Some biologically derived thiol-containing compounds have potential
for health benefits whereas others elicit biochemical events
leading to pathogenesis. Effects of two biothiols, a-lipoic
acid (aLA), a therapeutic antioxidant, and homocysteine (Hcy),
a risk factor for age-associated cardiovascular disease, on
cell signaling events involving p44 and p42 MAP kinases (p44/42
MAPK) were evaluated in cell culture. Treatment of serum-deprived
NIH/3T3 cells with Hcy (20 µM) resulted in the activation
of p44/42 MAPK as determined by Western blot analysis using
the phospho-specific p44/42 MAPK antibody. p44/42 MAPK phosphorylation
was rapid and transient with maximal activation occurring at
10-30 min. Transient activation of p44/42 MAPK was also observed
in response to treatment of serum-deprived cells with
LA. In
cells grown in serum, serum-dependent p44/42 MAPK phosphorylation
was transiently enhanced by Hcy or Hcy thiolactone, but inhibited
by
LA. Thus,
LA and Hcy differentially influence signal transduction
events depending on the state of cells. These observations may
be important in understanding how some biothiols are associated
with pathogenic events while others have potential as therapeutic
agents.
