Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells.

Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Research Abstract Details 

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Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Abstract Text:

Xiaohua Jiang,Fan Yang,Eugen Brailoiu,Hieronim Jakubowski,Nae J Dun,Andrew I Schafer,Xiaofeng Yang,William Durante,Hong Wang,

OBJECTIVE: We previously reported that homocysteine (Hcy) inhibits endothelial cell (EC) growth and promotes vascular smooth muscle cell (VSMC) proliferation. This study characterized and directly compared Hcy transport in cultured human aortic ECs (HAECs) and smooth muscle cells (HASMCs). METHODS AND RESULTS: Hcy (10 micromol/L) was transported into both cell types in a time-dependent fashion but was approximately 4-fold greater in HASMCs, and is nonstereoenantiomer specific. Hcy transport in HAECs had a Michaelis-Menten constant (Km) of 39 micromol/L and a maximal transport velocity (Vmax) of 873 pmol/mg protein/min. In contrast, Hcy transport in HASMCs had a lower affinity (Km = 106 micromol/L) but a higher transport capacity (Vmax = 4192 pmol/mg protein/min). Competition studies revealed that the small neutral amino acids tyrosine, cysteine, glycine, serine, alanine, methionine, and leucine inhibited Hcy uptake in both cell types, but the inhibition was greater for tyrosine, serine, glycine, and alanine in HAECs. Sodium-depletion reduced Hcy transport to 16% in HAECs and 56% in HASMCs. Increases in pH from 6.5 to 8.2 or lysosomal inhibitors blocked Hcy uptake only in HAECs. In addition, Hcy shares carrier systems with cysteine, in a preferable order of alanine-serine-cysteine (ASC) > aspartate and glutamate (X(AG)) = large branched-chain neutral amino acids (L) transporter systems in HAECs and ASC > L > X(AG) in HASMCs. The sodium-dependent system ASC plays a predominant role for Hcy transport in vascular cells. CONCLUSIONS: Transport system ASC predominantly mediates Hcy transport in EC and is lysosomal dependent.

Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Publishing Authors By Initials

X Jiang,F Yang,E Brailoiu,H Jakubowski,NJ Dun,AI Schafer,X Yang,W Durante,H Wang,

For similar cells: muscle cells: myocytes, smooth muscle research abstracts see: cells: muscle cells: myocytes, smooth muscle research

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MEDLINE DATE:

Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Journal Published:

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

Journal: Arteriosclerosis, thrombosis, and vascular biology

VOLUME: 27

Page Numbers: 1976-83

Journal Abbreviation: Arterioscler. Thromb. Vasc. Bi

ISSN: 1524-4636

DAY: 3

MONTH: Sep

YEAR: 2007

Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9505803

Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Keywords Mesh Terms:

KEYWORDS: Myocytes, Smooth Muscle

MESH TERMS: physiology

Chemical & Substance for Abstract: Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells. Information

Substance Name: Homocysteine

Registry Number: 454-28-4

Grant and Affiliation Information for Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cells.

AFFILIATION: Temple University School of Medicine, Department of Pharmacology, 3420 North Broad Street, Philadelphia, PA 19140, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL82774

ACRONYM: HL

MEDLINETA: Arterioscler Thromb Vasc Biol

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