FIG. 2. Crosstalk between cholesterol synthesis and iNOS gene expression.
Geranyl-pyrophosphate and farnesyl-pyrophosphate, generated by condensation of the mother carbon skeleton of isopendenyl pyrophosphate, modify membrane-coupled Rac and Ras, respectively, leading to their activation. Subsequently, MAP kinase pathways are employed to activate specific transcription factors, which then bind to their elements in the iNOS promoter and transactivate them. iNOS expression blockers may impede this pathway by interfering at specific points in the cholesterol synthesis pathway. Furthermore, activation of Rac also leads to activation of the NADPH complex. Thus, ROS is generated, which diffuses back into the cell to mediate its own signal is augmenting iNOS expression.