The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein

Uchida, Yuzo; Takio, Koji; Titani, Koiti; Ihara, Yasuo; Tomonaga, Masanori

doi:10.1016/0896-6273(91)90272-2

Cited by 687 publications

(593 citation statements)

References 62 publications

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“…Although MT-3 was initially reported to be downregulated during AD, this is unfortunately not a consistent finding (40,41,71,76,(132)(133)(134). Whether this has to do with methodological problems (as discussed above, different antibodies give different results) or different AD etiologies is currently unclear.…”

Section: Transgenic Mice Show Different Metallothionein-3 Functionsmentioning

confidence: 97%

“…Initially regarded as a CNS-specific isoform (11, [40][41][42], it is now clear that MT-3 is expressed in other tissues, in some cases in a development-dependent manner (43)(44)(45)(46)(47)(48)(49). In addition to human and mouse brain, MT-3 has been reported in other species such as horse and cow (50), rat (51), pig (52), dog (53), and sheep (54).…”

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

confidence: 99%

“…Using antibodies raised against the unique 6-amino acid insert of MT-3/GIF, in situ hybridization, or Northern blot analysis, Uchida et al (40,42,55) observed that MT-3 expression was prominent in astrocytes but not in neurons or other brain cells. However, many other reports have not supported an astrocyte-specific MT-3 expression.…”

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

confidence: 99%

“…Although in most cases no thorough cell identification has been established by robust methods such as double labeling or use of the MT-3 KO mice as controls, in the normal brain it appears that the MT-3 mRNA signal is more consistent with neuronal than with glial cells, with astrocyte MT-3 upregulation eventually occurring following injury (26,27,36,53,(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68). In contrast to the MT-3 messenger, the MT-3 protein has been shown to be present mainly in astrocytes by a number of studies (36,40,65,66,(69)(70)(71)(72)(73)(74). Other reports, however, show MT-3 protein presence basically in neurons (63,64,(75)(76)(77).…”

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

confidence: 99%

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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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Section: Transgenic Mice Show Different Metallothionein-3 Functionsmentioning

confidence: 97%

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

confidence: 99%

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

confidence: 99%

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

confidence: 99%

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Metallothioneins and brain injury: What transgenic mice tell us

Hidalgo

2004

Environ Health Prev Med

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“…We have recently shown that the inflammatory response to glial cell death and the wound healing capacity of the CNS is severely impaired in MT-I ϩ II KO mice (49,50), suggesting a major role of these MT isoforms during CNS injury. MT-III was discovered as an inhibitory neuronal growth factor (in vitro) that appeared to be decreased in Alzheimer's disease brains (64); the latter, however, has not been confirmed (2,9,21). So far, the results obtained in MT-III KO mice suggest this MT isoform would have a rather neuroprotective role in some brain areas (20).…”

Section: Introductionmentioning

confidence: 99%

Metallothioneins Are Upregulated in Symptomatic Mice with Astrocyte-Targeted Expression of Tumor Necrosis Factor-α

Carrasco

Giralt

Penkowa

et al. 2000

Experimental Neurology

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Transgenic mice expressing TNF-␣ under the regulatory control of the GFAP gene promoter (GFAP-TNF␣ mice) exhibit a unique, late-onset chronic-progressive neurological disorder with meningoencephalomyelitis, neurodegeneration, and demyelination with paralysis. Here we show that the metallothionein-I ؉ II (MT-I ؉ II) isoforms were dramatically upregulated in the brain of symptomatic but not presymptomatic GFAP-TNF␣ mice despite TNF-␣ expression being present in both cases. In situ hybridization analysis for MT-I RNA and radioimmunoassay results for MT-I ؉ II protein revealed that the induction was observed in the cerebellum but not in other brain areas. Increased MT-I RNA levels occurred in the Purkinje and granular neuronal layers of the cerebellum but also in the molecular layer. Reactive astrocytes, activated rod-like microglia, and macrophages, but not the infiltrating lymphocytes, were identified as the cellular sources of the MT-I ؉ II proteins. In situ hybridization for MT-III RNA revealed a modest increase in the white matter of the cerebellum, which was confirmed by immunocytochemistry. MT-III immunoreactivity was present in cells which were mainly round or amoeboid monocytes/macrophages. The pattern of expression of the different MT isoforms in the GFAP-TNF␣ mice differed substantially from that described previously in GFAP-IL6 mice, demonstrating unique effects associated with the expression of each cytokine. The results suggest that the MT expression in the CNS reflects the inflammatory response and associated damage rather than a direct role of the TNF-␣ in their regulation and support a major role of these proteins during CNS injury.

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Metallothionein isoform 3 expression in the human prostate and cancer-derived cell lines

Garrett¹,

Sens²,

Shukla³

et al. 1999

Prostate

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BACKGROUND Expression of metallothionein isoform 3 (MT‐3) was initially reported to be confined to neural tissues. However, it was recently demonstrated that MT‐3 is expressed in epithelial cells of the human kidney. This motivated the current examination of the expression of MT‐3 in the human prostate. METHODS Immunohistochemistry (IHC) was used to localize the expression of MT‐3, RT‐PCR to determine the expression of MT‐3 mRNA, and Western blot analysis to determine the level of MT‐3 protein. RESULTS Selected epithelial and stromal cells of the normal human prostate were shown to have low levels of MT‐3 expression. MT‐3 was increased in prostatic intraepithelial neoplasia (PIN) lesions and further increased in a highly variable fashion in prostatic adenocarcinoma. In some adenocarcinomas, MT‐3 expression exceeded that of nerve. Three cell culture models of prostate cancer were also shown to variably express MT‐3. Restriction enzyme analysis confirmed the expression of MT‐3 in the cells and tissues. CONCLUSIONS MT‐3 is expressed in the normal human prostate, and expression is enhanced and highly variable in PIN lesions and primary prostate cancer cells. The variable nature of MT‐3 expression was also noted in commonly utilized prostate cancer cell lines. Prostate 41:196–202, 1999. © 1999 Wiley‐Liss, Inc.

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The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein

Cited by 687 publications

References 62 publications

Metallothioneins and brain injury: What transgenic mice tell us

Metallothioneins and brain injury: What transgenic mice tell us

Metallothioneins Are Upregulated in Symptomatic Mice with Astrocyte-Targeted Expression of Tumor Necrosis Factor-α

Metallothionein isoform 3 expression in the human prostate and cancer-derived cell lines

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