Oxygen free radicals and metallothionein

Sato, Masao; Bremner, I.

doi:10.1016/0891-5849(93)90029-t

Cited by 809 publications

(417 citation statements)

References 105 publications

Supporting

Mentioning

396

Contrasting

Unclassified

Order By: Relevance

“…MTs bind zinc and copper and presumably function in metal ion regulation and detoxification in peripheral tissues as well as in the CNS (4,33). Early studies suggested that MT-I ϩ II could have significant antioxidant capacity and functions (32,55,63), and recent reports with transgenic mice overexpressing these MT isoforms and with MT-I ϩ II KO mice fully support such roles (22,28,37,39,40,42,43). 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.…”

Section: Introductionmentioning

confidence: 74%

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

Carrasco

Giralt

Penkowa

et al. 2000

Experimental Neurology

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 74%

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

Carrasco

Giralt

Penkowa

et al. 2000

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…10,60,61 MTs serve multiple other roles, including both heavy metal detoxification, Zn 2+ ion homeostasis, and possibly oxidative stress control. 62 Given the importance of MTs, structure-function correlations of the involved metal-binding clusters is a natural step forward.…”

Section: Biological Implicationsmentioning

confidence: 99%

The building blocks of metallothioneins: heterometallic Zn2+ and Cd2+ clusters from first-principles calculations

Jensen

Rykær

2010

Dalton Trans.

View full text Add to dashboard Cite

Electronic structures of Zn 2+ and Cd 2+ thiolate clusters found in metallothioneins (MT) have been obtained using density functional theory. We have found that the inherent asymmetry of cluster architectures gives rise to seven distinct metal sites. Whereas the non-strained bond lengths of such tetrathiolate complexes are found to be 2.60Å and 2.39Å for Cd-S and Zn-S, in the MT clusters four characteristic terminal and bridging bonds are observed with average lengths 2.55Å (Cd-S t ); 2.35Å (Zn-S t ); 2.62Å (Cd-S b ); and 2.42Å (Zn-S b ). For each stoichiometry of Zn 2+ and Cd 2+ , all possible isomers have been characterized and ranked according to relative free energy and metal ion selectivity. The most stable distribution at low Cd 2+ concentration is computed to be Zn 4 + CdZn 2 , whereas at 2 : 1 Cd 2+ : Zn 2+ concentration, only heteroclusters are thermodynamically stable, explaining experimental data. The presence of two different clusters in MTs must and can be rationalized already in their intrinsic differences. The results indicate that the asymmetry allows for Zn 2+ transfer to various molecular targets having different thresholds for Zn 2+ binding, while maintaining detoxification sites.

show abstract

“…As expected from the above studies, a dramatic upregulation of MT-1&2 was observed in clinically symptomatic GFAP-IL6 (27,114), GFAP-TNF (36), GFAP-IL3 and GFAP-IFNα (115) mice. In some of these mice it has clearly been demonstrated that oxidative stress is increased, and since MT-1&2 are potent antioxidant proteins and are induced by oxidative stress (7,116,117), it is likely that this cytokine-driven MT-1&2 expression is at least in part related to tissue injury rather than to a specific gene regulation. Nevertheless, data obtained in IL-6-null mice have supported a specific role of IL-6 in MT-1&2 gene regulation (62,66,118).…”

Section: Transgenic Mice Show That Metallothionein-1and2 Are Essential mentioning

confidence: 99%

Metallothioneins and brain injury: What transgenic mice tell us

Hidalgo

2004

Environ Health Prev Med

View full text Add to dashboard Cite

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.

show abstract

Oxygen free radicals and metallothionein

Cited by 809 publications

References 105 publications

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

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

The building blocks of metallothioneins: heterometallic Zn2+ and Cd2+ clusters from first-principles calculations

Metallothioneins and brain injury: What transgenic mice tell us

Contact Info

Product

Resources

About