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Proliferative and apoptotic activities of homocysteine: new mechanisms of action in vascular smooth muscle cells
Author(s) -
Rezk Bashir M,
Reed Ryan E,
Guidry Jesse J,
Lucchesi Pamela A
Publication year - 2008
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.22.1_supplement.747.10
Subject(s) - apoptosis , homocysteine , hyperhomocysteinemia , vascular smooth muscle , cofilin , microbiology and biotechnology , chemistry , biology , medicine , cancer research , endocrinology , cell , biochemistry , actin cytoskeleton , cytoskeleton , smooth muscle
Hyperhomocysteinemia is a risk factor for atherosclerosis. This study investigated molecular mechanisms by which homocysteine alters rat aortic vascular smooth muscle cell (VSMC) function. Low‐passage VSMC were treated for 24 hr with a pathophysiological level of homocysteine (150 μM). Paradoxically, homocysteine increased both VSMC proliferation and apoptosis. Proteomic analysis indicated that homocysteine induced a marked increased in cofilin and galectin‐1. Interestingly, homocysteine‐induced VSMC motility was associated with high expression of cofilin. On the other hand, immunocytochemistry results showed that the expression of galectin‐1 is co‐localized to apoptotic cells. The link between galectin‐1 and apoptosis was related to high expression of the proapoptotic Bax‐1. Conversely, the apoptotic effect of homocysteine involved activation of caspase‐3 and PARP cleavage. These results demonstrate for the first time that the proliferative and migratory responses to homocysteine were associated with high expression of cofilin, whereas the apoptotic pathway was associated with high levels of galectin‐1 and increased Bax‐1 expression, caspase‐3 activation and PARP cleavage to its active form. This novel finding may form a basis for new therapeutic strategies for treatment of atherosclerosis. Supported by HL056046 and P20RR18766 (PAL).