Arsenic induces and enhances rat hepatic metallothionein production in vivo

Albores, Arnulfo; Koropatnick, James; Cherian, M. George; Żelazowski, Andrzej J.

doi:10.1016/0009-2797(92)90057-r

Cited by 75 publications

(46 citation statements)

References 24 publications

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“…Fisrt, inducation of Ar was found in rat hepatic metallothionein in vivo (Albores et al, 1992). Complex interactions also were found between Ar and human metallothionein (Toyama et al, 2002;Ngu and Stillman, 2006).…”

Section: Other Heavy Metals and Arsenic (Ar)mentioning

confidence: 83%

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

Weichao

Mao

et al. 2014

Front. Mar. Sci.

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The documents on Metallothioneins (MTs) in aquatic creatures, especially focusing on their function as biomarkers in environmental monitoring programmes, are vast and increasing. There are, however, few papers to summary the physiological role of MTs in aquatic organisms especially on development. The multifaceted roles of MTs include involvement in homeostasis, protection against heavy metals and oxidant damages, and metabolic regulation, sequestration and/or redox control. In this paper, we have collected published information on MTs in aquatic organisms-pisces, amphibians, mammals, etc., and analyzed their function in these aquatic animals. MTs have four main functions in aquatic vertebrate. They are respectively bioaccumulation of toxic metals and detoxification, homeostatic regulation of metals, protection against oxidative stress and neuroprotective mechanism. MTs separate in different tissues and they have various distributions in different tissues of aquatic vertebrate, including liver, gills, kidney, testes, and brain. MTs can be induced by a variety of environmental and physiological factors, among which, heavy metals are the main kind of MTs inducers in aquatic vertebrate. Here we pay more attention on the essential metals copper (Cu) and zinc (Zn) and the non-essential metals cadmium (Cd), silver (Ag), lead (Pb), and mercury (Hg).

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Section: Other Heavy Metals and Arsenic (Ar)mentioning

confidence: 83%

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

Weichao

Mao

et al. 2014

Front. Mar. Sci.

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“…In addition to potent MT-inducing metals such as zinc, cadmium, copper, mercury, silver, and bismuth, other metals such as chromium, iron, cobalt, nickel, arsenic, and manganese can also induce MT but to the lesser levels (Fleet et al, 1990;Albores et al, 1992). These weak MT-inducing metals…”

Section: Introductionmentioning

confidence: 99%

“…It is generally perceived that the expression of the MT gene in response to a metal load is regulated by metal-responsive transcription factor 1 (MTF-1) that binds to the metal-response elements of the promoter region of MT genes (Heuchel et al, 1994). The mechanisms underlying the activation of the MT gene through the interaction of MTF-1 and metal-response elements have been investigated extensively (Andrews, 2001;Otsuka, 2004), but the precise mechanism of MT induction by nonzinc metals, including cadmium has been poorly understood (Daniels et al, 2002;Wang et al, 2004).In addition to potent MT-inducing metals such as zinc, cadmium, copper, mercury, silver, and bismuth, other metals such as chromium, iron, cobalt, nickel, arsenic, and manganese can also induce MT but to the lesser levels (Fleet et al, 1990;Albores et al, 1992). These weak MT-inducing metals…”

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confidence: 99%

Induction of Metallothionein by Manganese Is Completely Dependent on Interleukin-6 Production

