Homocysteine and alpha-lipoic acid regulate p44/42 MAP kinase phosphorylation in NIH/3T3 cells.
Biological thiols can regulate cell signal transduction. The effects of two biothiols, homocysteine (Hcy), a risk factor for cardiovascular disease, and alpha-lipoic acid (alphaLA), 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 microM Hcy for 0-60 min resulted in a transient enhancement of MAPK phosphorylation. In contrast, 20 microM alphaLA 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 alphaLA appears to be serum-dependent because Hcy or alphaLA treatment of serum-deprived cells activated MAPK phosphorylation. Thus, alphaLA 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.
Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
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SS
Shi
R M
RM
Day
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AD
Halpner
J B
JB
Blumberg
Y J
YJ
Suzuki
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor; D015398:Signal Transduction; D008063:Thioctic Acid / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D006710:Homocysteine; D008063:Thioctic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)