 함량은 metallothionetin의 copper함량과 반비례적인 관계로 보여주었다. 이상의 결과로 임신과 수유기 동안 식이내 copper함량이 적을 경우 alchol 섭취는 어미와 새끼 모두에게 copper 결핍을 초래할 수 있다는 것을 시사해준다.

• 한국환경보건학회지
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• 제21권3호
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• pp.28-37
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• 1995

This study is performed to find out the effects of selenium against cadmium toxicity. The experimental mice were divided into 6 gruops such as control group, cadmium alone treatment group, selenium treatment groups and two simultaneous treatment groups of selenium and cadmium. Mice were given intraperitoneal administration with two dosage of sodium selenite such as 1.0 mg/kg, 2.5 mg/kg body weight and cadmium chloride was administered 3.0 mg/kg body weight. After giving the challenge dose, the concentration of cadmium and metallothionein and histopathological change of liver and kidney were determined. The results were summarized as follows on 1. The simultaneously administration of selenium and cadmium significantly more decreased cadmium concentration in kidney and iiver tissues compared to the administration of cadmium only(P<0.05). 2. The simultaneously administration of selenium and cadmium more increased metallothionein concentration compared to administration of cadmium only. 3. The simultaneously administration of selenium and cadmium more decreased cadmium concentration in urine compared to the administration of cadmium only. 4. When liver and kidney tissues were observed with optical microscope, no obvious changes were visible in those tissues.

• 환경위생공학
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• 제21권1호
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• pp.52-57
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• 2006

Metallothioneins(MTs) belong to the class of low molecular weight proteins. Recently, it has been suggested that MTs may playa direct role in cellular defense against oxidative stress by functioning as antioxidants. Oxidative damage to different cellular components makes a major contribution to many pathogenenesses. Several studies have demonstrated that MT is able to quench a wide range of reactive oxygen species at a higher efficiency than other well known antioxidants such as superoxide dismutate(SOD). The present study was designed to evaluate the effect of MT on the activities of the reactive oxygen species removal system. MT showed the scavenging of superoxide in the SOD assay system in the presence or absence of SOD. When MT was added to nicotinamide adenine dinucleotide phosphate(NADPH) oxidation system in presence of fixed amount of SOD increase the breakdown rate of superoxide. When MT was added to the system that form nitrite from hydroxylammonium chloride, the formation of nitrite was inhibit. We concluded that the function of MT as antioxidant might have an effect on the level of superoxide scavenging.

• Journal of Nutrition and Health
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• 제29권5호
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• pp.461-471
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• 1996

This study was performed to investigate the effect of dietary protein and cysteine levels on cadmium toxicity in rats. Seventy-two male rats of Sprague-Dawley strain weighting 171$\pm$3g were blocked into 12 groups according to body weight, and were raised for 30 days. cadmium chloride was given at levels of 0 or 400ppm, protein at levels of 7, 15 and 40%, and cysteine was added(total dietary cysteine contents : 0.45%) to diet or not. The results are summarized as follow. Food intake, weight gain, food were lower than those of cadmium free group. But, these were increased with increasing dietary protein level and cysteine addition. Fecal cadmium excretion was remarkably increased in high protein (40%) groups. Thus, cadmium retention rates were decreased in high protein groups. Metallothionein concentrations in liver and kidney were increased in cysteine addition, and cadmium administration. Especially, these were remarkably increased in cadmium and cysteine added groups. Urinary calcium excretion was increased with cadmium administration, but urinary protein excretion and creatinine clearance were not changed in these animal. In conclusion, food intake, weight gain and organ weights were decreased with administration. Cadmium toxicity was alleviated by increasing fecal cadmium excretion, while cysteine addition increased metallothionein concentrations in liver and kidney. From these results, it was shown that cadmium toxicity was alliviated by synergistic effect of high protein level and cysteine addition.