Kobayashi¹,

Kuroda²,

Shibata³

et al. 2006

J Pharmacol Exp Ther

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Metallothionein (MT) is a cysteine-rich protein that binds to and is inducible by heavy metals such as cadmium and zinc. However, the precise mechanism of MT induction by other metals remains unclear. In the present study, we investigated the mechanism of MT induction by manganese, focusing on the involvement of cytokine production. Administration of MnCl 2 to mice resulted in the induction of MT dose-dependently in the liver with little accumulation of manganese. Speciation analysis of metals in the liver cytosol showed that the major metal bound to the induced MT was zinc. Administration of MnCl 2 caused an increase in mRNA levels of interleukin-6 (IL-6) in the liver as well as an increase in serum levels of IL-6 but not those of other inflammatory cytokines. Subsequently, serum levels of serum amyloid A (SAA), an acute-phase protein induced by IL-6, increased with a peak at 24 h. However, no increase in serum alanine aminotransferase activity was observed, suggesting that manganese enhanced the production of IL-6 and SAA without causing liver injury. In response to IL-6, the expression of a zinc transporter, ZIP14, was enhanced in the liver, possibly contributing to the synthesis of hepatic zinc-MT. In IL-6-null mice, the induction of hepatic MT by treatment with MnCl 2 was completely suppressed to the control level. These results suggest that manganese is a unique metal that induces the synthesis of hepatic MT completely depending on the production of IL-6 without accompanying liver injury.Metallothionein (MT) is a cysteine-rich low-molecularweight protein with a high affinity for heavy metals. Physiological roles of MT encompass a broad spectrum, including detoxification of heavy metals, scavenging of free radicals, regulation of cell growth, and maintenance of homeostasis of trace metals such as zinc and copper (Suzuki et al., 1993). The most prominent characteristic of MT is its inducibility not only by metals but also by various factors such as hormones, cytokines, organic chemicals, starvation, and physical stress (Kä gi, 1993). It is generally perceived that the expression of the MT gene in response to a metal load is regulated by metal-responsive transcription factor 1 (MTF-1) that binds to the metal-response elements of the promoter region of MT genes (Heuchel et al., 1994). The mechanisms underlying the activation of the MT gene through the interaction of MTF-1 and metal-response elements have been investigated extensively (Andrews, 2001;Otsuka, 2004), but the precise mechanism of MT induction by nonzinc metals, including cadmium has been poorly understood (Daniels et al., 2002;Wang et al., 2004).In addition to potent MT-inducing metals such as zinc, cadmium, copper, mercury, silver, and bismuth, other metals such as chromium, iron, cobalt, nickel, arsenic, and manganese can also induce MT but to the lesser levels (Fleet et al., 1990;Albores et al., 1992). These weak MT-inducing metals

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“…Arsenicals, including DMAA, are moderately effective inducers of MT in mice and rats [8,9] . MTs, thiol-rich metal binding proteins, have been shown to be easily induced by oxidative stress and heavy metals and play an important role in homeostasis of essential metals, detoxication of heavy metals, scavenging reactive oxygen intermediates and preventing carcinogenesis as an endogenous defensive factor [10][11][12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Protective role of metallothionein (I/II) against pathological damage and apoptosis induced by dimethylarsinic acid

Chen¹,

Gu²,

Chen³

et al. 2003

WJG

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AIM:To better clarify the main target organs of dimethylarsinic acid toxicity and the role of metallothionein (MTs) in modifying dimethylarsinic acid (DMAA) toxicity. METHODS:MT-I/II null (MT -/-) mice and the corresponding wild-type mice (MT +/+ ), six in each group, were exposed to DMAA (0-750 mg/kg body weight) by a single oral injection. Twenty four hours later, the lungs, livers and kidneys were collected and undergone pathological analysis, induction of apoptotic cells as determined by TUNEL and MT concentration was detected by radio-immunoassay. RESULTS:Remarkable pathological lesions were observed at the doses ranging from 350 to 750 mg/kg body weight in the lungs, livers and kidneys and MT +/+ mice exhibited a relatively slight destruction when compared with that in dose matched MT -/-mice. The number of apoptotic cells was increased in a dose dependent manner in the lungs and livers in both types of mice. DMAA produced more necrotic cells rather than apoptotic cells at the highest dose of 750 mg/kg, however, no significant increase was observed in the kidney. Hepatic MT level in MT +/+ mice was significantly increased by DMAA in a dose-dependent manner and there was no detectable amount of hepatic MT in untreated MT -/-mice. CONCLUSION:DMAA treatment can lead to the induction of apoptosis and pathological damage in both types of mice. MT exhibits a protective effect against DMAA toxicity.

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Arsenic induces and enhances rat hepatic metallothionein production in vivo

Cited by 75 publications

References 24 publications

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

Induction of Metallothionein by Manganese Is Completely Dependent on Interleukin-6 Production

Protective role of metallothionein (I/II) against pathological damage and apoptosis induced by dimethylarsinic acid

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