Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis.

Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Research Abstract Details 

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Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Abstract Text:

OBJECTIVE: L-homocysteine and/or L-homocystine interact in vivo with albumin and other extracellular proteins by forming mixed-disulfide conjugates. Because of its extremely rich cysteine content, we hypothesized that metallothionein, a ubiquitous intracellular zinc-chaperone and superoxide anion radical scavenger, reacts with L-homocysteine and that homocysteinylated-metallothionein suffers loss of function. METHODS AND RESULTS: 35S-homocysteinylated-metallothionein was resolved in lysates of cultured human aortic endothelial cells in the absence and presence of reduced glutathione by SDS-PAGE and identified by Western blotting and phosphorimaging. Using zinc-Sepharose chromatography, L-homocysteine was shown to impair the zinc-binding capacity of metallothionein even in the presence of reduced glutathione. L-Homocysteine induced a dose-dependent increase in intracellular free zinc in zinquin-loaded human aortic endothelial cells within 30 minutes, followed by the appearance of early growth response protein-1 within 60 minutes. In addition, intracellular reactive oxygen species dramatically increased 6 hours after L-homocysteine treatment. In vitro studies demonstrated that L-homocysteine is a potent inhibitor of the superoxide anion radical scavenging ability of metallothionein. CONCLUSIONS: These studies provide the first evidence that L-homocysteine targets intracellular metallothionein by forming a mixed-disulfide conjugate and that loss of function occurs after homocysteinylation. The data support a novel mechanism for disruption of zinc and redox homeostasis.

Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Publishing Authors By Initials

For similar inorganic chemicals: elements: metals, heavy: zinc research abstracts see: inorganic chemicals: elements: metals, heavy: zinc research

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Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Arteriosclerosis, thrombosis, and vascular biology

VOLUME: 27

Page Numbers: 49-54

Journal Abbreviation: Arterioscler. Thromb. Vasc. Bi

ISSN: 1524-4636

DAY: 2

MONTH: 11

YEAR: 2006

Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9505803

Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Keywords Mesh Terms:

KEYWORDS: Zinc

MESH TERMS: metabolism

Chemical & Substance for Abstract: Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Information

Substance Name: Metallothionein

Registry Number: 9038-94-2

Grant and Affiliation Information for Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis.

AFFILIATION: Department Cell Biology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL52234

ACRONYM: HL

MEDLINETA: Arterioscler Thromb Vasc Biol

REFSOURCE: Arterioscler Thromb Vasc Biol. 2007 Jan;

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