PMID- 31524245 OWN - NLM STAT- MEDLINE DCOM- 20200204 LR - 20200204 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 20 IP - 3 DP - 2019 Sep TI - N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway. PG - 2945-2953 LID - 10.3892/mmr.2019.10526 [doi] AB - Lipopolysaccharide (LPS) can regulate the expression of apoptotic factors, including caspase‑3, Bcl‑2 and Bcl‑2‑associated X protein (Bax). Nitric oxide (NO) plays an important role in apoptosis. N‑acetyl cysteine (NAC) has been shown to exhibit antioxidant effects in vitro. However, the effects of NAC on LPS‑induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the associated mechanisms are not well characterized. The present study explored the effect of NAC on LPS‑induced apoptosis of HUVECs and determined the participation of the p38 mitogen‑activated protein kinase (MAPK) pathway in the process of apoptosis. Cell viability was assessed using the Cell Counting Kit‑8 (CCK‑8) assay. The expression of caspase‑3, Bax, Bcl‑2, phosphorylated (p)‑p38MAPK/total (t‑)p38MAPK and p‑endothelial e nitric oxide synthase (eNOS)/t‑eNOS proteins were determined by western blotting. The expression levels of caspase‑3, Bax and Bcl‑2 mRNA were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The rate of apoptosis was determined using flow cytometry. An NO detection kit (nitric reductase method) was used to determine NO concentration. The results of CCK‑8 and flow cytometric analyses showed that pretreatment of HUVECs with NAC or p38MAPK inhibitor (SB203580) attenuated LPS‑induced decrease in cell viability and increase in cell apoptosis. RT‑qPCR and western blotting showed that LPS promoted caspase‑3 and Bax expression, but inhibited that of Bcl‑2 in HUVECs; however, these effects were attenuated by pretreatment with NAC or SB203580. LPS stimulation significantly enhanced the expression of p‑p38MAPK protein and reduced the expression of p‑eNOS protein; however, these effects were attenuated by pretreatment with NAC or SB203580. NAC pretreatment attenuated LPS‑induced inhibition of NO synthesis, which was consistent with the effects of SB203580. The results demonstrated that NAC pretreatment alleviated LPS‑induced apoptosis and inhibition of NO production in HUVECs. Furthermore, these effects were proposed to be mediated via the p38MAPK signaling pathway. FAU - Xiong, Ting AU - Xiong T AD - Department of Prosthodontics, Hospital of Stomatology Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. FAU - Zhang, Zhenzhen AU - Zhang Z AD - Department of Prosthodontics, Hospital of Stomatology Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. FAU - Zheng, Rui AU - Zheng R AD - Department of Prosthodontics, Hospital of Stomatology Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. FAU - Huang, Jialin AU - Huang J AD - Department of Prosthodontics, Hospital of Stomatology Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. FAU - Guo, Ling AU - Guo L AD - Department of Prosthodontics, Hospital of Stomatology Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. LA - eng PT - Journal Article DEP - 20190725 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Biomarkers) RN - 0 (Lipopolysaccharides) RN - 31C4KY9ESH (Nitric Oxide) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*pharmacology MH - Apoptosis/*drug effects MH - Biomarkers MH - Cell Survival/drug effects MH - Human Umbilical Vein Endothelial Cells/*drug effects/*metabolism MH - Humans MH - Lipopolysaccharides/*pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Nitric Oxide/metabolism MH - Phosphorylation/drug effects EDAT- 2019/09/17 06:00 MHDA- 2020/02/06 06:00 CRDT- 2019/09/17 06:00 PHST- 2019/02/25 00:00 [received] PHST- 2019/07/05 00:00 [accepted] PHST- 2019/09/17 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2019/09/17 06:00 [entrez] AID - 10.3892/mmr.2019.10526 [doi] PST - ppublish SO - Mol Med Rep. 2019 Sep;20(3):2945-2953. doi: 10.3892/mmr.2019.10526. Epub 2019 Jul 25.