Oxidised low density lipoprotein causes human macrophage cell death through oxidant generation and inhibition of key catabolic enzymes

• Published in: International Journal of Biochemistry and Cell Biology
• Main Author: Katouah H.; Chen A.; Othman I.; Gieseg S.P.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2015
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84940866610&doi=10.1016%2fj.biocel.2015.08.001&partnerID=40&md5=267b6e1a3195735ce995c7f5a8940269

Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3 h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death. © 2015 Elsevier Ltd.