Lee Wonhwa, Kwak Soyoung, Lee Hyun-Shik, Na Dong Hee, Lee You-Mie, Bae Jong-Sup
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea; Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Biochem Biophys Res Commun. 2015 Apr 17;459(4):650-4. doi: 10.1016/j.bbrc.2015.02.165. Epub 2015 Mar 7.
Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial ischemia and reperfusion injury and inflammatory or oxidative responses. The expression level of secretory group IIA phospholipase A2 (sPLA2-IIA) is elevated in inflammatory diseases. Lipopolysaccharide (LPS) upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Here, EX4 was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mice. Pre-treatment of cells or mice with EX4 inhibited LPS-induced sPLA2-IIA expression and activity. Additionally, EX4 suppressed LPS-induced activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2. Therefore, these results show that EX4 inhibited LPS-induced expression of sPLA2-IIA by suppressing cPLA2 and ERK 1/2.
艾塞那肽-4（EX4）是一种胰高血糖素样肽-1受体激动剂，据报道可减轻心肌缺血再灌注损伤以及炎症或氧化反应。分泌型IIA组磷脂酶A2（sPLA2-IIA）的表达水平在炎症性疾病中会升高。脂多糖（LPS）可上调人脐静脉内皮细胞（HUVECs）中sPLA2-IIA的表达。在此，研究了EX4对HUVECs和小鼠中sPLA2-IIA表达及活性的影响。用EX4对细胞或小鼠进行预处理可抑制LPS诱导的sPLA2-IIA表达及活性。此外，EX4可抑制LPS诱导的胞质磷脂酶A2（cPLA2）和细胞外信号调节激酶（ERK）1/2的激活。因此，这些结果表明EX4通过抑制cPLA2和ERK 1/2来抑制LPS诱导的sPLA2-IIA表达。
