The protective role of peroxidase 6 against peroxidative stress in pulmonary microvascular endothelial cells includes its ability to repair peroxidized cell membranes (693.4)

Abstract

Peroxiredoxin 6 (Prdx6) is known to play a critical role in antioxidant defense of lung and other organs. Our aim in this research was to investigate whether this protective function of Prdx6 includes an ability to repair peroxidized cell membranes. Mouse pulmonary microvascular endothelial cells (PMVECs) were treated with tert‐butyl hydroperoxide (tBOOH) and lipid peroxidation was evaluated by measurement of thiobarbituric acid reactive substances (TBARS). PMVECs from Pxdx6 null mice showed much higher levels of lipid peroxidation upon tBOOH (50‐300 μM) exposure compared with wild‐type (WT).To determine whether Prdx6 is necessary for repair, PMVECs were treated with tBOOH (300 μM) for 24 h and then evaluated at 0,2,4 and 6 h after removal of the oxidant. TBARS in WT PMVECs returned to the levels of unexposed control level in 2 h. On the contrary, TBARS in PMVECs from Pxdx6 null mice were unchanged from their elevated levels during 6 h observation after cessation of tBOOH exposure. These results indicate that Prdx6 plays a critical role in protecting PMVECs against peroxidative stress both by preventing lipid peroxidation during the oxidant exposure and through its ability to repair peroxidized cell membrane during the subsequent recovery period following removal of the oxidative stress.Grant Funding Source: Supported by 5T32HL007748‐20, RO1‐HL 102011, and PO1‐HL19737