Amyloid beta peptide (1-42)-mediated antioxidant imbalance is associated with activation of protein kinase C in red blood cells.
Glycolysis and pentose phosphate pathway (PPP) in red blood cell (RBC) are modulated by the cell oxygenation state. This metabolic modulation is connected to variations in intracellular nicotinamide adenine dinucleotide phosphate-reduced form (NADPH) and adenosine triphosphate (ATP) levels as a function of the oxygenation state of the cell, and, consequently, it should have physiologic relevance. In the present study, we analysed the effects of amyloid beta peptide (1-42) (Abeta) on RBC metabolism and its relationship with the activity of protein kinase C (PKC). Our results showed that metabolic response to Abeta depended on the degree of cell oxygenation. In particular, under high O2 pressure, in Abeta-treated RBC, glucose metabolized through PPP approached that metabolized by RBC under low O2 pressure, differently to that observed in untreated cells. The effect of Abeta on RBC metabolism was paralleled by increase in PKC enzyme activity, but cytosolic Ca2+ concentration does not seem to be involved in this mechanism. Incubation of Abeta-treated RBC with a specific inhibitor of PKC partially restores PPP flux. A possible rationalization of the different metabolic behaviours shown by RBC following Abeta treatment is proposed. It takes into account the known post-translational modifications to cytoskeleton proteins induced by PKC. The reduction in PPP flux may lead to a weakened defence system of antioxidant reserve in RBC, becoming a source of reactive species, and, consequently, its typical, structural and functional features are lost. Therefore, oxidative stress may outflow from the RBC and trigger damage events in adjacent cells and tissue, thus contributing to vascular damage.
Biochemistry and Clinical Biochemistry Institute, School of Medicine, Catholic University, Rome, Italy.
Cristiana
C
Carelli-Alinovi
Biochemistry and Clinical Biochemistry Institute, School of Medicine, Catholic University, Rome, Italy.|Istituto di Chimica del Riconoscimento Molecolare (ICRM), National Research Council (CNR), Rome, Italy.
Bruno
B
Giardina
Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino, FR, Italy.
Francesco
F
Misiti
D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D005947:Glucose
amyloid beta peptide; oxidative stress; pentose phosphate pathway; protein kinase C; red blood cell