Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats.

Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Research Abstract Details 

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Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Abstract Text:

Muyao Li,Jen-Fu Chiu,Brooke T Mossman,Naomi K Fukagawa,

Manganese-superoxide dismutase (MnSOD) is one of the major cellular antioxidant defense systems. To study the effect of age on the regulation of MnSOD in the vasculature, we compared MnSOD expression and its transcriptional regulation in explanted vascular smooth muscle cells (VSMC) isolated from old (24 months old) versus young (6 months old) rats and grown in a normal (5 mM) or high (12.5 and 25 mM) glucose or tumor necrosis factor alpha (5 ng/ml) environment to induce oxidative stress. Both MnSOD protein and activity were reduced in VSMC from old compared with young animals. FOXO3a, a member of the family of Forkhead transcription factors, interacted with the promoter of the rat MnSOD gene at a specific binding site. Inhibition of FOXO3a transcription with small interfering RNA led to a reduction in MnSOD gene expression. VSMC from old rats had increased phosphorylated FOXO3a at Ser(253), which paralleled the reduction of MnSOD protein. Treatment of VSMC with 5 nm insulin-like growth factor-1 induced phosphorylation of Akt and FOXO3a over time, repressing FOXO3a DNA binding and consequently MnSOD gene expression. Furthermore, Akt activity was selectively increased in VSMC from the old, supporting the hypothesis that increased age-related Akt activity might be responsible for the phosphorylation and inactivation of FOXO3a, which in turn down-regulates MnSOD transcription.

Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Publishing Authors By Initials

M Li,JF Chiu,BT Mossman,NK Fukagawa,

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Journal Published:

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

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 40429-39

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 1

MONTH: 11

YEAR: 2006

Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats.

AFFILIATION: Departments of Medicine, Pathology, and Biochemistry, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL067004

ACRONYM: HL

MEDLINETA: J Biol Chem

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