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.
Wood
J L
JL
Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School of University College London, UK.
Graham
A
A
D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D019327:Copper Sulfate / Q000378:metabolism; D017077:Culture Media, Conditioned; D003553:Cystine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005290:Ferric Compounds / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002614:Chelating Agents; D017077:Culture Media, Conditioned; D005290:Ferric Compounds; D005296:Ferrous Compounds; D008670:Metals; D010618:Phenanthrolines; D013438:Sulfhydryl Compounds; D013481:Superoxides; C017049:bathophenanthroline disulfonic acid; D003553:Cystine; C028559:bathocuproine sulfonate; D003300:Copper; D007501:Iron; D011493:Protein Kinase C; D019327:Copper Sulfate; D013755:Tetradecanoylphorbol Acetate