Skip Navigation

Cardiovascular Research 2001 52(2):328-336; doi:10.1016/S0008-6363(01)00376-5
© 2001 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Zhang, Q.
Right arrow Articles by Wang, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, Q.
Right arrow Articles by Wang, X.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2001, European Society of Cardiology

Effects of homocysteine on murine splenic B lymphocyte proliferation and its signal transduction mechanism

Qin Zhanga, Xiaokun Zenga, Jingxuan Guoa and Xian Wanga,b,*

aInstitute of Vascular Medicine, Third Hospital, Beijing 100083, People's Republic of China
bDepartment of Physiology, Health Science Center, Peking University, No. 38, Xue Yuan Road, Beijing 100083, People's Republic of China

* Corresponding author. Tel.: +86-10-6209-1443; fax: +86-10-6201-7700 xwang{at}mail.bjmu.edu.cn

Objective: Elevated plasma homocysteine (Hcy) levels have been defined as an increased risk of atherosclerosis. However, the mechanisms that Hcy induces the development of atherosclerosis are not fully understood. Therefore, effect of Hcy on B lymphocyte proliferation and its cellular mechanism were examined in normal and hyperhomocysteinemia ApoE-knockout mice. Methods: Mouse B lymphocytes were incubated with Hcy, related compounds and/or antioxidants and/or inhibitors of PKC, p38 MAPK, NF-{kappa}B in the presence or absence of lipopolysaccharide. DNA synthesis, production of reactive oxygen species was measured. Results: Hcy (0.1–3.0 mM) and other compounds with thiol (–SH), such as cysteine and glutathione significantly increased resting and lipopolysaccharide-induced B lymphocyte proliferation. ApoE-knockout mice with hypercysteinemia (plasma Hcy levels were 20.3±2.9 vs. 2.6±0.6 µM in control, P<0.05) had a significant promotion of B cell proliferation in response to lipopolysaccharide. Hcy also increased intracellular reactive oxygen species production. Radical scavengers reduced Hcy-induced B lymphocyte proliferation. The promotion of Hcy was significantly inhibited by inhibitors of PKC (calphostin C and RO-31-8220), p38 MAPK (SB 202190 and PD 169316) and NF-{kappa}B (pyrrolidine dithiocarbamate). Conclusions: The reactive oxygen species generated by thiol (–SH) auto-oxidation of Hcy are essential, and PKC, p38 MAPK and NF-{kappa}B are involved in the Hcy-induced B lymphocyte proliferation. Hyperhomocysteinemia may increase B lymphocyte susceptibility to inflammatory progression of atherosclerotic lesions.

KEYWORDS Atherosclerosis; Free radicals; Immunology; Infection/inflammation; Signal transduction


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.