title: New role of JAK2/STAT3 signaling in endothelial cell oxidative stress injury and protective effect of melatonin.
abstract: Previous studies have shown that the JAK2/STAT3 signaling pathway plays a regulatory role in cellular oxidative stress injury (OSI). In this study, we explored the role of the JAK2/STAT3 signaling pathway in hydrogen peroxide (H2O2)-induced OSI and the protective effect of melatonin against (H2O2)-induced injury in human umbilical vein endothelial cells (HUVECs). AG490 (a specific inhibitor of the JAK2/STAT3 signaling pathway) and JAK2 siRNA were used to manipulate JAK2/STAT3 activity, and the results showed that AG490 and JAK2 siRNA inhibited OSI and the levels of p-JAK2 and p-STAT3. HUVECs were then subjected to H2O2 in the absence or presence of melatonin, the main secretory product of the pineal gland. Melatonin conferred a protective effect against H2O2, which was evidenced by improvements in cell viability, adhesive ability and migratory ability, decreases in the apoptotic index and reactive oxygen species (ROS) production and several biochemical parameters in HUVECs. Immunofluorescence and Western blotting showed that H2O2 treatment increased the levels of p-JAK2, p-STAT3, Cytochrome c, Bax and Caspase3 and decreased the levels of Bcl2, whereas melatonin treatment partially reversed these effects. We, for the first time, demonstrate that the inhibition of the JAK2/STAT3 signaling pathway results in a protective effect against endothelial OSI. The protective effects of melatonin against OSI, at least partially, depend upon JAK2/STAT3 inhibition.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shanxi Province, China.
authors.forename: Weixun
authors.initials: W
authors.lastname: Duan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Yan
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Liang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
authors.forename: Zhenxiao
authors.initials: Z
authors.lastname: Jin
authors.forename: Dinghua
authors.initials: D
authors.lastname: Yi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D053614:Janus Kinase 2 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020011:Protective Agents; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053614:Janus Kinase 2; D053148:Caspase 3; D008550:Melatonin