N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

  • Authors:
    • Ting Xiong
    • Zhenzhen Zhang
    • Rui Zheng
    • Jialin Huang
    • Ling Guo
  • View Affiliations

  • Published online on: July 25, 2019     https://doi.org/10.3892/mmr.2019.10526
  • Pages: 2945-2953
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Abstract

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.

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APA
Xiong, T., Zhang, Z., Zheng, R., Huang , J., & Guo, L. (2019). N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway. Molecular Medicine Reports, 20, 2945-2953. https://doi.org/10.3892/mmr.2019.10526
MLA
Xiong, T., Zhang, Z., Zheng, R., Huang , J., Guo, L."N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway". Molecular Medicine Reports 20.3 (2019): 2945-2953.
Chicago
Xiong, T., Zhang, Z., Zheng, R., Huang , J., Guo, L."N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway". Molecular Medicine Reports 20, no. 3 (2019): 2945-2953. https://doi.org/10.3892/mmr.2019.10526