Ulinastatin attenuates LPS-induced human endothelial cells oxidative damage through suppressing JNK/c-Jun signaling pathway.
Lipopolysaccharide (LPS)-induced oxidative stress is a main feature observed in the sepsis by increasing endothelial oxidative damage. Many studies have demonstrated that Ulinastatin (UTI) can inhibit pro-inflammatory proteases, decrease inflammatory cytokine levels and suppress oxidative stress. However, the potential molecular mechanism underlying UTI which exerts its antioxidant effect is not well understood. In this study, we aimed to investigate the effects of UTI on the LPS-induced oxidative stress and the underlying mechanisms using human umbilical vein endothelial cells (HUVECs). After oxidative stress induced By LPS in HUVECs, the cell viability and reactive oxygen species (ROS) in cytoplasm were measured. In addition, superoxide dismutase (SOD) and malondialdehyde (MDA) were examined. We found that LPS resulted in a profound elevation of ROS production and MDA levels. The decrease in Cu/Zn-SOD protein and increased in Mn-SOD protein were observed in a time- and dose-dependent manner. These responses were suppressed by an addition of UTI. The increase in c-Jun N-terminal kinases (JNK) phosphorylation by LPS in HUVECs was markedly blocked by UTI or JNK inhibitor SP600125. Our results suggest that UTI exerts its anti-oxidant effects by decreasing overproduction of ROS induced by LPS via suppressing JNK/c-Jun phosphorylation. Therefore UTI may play a protective role in vascular endothelial injury induced by oxidative stress such as sepsis. This study may provide insight into a possible molecular mechanism by which Ulinastatin inhibits LPS-induced oxidative stress.
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Chunping
C
Li
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Dandan
D
Ma
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Man
M
Chen
Department of Critical-Care Medicine, Affiliated Hospital of Weifang Medical University, Weifang, 261000, China.
Linlin
L
Zhang
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Lin
L
Zhang
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Jicheng
J
Zhang
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Xin
X
Qu
Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. Electronic address: wcteicu@126.com.
Chunting
C
Wang
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006023:Glycoproteins / Q000008:administration & dosage*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014361:Trypsin Inhibitors / Q000008:administration & dosage
D006023:Glycoproteins; D008070:Lipopolysaccharides; D014361:Trypsin Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C028665:urinastatin
HUVECs; JNK/c-Jun signaling pathways; Lipopolysaccharide; Oxidative stress; ROS; Ulinastatin