High uric acid aggravates apoptosis of lung epithelial cells induced by cigarette smoke extract through downregulating PRDX2 in chronic obstructive pulmonary disease.

Abstract

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). Cigarette smoke heightens the elevation of reactive oxygen species (ROS) and thus leads to apoptosis. Hyperuricemia has been considered as a risk factor for COPD. However, the underlying mechanism for this aggravating effect remains unclear. The current study sought to examine the role of high uric acid (HUA) in COPD using cigarette smoke extract (CSE) exposed murine lung epithelial (MLE-12) cells. Our data showed that CSE induced the increase of ROS, mitochondrial dynamics disorder, and apoptosis, while HUA treatment aggravated the effects of CSE. Further studies suggested that HUA decreased the expression of antioxidant enzyme-peroxiredoxin-2 (PRDX2). Overexpression of PRDX2 inhibited excessive ROS generation, mitochondrial dynamics disorder, and apoptosis induced by HUA. Knockdown of PRDX2 by small interfering RNA (siRNA) promoted ROS generation, mitochondrial dynamics disorder, and apoptosis in MLE-12 cells treated with HUA. However, antioxidant N-acetylcysteine (NAC) reversed the effects of PRDX2-siRNA on MLE-12 cells. In conclusion, HUA aggravated CSE-induced cellular ROS levels and led to ROS-dependent mitochondrial dynamics disorder and apoptosis in MLE-12 cells through downregulating PRDX2.