Figure 8.

A schematic diagram of the inhibition of proliferation by SO₂ and the pathways. PDGF-BB can promote VSMC proliferation by activating Erk/MAPK pathway after combining with its specific RTKs. The increasing cAMP concentration in VSMCs induces PKA activation, which can disturb Erk/MAPK signaling transduction by inhibiting c-Raf activation. SO₂ derivatives can suppress the activities of Erk1/2, MEK1/2 and c-Raf, which does not result from separate targeting interferences of SO₂ derivatives on the three molecules but from the inhibition of upstream signaling by SO₂ derivatives. SO₂ derivatives might enhance adenylyl cyclase activity to elevate cAMP production from ATP and then activate PKA signal to block c-Raf activation, which finally contributes to the suppression of PDGF-BB-induced VSMC proliferation by SO₂ derivatives