Homocysteine andα-Lipoic Acid Regulate p44/42 MAP Kinase Phosphorylation in NIH/3T3 Cells

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Abstract
Biological thiols can regulate cell signal transduction. The effects of two biothiols, (Hcy), a risk factor for cardiovascular disease, and alpha-lipoic acid (alpha LA), a therapeutic antioxidant, on p44/42 mitogen-activated protein kinases (MAPK) phosphorylation were examined in NIH/3T3 fibroblasts. Cells grown in serum-containing media had constitutive levels of MAPK phosphorylation as determined by Western blot analysis using the phospho-specific MAPK antibody. Treatment of cells with 20 mu M Hcy for 0-60 min resulted in a transient enhancement of MAPK phosphorylation. In contrast, 20 mu M alpha LA inhibited serum-mediated phosphorylation of MAPK. The differential effects of these two thiols are not due to their redox states as oxidized Hcy ( Hcy thiolactone) enhanced MAPK phosphorylation. The effect of alpha LA appears to be serum-dependent because Hcy or alpha LA treatment of serum-deprived cells activated MAPK phosphorylation. Thus, alpha LA and Hcy can either induce common signal transduction pathways or differentially modulate MAPK phosphorylation, depending on the state of the cell. This relationship may be important to understand how some biothiols are associated with pathogenic events while others offer potential as therapeutic agents. Antiox. Redox Signal. 1, 123-128.