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Cytosolic phospholipase A2-α participates in lipid body formation and PGE2 release in human neutrophils stimulated with an L-amino acid oxidase from Calloselasma rhodostoma venom.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-07-03 , DOI: 10.1038/s41598-020-67345-3
Mauro Valentino Paloschi 1, 2 , Jéssica Amaral Lopes 1, 2 , Charles Nunes Boeno 1, 2 , Milena Daniela Souza Silva 1, 2 , Jaína Rodrigues Evangelista 1 , Adriana Silva Pontes 1, 2 , Sulamita da Silva Setúbal 1 , Cristina Matiele Alves Rego 1 , Neriane Monteiro Néry 1 , Alex Augusto Ferreira E Ferreira 1, 2 , Weverson Luciano Pires 1 , Kátia Paula Felipin 2, 3 , Gabriel Eduardo Melim Ferreira 2, 3 , Patrícia Torres Bozza 4 , Juliana Pavan Zuliani 1, 2, 5
Affiliation  

Cr-LAAO, an l-amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, has been demonstrated as a potent stimulus for neutrophil activation and inflammatory mediator production. However, the mechanisms involved in Cr-LAAO induced neutrophil activation has not been well characterized. Here we investigated the mechanisms involved in Cr-LAAO-induced lipid body (also known as lipid droplet) biogenesis and eicosanoid formation in human neutrophils. Using microarray analysis, we show for the first time that Cr-LAAO plays a role in the up-regulation of the expression of genes involved in lipid signalling and metabolism. Those include different members of phospholipase A2, mostly cytosolic phospholipase A2-α (cPLA2-α); and enzymes involved in prostaglandin synthesis including cyclooxygenases 2 (COX-2), and prostaglandin E synthase (PTGES). In addition, genes involved in lipid droplet formation, including perilipin 2 and 3 (PLIN 2 and 3) and diacylglycerol acyltransferase 1 (DGAT1), were also upregulated. Furthermore, increased phosphorylation of cPLA2-α, lipid droplet biogenesis and PGE2 synthesis were observed in human neutrophils stimulated with Cr-LAAO. Treatment with cPLA2-α inhibitor (CAY10650) or DGAT-1 inhibitor (A922500) suppressed lipid droplets formation and PGE2 secretion. In conclusion, we demonstrate for the first time the effects of Cr-LAAO to regulate neutrophil lipid metabolism and signalling.



中文翻译:

胞质磷脂酶A2-α参与人中性粒细胞中脂质体的形成和PGE2的释放,该中性粒细胞被来自红腹膜假单胞菌毒液的L-氨基酸氧化酶刺激。

Cr-LAAO是一种从卡洛斯拉丝红假单胞菌蛇毒中分离的1-氨基酸氧化酶,已被证明是一种有效的刺激中性粒细胞活化和炎症介质产生的方法。但是,Cr-LAAO诱导的中性粒细胞活化所涉及的机制尚未得到很好的表征。在这里,我们调查了人类中性粒细胞中Cr-LAAO诱导的脂质体(也称为脂质滴)生物发生和类花生酸形成的机制。使用微阵列分析,我们首次表明Cr-LAAO在上调参与脂质信号传导和代谢的基因表达中发挥作用。这些包括磷脂酶A 2的不同成员主要是胞质磷脂酶A 2- α(cPLA 2-α); 以及与前列腺素合成有关的酶,包括环加氧酶2(COX-2)和前列腺素E合酶(PTGES)。此外,与脂质滴形成有关的基因,包括外周血脂蛋白2和3(PLIN 2和3)和二酰基甘油酰基转移酶1(DGAT1)也被上调。此外,在用Cr-LAAO刺激的人中性粒细胞中观察到了cPLA 2- α的磷酸化增加,脂质液滴的生物发生和PGE 2合成。用cPLA 2- α抑制剂(CAY10650)或DGAT-1抑制剂(A922500)处理可抑制脂质液滴形成和PGE 2分泌。总之,我们首次证明了Cr-LAAO调节中性粒细胞脂质代谢和信号转导的作用。

更新日期:2020-07-03
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