Localization of metallothionein in nuclei of growing primary cultured adult rat hepatocytes

Tsujikawa, Kazutake; Imai, Takumi; Kakutani, Makoto; Kayamori, Yuzo; Matsui, Tsutomu; Otaki, Noriko; Kimura, Masami; Fukuyama, Ryuichi; Shimizu, Nobuyoshi

doi:10.1016/0014-5793(91)80597-v

Cited by 116 publications

(65 citation statements)

References 10 publications

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“…In cultured adult rat hepatocytes, metallothionein accumulates in nuclei at early S-phase, but not at Go or G1 when the protein is extranuclear (Tsujikawa et al, 1991). Modulation of animal thionein biosynthesis, or intracellular distribution (nuclear or extranuclear), could affect DNA binding by Zn2+-requiring transcription factors and thereby regulate the activity of a large subset of genes (Zeng et al, 1991a,b).…”

Section: Metallothioneins In Other Kingdomsmentioning

confidence: 99%

Plant metallothioneins

Robinson

Tommey

Kuske

et al. 1993

Biochemical Journal

388

257

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Section: Metallothioneins In Other Kingdomsmentioning

confidence: 99%

Plant metallothioneins

Robinson

Tommey

Kuske

et al. 1993

Biochemical Journal

388

257

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“…For example, it was demonstrated that MT is localized mainly in the nucleus during development (23,24). It can be argued that, because MT is localized mainly in the nucleus during development, its limited availability to the degradation machinery (cytosol and/or lysosomes) might be a factor that can regulate its accumulation in the cell during development.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

In Vitro and In Vivo Studies on the Degradation of Metallothionein

Klaassen¹,

Choudhuri²,

McKim³

et al. 1994

Environmental Health Perspectives

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Degradation of metallothionein (MT) from rat liver was examined. Degradation of apo-MT by liver homogenate was greater than that by cytosol. At pH 5.5, degradation by homogenate was more than that at pH 7.2. These findings suggest that proteases that function at acidic pH are probably involved in MT degradation. Because lysosomes are the principal subcellular organelles that contain acid proteases (cathepsins), we compared the degradation of apo-MT by lysosomes and cytsosol. Apo-MT was degraded about 400 times faster by lysosomal fraction than by cytosolic fraction. To determine the relative importance of different cathepsins, we used different inhibitors. Leupeptin, which inhibits cathepsins B and L, inhibited the degradation of apo-MT by 80%, implying that cathepsins B and/or L might be very important in the intracellular turnover of MT. Cathepsin D appeared to be the least significant, because apo-MT degradation was reduced by about 20% by inhibiting cathepsin D. When we extended this study with purified cathepsins, we obtained the same answer, i.e., the ability of different cathepsins to degrade apo-MT was in the following order: cathepsin B >> cathepsin C > cathepsin D. While apo-MT was susceptible to degradation, ZnMT and CdMT were highly resistant to degradation. Coincubation of ZnMT or CdMT with either lysosomal extract or purified cathepsins did not result in any appreciable degradation even after 16 hr. However, longer incubations did result in some degradation, especially by purified cathepsin B. Interestingly, CdMT degraded little faster than ZnMT by both lysosomal extract as well as purified cathepsin B. These data suggest that metals protect MT from rapid proteolysis. By metal-titration study, we found that at least 5 moles of Zn equivalent/mole of MT dramatically reduced the degradation, by both lysosomal fraction and purified cathepsin B. This indicates that metal release might be a prerequisite for the initiation of degradation. Release of metals is possible in the lysosomes because the intralysosomal pH is close to 5.0. Therefore, we determined the displacement of metals (Zn) as a function of pH. We found that at a pH of 4.5, nearly 70% Zn was removed, and at pH 4.0 nearly all Zn was displaced from MT. We propose, therefore, that lysosomes are probably important in the in vivo degradation of MT, and that metal release is a prerequisite for degradation. With the release of metals in the acidic pH of lysosomes, MT becomes more susceptible to degradation, which is probably accomplished by the cathepsins, in particular cathepsin B and/or L. The in vivo study, however, suggests that there are other factors, too, in addition to metal composition and pH, that may have profound effect on determining the half-lives of various forms of MT, at various stages of development. -Environ Health Perspect 102(Suppl 3): 141-146 (1994).

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“…and in mechanisms controlling growth, differentiation and proliferation of cells, explicating their nuclear vs. cytoplasmic localization (Dziegiel, 2004). MTs are not only cytoplasmic protein, but also accumulate in lysosomes, yet could be transported to the nucleus and to the intermembrane space of mitochondria (Tsujikawa et al, 1991;Ye et al, 2001). Notably, they are also not merely intracellular, and could be exported from cells and absorbed by other cells via a receptor-mediated mechanism, in which the protein remains in an endocytotic compartment and the metal could be transported to the cytosol (Moltedo et al, 2000;Wolff et al, 2006;Hao et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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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Localization of metallothionein in nuclei of growing primary cultured adult rat hepatocytes

Cited by 116 publications

References 10 publications

Plant metallothioneins

Plant metallothioneins

In Vitro and In Vivo Studies on the Degradation of Metallothionein

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

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