Abstract
Metallothioneins (MTs) are ubiquitous low molecular weight proteins characterized by their abundant content of cysteines. Two MT isoforms, MT-I and MT-II, are expressed coordinately in all mammalian tissues. In the CNS, MT-I and MT-II are conspicuously absent from neuronal populations, yet abundant in fibrous and protoplasmic astrocytes. A newly identified brain- specific MT gene, MT-III, is predominantly expressed in zinc-containing neurons of the hippocampus and absent from glial elements. MTs have been implicated as regulator molecules in gene expression, homeostatic control of cellular metabolism of metals, and cellular adaptation to stress. MTs store and release essential metals, such as zinc and copper, maintaining the low intracellular concentration of free essential metals. Thus, MTs fulfill a regulatory rapacity and influence transcription, replication, protein synthesis, metabolism, as well as other zinc-dependent biological processes. Because MT-III is particularly abundant in zinc-containing neurons of the hippocampus, it is likely to play an important role in neuromodulation by zinc-containing neurons and to act as a sink for free zinc. It may also play an etiologic role in various pathophysiological conditions associated with increased extracellular zinc. Studies demonstrating that MT-III prevents neuronal sprouting in vitro, appears to be down-regulated in Alzheimer's disease, and that MT-III 'knockout' mice appear highly sensitive to cannot- induced seizures have focused growing attention on the etiologic rule of MT- III in neurodegeneration.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1129-1136 |
| Number of pages | 8 |
| Journal | FASEB Journal |
| Volume | 10 |
| Issue number | 10 |
| State | Published - 1996 |
| Externally published | Yes |
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Keywords
- glutathione
- induction
- nitric oxide
- zinc
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Cell Biology
Cite this
The functional significance of brain metallothioneins. / Aschner, Michael.
In: FASEB Journal, Vol. 10, No. 10, 1996, p. 1129-1136.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The functional significance of brain metallothioneins
AU - Aschner, Michael
PY - 1996
Y1 - 1996
N2 - Metallothioneins (MTs) are ubiquitous low molecular weight proteins characterized by their abundant content of cysteines. Two MT isoforms, MT-I and MT-II, are expressed coordinately in all mammalian tissues. In the CNS, MT-I and MT-II are conspicuously absent from neuronal populations, yet abundant in fibrous and protoplasmic astrocytes. A newly identified brain- specific MT gene, MT-III, is predominantly expressed in zinc-containing neurons of the hippocampus and absent from glial elements. MTs have been implicated as regulator molecules in gene expression, homeostatic control of cellular metabolism of metals, and cellular adaptation to stress. MTs store and release essential metals, such as zinc and copper, maintaining the low intracellular concentration of free essential metals. Thus, MTs fulfill a regulatory rapacity and influence transcription, replication, protein synthesis, metabolism, as well as other zinc-dependent biological processes. Because MT-III is particularly abundant in zinc-containing neurons of the hippocampus, it is likely to play an important role in neuromodulation by zinc-containing neurons and to act as a sink for free zinc. It may also play an etiologic role in various pathophysiological conditions associated with increased extracellular zinc. Studies demonstrating that MT-III prevents neuronal sprouting in vitro, appears to be down-regulated in Alzheimer's disease, and that MT-III 'knockout' mice appear highly sensitive to cannot- induced seizures have focused growing attention on the etiologic rule of MT- III in neurodegeneration.
AB - Metallothioneins (MTs) are ubiquitous low molecular weight proteins characterized by their abundant content of cysteines. Two MT isoforms, MT-I and MT-II, are expressed coordinately in all mammalian tissues. In the CNS, MT-I and MT-II are conspicuously absent from neuronal populations, yet abundant in fibrous and protoplasmic astrocytes. A newly identified brain- specific MT gene, MT-III, is predominantly expressed in zinc-containing neurons of the hippocampus and absent from glial elements. MTs have been implicated as regulator molecules in gene expression, homeostatic control of cellular metabolism of metals, and cellular adaptation to stress. MTs store and release essential metals, such as zinc and copper, maintaining the low intracellular concentration of free essential metals. Thus, MTs fulfill a regulatory rapacity and influence transcription, replication, protein synthesis, metabolism, as well as other zinc-dependent biological processes. Because MT-III is particularly abundant in zinc-containing neurons of the hippocampus, it is likely to play an important role in neuromodulation by zinc-containing neurons and to act as a sink for free zinc. It may also play an etiologic role in various pathophysiological conditions associated with increased extracellular zinc. Studies demonstrating that MT-III prevents neuronal sprouting in vitro, appears to be down-regulated in Alzheimer's disease, and that MT-III 'knockout' mice appear highly sensitive to cannot- induced seizures have focused growing attention on the etiologic rule of MT- III in neurodegeneration.
KW - glutathione
KW - induction
KW - nitric oxide
KW - zinc
UR - http://www.scopus.com/inward/record.url?scp=0029845691&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029845691&partnerID=8YFLogxK
M3 - Article
C2 - 8751715
AN - SCOPUS:0029845691
VL - 10
SP - 1129
EP - 1136
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 10
ER -