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β‐lactoglobulin plays a provocative role in lymphocyte proliferation
Author(s) -
Chen Wen Liang,
Liu Wei Ting,
Ko Li Pin,
Mao Simon J.T.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a961
Subject(s) - chemistry , cell growth , flow cytometry , receptor , dimer , cell , cell cycle , denaturation (fissile materials) , biochemistry , biophysics , microbiology and biotechnology , biology , organic chemistry , nuclear chemistry
β‐lactoglobulin (β‐LG) is one of the major proteins moieties of bovine whey proteins, in which β‐LG consist of about 50 % of the whey or about 10~15 % of total milk proteins. β‐LG is sensitive to thermal denaturation, forming dimer and polymers upon the heating greater then 80 □ over time. Previous, we have extensively studied some major physical and biochemical properties of heated β‐LG, but its physiologic effect has not been elucidated. In the present study, we show that β‐LG possesses a potent cell proliferation activity for hybridoma lymphocytes. Thermally denatured β‐LG, however, did not show this effect. Using antibody‐affinity column to remove β‐LG from milk proteins, the proliferation activity of β‐LG‐deficient milk was substantially reduced as compared to the whole milk. To further study the influence of β‐LG conformation on cell proliferation, we chemically modified (carboxymethylation and acetylation) the β‐LG to disrupt the disulfide linkages, the proliferation activity was not observed. Therefore, we suppose that conformation of β‐LG plays a key role to induce cell proliferation. To demonstrate β‐LG may stimulate the cell proliferation via receptor‐mediated process; we show the binding of β‐LG to cell surface using flow cytometry and confocal microscopy. In addition, we have successfully isolated and identified the β‐LG receptor using both HPLC and β‐LG affinity column. β‐LG was able to increase of the cyclin A, which participates in G2 phase of cell cycle. Taken together, β‐LG acts as “growth factor” in the lymphocytes via a receptor‐mediated mechanism.