Metallothionein in Developing Human Brain

Suzuki, Keiji; Nakajima, Katsuyuki; Otaki, Noriko; Kimura, Masami

doi:10.1159/000109544

Cited by 35 publications

(21 citation statements)

References 7 publications

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“…This is in agreement with previous observations reporting that MT is expressed only in minute amounts in the embryonic and neonatal rodent brain and that its expression progressively increases during the first weeks w x of the postnatal development 43,59 . In addition to age-related differences, MT is not uniformly distributed through the normal CNS and regional differences in the MT prow x tein and MT mRNA content 14,20,21,25,28 , as well as in w x the distribution of MT-positive cells 8,28 , have been described.…”

Section: Distribution Of Mt In Normal Animalssupporting

confidence: 93%

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

et al. 1997

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Jimpy is a shortened life-span murine mutant whose genetic disorder results in severe pathological alterations in the CNS, including Ž . hypomyelination, oligodendrocyte death and strong astroglial and microglial reaction. The knowledge of metallothionein MT regulation in the CNS and especially of MT presence in specific glial cell types under pathological conditions is scarce. In the present study, immunocytochemical detection of MT-I q II has been performed in spinal cord sections from 10-12-and 20-22-day-old jimpy and normal animals. The identification of MT-positive glial cells was achieved through double labeling combining MT immunocytochemistry and selective markers for oligodendrocytes, astrocytes and microglia. MT was found in glial cells and was present in the spinal cord of jimpy and normal mice at both ages, but there were remarkable differences in MT expression and in the nature of MT-positive glial cells depending on the type of mouse. The number of MT-positive cells was higher in jimpy than in normal spinal cords. This was apparent in all spinal cord areas, although it was more pronounced in white than in the gray matter and at 20-22 days than at 10-12 days. The mean Ž . Ž . number of MT-positive glia in the jimpy white matter was 1.9-fold 10-12 days and 2.4-fold 20-22 days higher than in the normal one. Astrocytes were the only parenchymal glial cells that were positively identified as MT-producing cells in normal animals. Interestingly, MT in the jimpy spinal cord was localized not only in astrocytes but also in microglial cells. The occurrence of MT induction in relation to reactive astrocytes and microglia, and its role in neuropathological conditions is discussed. q 1997 Elsevier Science B.V.

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Section: Distribution Of Mt In Normal Animalssupporting

confidence: 93%

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

et al. 1997

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“…In mice, MT-IV is not detected prior to day 7 postpartum (17). Furthermore, MT is not detected in human fetal brain in less than the 35-week-old fetus (89). The mechanisms responsible for developmental regulation of MT transcription have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Metallothionein Gene Transcription

Moilanen¹,

Fukushige²,

Freedman³

1999

Journal of Biological Chemistry

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Metallothioneins are small, cysteine-rich proteins that function in metal detoxification and homeostasis. Metallothionein transcription is controlled by cell-specific factors, as well as developmentally modulated and metal-responsive pathways. By using the nematode Caenorhabditis elegans as a model system, the mechanism that controls cell-specific metallothionein transcription in vivo was investigated. The inducible expression of the C. elegans metallothionein genes, mtl-1 and mtl-2, occurs exclusively in intestinal cells. Sequence comparisons of these genes with other C. elegans intestinal cell-specific genes identified multiple repeats of GATA transcription factor-binding sites (i.e. GATA elements). In vivo deletion and site-directed mutation analyses confirm that one GATA element in mtl-1 and two in mtl-2 are required for transcription. Electrophoretic mobility shift assays show that the C. elegans GATA transcription factor ELT-2 specifically binds to these elements. Ectopic expression of ELT-2 in non-intestinal cells of C. elegans activates mtl-2 transcription in these cells. Likewise, mtl-2 is not expressed in nematodes in which elt-2 has been disrupted. These results indicate that cell-specific transcription of the C. elegans metallothionein genes is regulated by the binding of ELT-2 to GATA elements in these promoters. Furthermore, a model is proposed where ELT-2 constitutively activates metallothionein expression; however, a second metal-responsive factor prevents transcription in the absence of metals. Metallothioneins (MT)1 are a family of structurally related, low molecular weight, cysteine-rich proteins (1). The precise physiological role of MT has not been elucidated. However, evolutionary conservation across many phyla suggests that it serves important roles in cell function. Proposed roles include the following: (a) participation in maintaining the homeostasis of essential trace metals; (b) sequestration of toxic metals, such as cadmium and mercury; (c) acting as a reservoir of essential metals that can be donated to other metalloproteins; and (d) protection against intracellular oxidative damage (2).Exposure of cultured cells or whole organisms to transition metals, ionizing radiation, heat-shock, or oxidative stress induces MT transcription (1, 3-5). Metallothioneins typically occur in multigene families. The mammalian MT family consists of four members designated MT-I to MT-IV (6). It has been commented that all organisms express MT or MT-like proteins. However, not all tissues within an organism will express all MT isoforms. Numerous studies indicate that individual MT family members display specific cellular patterns of expression. Typically, MT-I and MT-II genes are coordinately expressed. It has been shown, however, that MT-2A mRNA levels do not increase in response to cadmium exposure in human proximal tubule cells (7). Expression of the human MT-I B , MT-I E , MT-I F , and MT-I G genes varies in a cell line-specific manner in response to transition metals (8 -12). Mouse MT-I is weakly exp...

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“…Studies of in situ hybridization (21, 24-28) and immunohistochemistry (19,21,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), have demonstrated that MT-1&2 expression occurs throughout the brain and spinal cord, and that the principal cellular source is the astrocyte, particularly following injury. Significant MT-1&2 expression is also found in ependymal cells, epithelial cells of the choroid plexus, meningeal cells of the pia mater and endothelial cells of blood vessels, while neurons appear to express very low levels.…”

Section: Metallothionein-1and2 Are Preferentially Expressed In Reactivementioning

confidence: 99%

Metallothioneins and brain injury: What transgenic mice tell us

Hidalgo

2004

Environ Health Prev Med

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In rodents, the metallothionein (MT) family is composed of four members, MT-1 to MT-4. MT-1&2 are expressed in virtually all tissues including those of the Central Nervous System (CNS), while MT-3 (also called Growth Inhibitory Factor) and MT-4 are expressed prominently in the brain and in keratinizing epithelia, respectively. For the understanding of the physiological functions of these proteins in the brain, the use of transgenic mice has provided essential information. Results obtained in MT-1&2-null mice and in MT-1-overexpressing mice strongly suggest that these MT isoforms are important antioxidant, anti-inflammatory and antiapoptotic proteins in the brain. Results in MT-3-null mice show a very different pattern, with no support for MT-1&2-like functions. Rather, MT-3 could be involved in neuronal sprouting and survival. Results obtained in a model of peripheral nervous system injury also suggest that MT-3 could be involved in the control of nerve growth.

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Metallothionein in Developing Human Brain

Cited by 35 publications

References 7 publications

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

Regulation of Metallothionein Gene Transcription

Metallothioneins and brain injury: What transgenic mice tell us

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