Exprimental Study Of Niacin-Induced Heme Oxygenase-1against Apoptosis In Endothelial Cells

Objective:We examined the ef ect of niacin on the upgrading of HO-1expression in human umbilical vein endothelial cells （HUVECs） underoxidative stress conditions, and further assessed whether the effect wasmediated by p38mitogen-activatedproteinkinase（MAPK）.Methods:Oxidative stress was induced by hydrogen peroxide（100mmol/L）. HUVECs were treated with di f erent concentrations （0,0.25,0.5and1.0mM） of niacin for various periods of time（2,4,6,12,24h）.For inhibitor experiments, HUVECs were pretreated with SB203580（10mmol/L）, a p38-mitogen-activated protein kinase inhibitor; PD98059（25mmol/L）, aERKs inhibitor; SP600125（10mmol/L）, a JNKs inhibitor orZnPPⅨ（10uM）, an HO-1activity inhibitor. Real-time Quantity polymerase chain reaction was used to detectHO-1mRNA expression. HO-1protein was measured by western blot analysis. AndHO-1activity need to be measured. TUNEL asssy was applied to assess HUVECsapoptosisResults:â‘ Treated with H₂O₂（100uM） for12h after administration of niacin（1mM）for2,4,6,12, and24h respectively, we found that HO-1mRNA and protein expressionin H₂O₂plus Niacin group increased time-dependently and was significantly higher thanH₂O₂group（P<0.05）. After treatment with niacin at0.25,0.5and1.0mM for24hrespectively, results showed that HO-1mRNA and protein expression in H₂O₂plusNiacin group increased concentration-dependently and was higher than H₂O₂group orcontrolled group（P<0.05）.â‘¡After treatment with niacin at1mM for2,4,6,12, and24h respectively, H₂O₂（100uM） was added into culturedcells.12h later, we found that HO-1activity inincreased time-dependently and was higher than H₂O₂group（P<0.01）. Then we treatedHUVECs with niacin at0.25,0.5and1.0mM for24h respectively, HO-1activity in H₂O₂plus Niacin group increased concentration-dependently and was higher thanH₂O₂groupor controlled group （P<0.01）.â‘¢Under the condition of oxidative stress induced by H₂O₂, treatment with SB203580,inhibitor of p38-MAPKs, at10uM could inhibit the HO-1expression in HUVECsinduced by niacin（P<0.01） while PD98059（25uM）, inhibitor of ERKs, andSP600125(10uM, inhibitor of JNKs, have no similar effect.â‘£Apoptosis index of endothelial cells in H₂O₂group was higher than controlledgroup（P<0.01） and H₂O₂plus Niacin group（P<0.01）. Pretreatment withZnPPIX（10uM）, inhibitor of HO-1, could partly reverse these effects.Conclusion:â‘ Under the condition of oxidative stress, niacin could increase theexpression and activity of HO-1in HUVECs time-and concentration-dependentlythrough p38-MAPKs pathway.â‘¡Partly associated with HO-1, niacin could inhibit theapoptosis of HUVECs induced by oxidative stress.