Bacterial endotoxin-induced expression of metallothionein genes in rat brain, as revealed by in situ hybridization

The metal-binding protein, metallothionein (MT) has been found to be primarily produced by astrocytes in the rat and human brain. This review discusses the relationship of glial MT to the distribution of metals in the brain, possible roles of MT in the regulation of glial enzymes and other glial proteins, and the possible role of a subset of MT-immunoreactive glia, the Gomori-positive astrocytes, in defending against toxic metals that enter the brain via circumventricular organs. The possible involvement of MT-containing astrocytes in degenerative brain disorders in also briefly discussed.

mentioning

confidence: 99%

Glial Metallothionein

Young¹

1994

“…ependymal cells, pia mater, arachnoid, and some glial cells, though the MT induction was not sufficient to signficantly affect the overall MT level of the brain. Intracerebroventricular administration of Zn has also been reported to significantly increase brain MT protein lev els [4,22], By contrast, in several studies using intraperitoneal injection, peripheral administra tion of Zn or Cd (300 pmol Zn/kg, rat [9]; 4.5 pmol Cd/kg, mouse [11]; 75 pmol Zn/kg, rat [12], and 115 pmol Zn/kg, rat [22]) elicited no significant increase in brain MT protein levels. Moreover, rat brain levels of MT mRNAs did not respond appreciably to changes in dietary levels of Cu and Zn [23].…”

Section: Induction By Heavy Metalsmentioning

confidence: 89%

“…Although the basal expression of MT mRNAs in the brain is detectable using Northern blot analysis [6] and solution hy bridization [ 11 ], no significant signal has been detected by in situ hybridization [12]. How ever, constitutive transcription and transla tion of MT has been demonstrated, since MT proteins have been isolated from the un treated brain [4,8], Regarding the regional distribution of MT proteins, MT content has been reported as being highest in the hippo campus and midbrain, and lowest in the fron tal cortex and pons plus medulla oblongata [13].…”

Section: Regional and Cellular Expressionmentioning

confidence: 99%

“…Other Inducers Inducibility by glucocorticoids [2,3,11], bacterial endotoxins or LPS [6,12,28], Xirradiation [29] and immobilization stress [7,13] has been recognized in the brain. Since the relevant kinetic analyses have not always been established, their effectiveness in the brain as compared with the peripheral tissues has usually not been clarified.…”

Section: Induction By Heavy Metalsmentioning

confidence: 99%

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Brain Metallothionein Gene Expression and Regulation

Saijoh¹,

Katsuyama²,

Sumino³

1994

Metallothionein (MT) gene expression in the brain has been most thoroughly studied using rodents. Although MT is considered to be a ''housekeeping'' protein even in the brain, the basal MT mRNA expression level is not always high. Differences in the responses of rats and mice have made it difficult to interpret the data. Moreover, the response to inducers is not always apparent, probably because the brain is protected by the blood-brain barrier and initial responses to inducers in peripheral tissues modulate their accumulation in the brain. A relatively high content of MT protein in the brain might be sufficient to elicit minute alterations in the level of inducers. Nonetheless, regulation of MT gene expression in the brain seems to be important in e.g. maintaining the levels of trace elements and controlling redox potentials. The localization and utilization of trans elements such as MTF-I and MEP-I in the brain will provide new aspects for study. The high homology among MT isoforms with respect to nucleotide as well as amino acid sequences has made it difficult to obtain cDNA probes or antibodies capable of distinguishing MT isoforms. Thus, their cross-reactivity might make changes in MT mRNAs appear minimal when MT isoforms are differently regulated. The rapid developments in methodology permitting sensitive, rapid, high-resolution analysis could clarify the background of tissue- and cell-specific gene regulation as well as differential induction.

“…Astroglial cells have been shown to contain MT by immunohistochemi cal staining [18,[20][21][22][23][24] or in situ hybridiza tion [19]. Intraperitoneal or intragastric ad ministration of zinc or cadmium does not increase the brain MT level [11,13,15,19] as markedly as the liver MT level. In the case of cadmium ions, this may in part be attribut able to the blood-brain barrier [27], Brain MT induction is prominent, however, when zinc is administered intracerebrally [13] or when animals are exposed to mercury vapor [25].…”

Section: Introductionmentioning

confidence: 99%

Induction of Metallothionein in Astrocytes by Cytokines and Heavy Metals

Sawada

Kikuchi

Shibutani³

et al. 1994

Immunohistochemical staining of human and rat brains for metallothionein (MT) using a monoclonal anti-MT antibody (MT45) revealed that protoplasmic astrocytes, which are densely localized in the gray matter, contain high levels of MT. Human U373MG astrocytoma cells were stimulated with interleukin (IL)-1 or heavy metals to produce MT. When expression of MT in U373MG cells was analyzed by Northern blotting or indirect immunofluorescence using the MT45 antibody, it was found that IL-1 (≧ 10 U/ml), CdCl₂ (50 µM) and high concentrations of ZnCl₂ (500 µM) induced marked biosynthesis of MT. IL-6 (up to 3,000 U/ml) and lower concentrations of ZnCl₂ (10–50 µM), however, showed little inducing activity. Hippocampal astrocytes in primary culture produced a relatively high basal level of MT. The MT level increased in response to addition of IL-1 (≧ 10 U/ml), ZnCl₂ (50 µM) and CdCl₂ (5 µM). However, the increase induced by IL-6 (1,000 U/ml) was not very marked. The in vivo induction of MT in the brain by cytokines is not fully understood. However, our data and other indirect evidence suggest that IL-1 may be a potent stimulator of MT induction in astrocytes. Furthermore, the astrocytoma cell line, U373MG, is a suitable in vitro system to analyze the expression of MT in astrocytes.