Reduction of transition metals by human (THP-1) monocytes is enhanced by activators of protein kinase C.

Macrophages oxidize low density lipoprotein (LDL) by enzymatic and non-enzymatic mechanisms; however, it is evident that macrophage reduction of transition metals can accelerate LDL oxidation in vitro, and possibly in vivo. Distinct cellular pathways contribute to this process, including trans-plasma membrane electron transport (TPMET), and production of free thiols or superoxide. Here, we explore the role of protein kinase C (PKC) in regulating transition metal reduction by each of these redox-active pathways, in human (THP-1) monocytes. We demonstrate that PKC agonists and/or inhibitors modulate reduction of transition metals by monocytes: both thiol-independent (direct) and thiol-dependent (indirect) pathways for transition metal reduction are enhanced by PKC activation, suggesting a potential strategy for therapeutic intervention.