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Chai J, Luo L, Hou F, et al. Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages. PLoS One. 2016;11(9):e0163634doi: 10.1371/journal.pone.0163634.
Chai, J., Luo, L., Hou, F., Fan, X., Yu, J., Ma, W., Tang, W., Yang, X., Zhu, J., Kang, W., Yan, J., & Liang, H. (2016). Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages. PloS one, 11(9), e0163634. https://doi.org/10.1371/journal.pone.0163634
Chai, Jianshen, et al. "Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages." PloS one vol. 11,9 (2016): e0163634. doi: https://doi.org/10.1371/journal.pone.0163634
Chai J, Luo L, Hou F, Fan X, Yu J, Ma W, Tang W, Yang X, Zhu J, Kang W, Yan J, Liang H. Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages. PLoS One. 2016 Sep 29;11(9):e0163634. doi: 10.1371/journal.pone.0163634. eCollection 2016. PMID: 27685463; PMCID: PMC5042521.
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PLoS One. 2016 Sep 29;11(9):e0163634. doi: 10.1371/journal.pone.0163634. eCollection 2016.

Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages.

PloS one

Jianshen Chai, Li Luo, Fengyan Hou, Xia Fan, Jing Yu, Wei Ma, Wangqi Tang, Xue Yang, Junyu Zhu, Wenyuan Kang, Jun Yan, Huaping Liang

Affiliations

  1. State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
  2. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.

PMID: 27685463 PMCID: PMC5042521 DOI: 10.1371/journal.pone.0163634

Abstract

Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS) and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS). We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that α2-adrenoceptor, I1-imidazoline receptor or I2-imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation.

Conflict of interest statement

The authors have declared that no competing interests exist.

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