The Role of p38MAPK-eNOS-NO Signaling Pathway in the Protection Mechanisms of Apoptosis of Endothelial Cells
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1.Endocrinology Department, ;2.Central Laboratory, ;3.Nuclear Medicine Department, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China)

Clc Number:

R363

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    Abstract:

    Aim To investigate whether p38MAPK signaling pathway is involved in the protective mechanism of glucagon like peptide-1 (GLP-1) on endothelial cell damage induced by advanced glycation endproducts (AGE). Methods The experiment was divided into control group, AGE group, GLP-1 group, AGE+GLP-1 group, AGE+SB203580 group, AGE+GLP-1+SB203580 group, AGE+GLP-1+L-NAME group. Expression of p-p38MAPK/p38MAPK, phospho endothelial nitric oxide synthase/endothelial nitric oxide synthase (p-eNOS/eNOS) protein were examined by Western blot. Nitric oxide (NO) generation was detected by NO detection kit. Reactive oxygen species (ROS) generation was examined by fluorescent probe technique. The apoptosis rate was tested by Annexin V/PI flow cytometry. Results Compared with AGE group, GLP-1 inhibited the expression of p-p38MAPK protein(P=0.000). Compared with control group, after adding GLP-1 or p38MAPK inhibitor (SB203580), the expression of eNOS protein inhibited and ROS generation induced by AGE was significantly increased(P=0.004)or decreased(P=0.000). After adding GLP-1, the increased apoptosis rate induced by AGE was inhibited significantly(P=0.000). While after adding L-NAME, the anti-apoptosis effect was significantly weakened(P=0.002). After adding GLP-1, NO generation increased significantly(P=0.000) compared with AGE group. While after adding L-NAME, NO generation decreased significantly(P=0.011). Conclusion GLP-1 can inhibit the oxidative damage of vascular endothelial cells by inhibiting the activation of p38MAPK signaling pathway, and increase the expression of eNOS protein to increase NO generation and antagonize apoptosis induced by AGE.

    Reference
    [1] Singh VP, Bali A, Singh N, et al.Advanced glycation end products and diabetic complications.Korean J Physiol Pharmacol, 4,8(1):1-14.
    [2] 孙慧琳, 湛奕, 刘珍珍, 等.人脐静脉内皮细胞的原代培养及鉴定.广东医学, 2,3(6):744-746.
    [3] 孙慧琳, 刘珍珍, 李琼, 等.胰高血糖素样肽-1对糖基化终末产物诱导的血管内皮细胞损伤的保护作用.实用医学杂志, 3,4(3):496-498.
    [4] Fukami K, Yamagishi S, Okuda S.Role of AGEs-RAGE system in cardiovascular disease.Curr Pharm Des, 4,0(14):2 395-402.
    [5] Hu H, Jiang H, Ren H, et al.AGEs and chronic subclinical inflammation in diabetes:disorders of immune system.Diabetes Metab Res Rev, 5,1(2):127-137.
    [6] Dharmalingam M.Efficacy and tolerability of GLP-1 agonists in patients with type 2 diabetes mellitus:an Indian perspective.Ther Adv Endocrinol Metab, 4,5(6):159-165.
    [7] Weinberg E, Maymon T, Weinreb M.AGEs induce caspase-mediated apoptosis of rat BMSCs via TNFalpha production and oxidative stress.J Mol Endocrinol, 4,2(1):67-76.
    [8] Xia N, Forstermann U, Li H.Resveratrol and endothelial nitric oxide.Molecules, 4,9(10):16 102-121.
    [9] Bir SC, Xiong Y, Kevil CG, et al.Emerging role of PKA/eNOS pathway in therapeutic angiogenesis for ischaemic tissue diseases.Cardiovasc Res, 2,5(1):7-18.
    [10] Erdogdu O, Nathanson D, Sjoholm A, et al.Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor.Mol Cell Endocrinol, 0,5(1-2):26-35.
    [11] Huang A, Yang YM, Yan C, et al.Altered MAPK signaling in progressive deterioration of endothelial function in diabetic mice.Diabetes, 2,1(12):3 181-188.
    [12] Ishibashi Y, Matsui T, Takeuchi M, et al.Sitagliptin augments protective effects of GLP-1 against advanced glycation end product receptor axis in endothelial cells.Horm Metab Res, 1,3(10):731-734.
    [13] 魏丹丹, 林旭红, 王慧超, 等.香草乙酮改善葡聚糖硫酸钠诱发溃疡性结肠炎小鼠的炎 症反应与NOXs-ROS-p38MAPK信号通路的关系.生理学报, 5,7(1):74-82.
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SUN Hui-Lin, HUANG Zhi-Qiu, ZENG Hai-Long, ZHANG Yi-Neng, LIU Yi-Ming. The Role of p38MAPK-eNOS-NO Signaling Pathway in the Protection Mechanisms of Apoptosis of Endothelial Cells[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2016,24(6):561-565.

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History
  • Received:October 30,2015
  • Revised:December 20,2015
  • Online: June 30,2016
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