Phospholipase D1 activity is crucial for cytosolic phospholipase A2 –dependent prostaglandin E2 formation in murine osteoblastic MC3T3-E1 cells

IF 3

Prostaglandins, leukotrienes, and essential fatty acids Pub Date : 2023-10-30 DOI:10.1016/j.plefa.2023.102592

Hans Jörg Leis , Werner Windischhofer

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Abstract

In bone, prostaglandin E₂ (PGE₂) is highly osteogenic and formed by osteoblasts, a key modulatory event in the regulation of bone cell activity. MC3T3-E1 cells are widely used as an in vitro model of osteoblast function. It is still not clear which pathways contribute to the release of AA in these cells. In this study we have focussed on the contribution of phospholipase D (PLD) enzymes to osteoblastic PGE₂ formation after stimulation with endothelin-1 (ET-1). Using specific inhibitors of PLD1 and PLD2 we could show that PGE₂ formation was strictly dependent on PLD1 but not PLD2 activity and cytosolic phospholipase A₂ (cPLA₂) was activated by triggering through PLD1. We have identified diacyl glycerol (DAG) as a possible effector molecule which may serve as a triggering signal for PKC activation and subsequent cPLA₂ phosphorylation.

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在小鼠成骨细胞MC3T3-E1中，磷脂酶D1活性对于胞浆磷脂酶A2依赖性前列腺素E2的形成至关重要

在骨中，前列腺素E2 (PGE2)是高度成骨的，由成骨细胞形成，是骨细胞活性调节的关键调节事件。MC3T3-E1细胞被广泛用作成骨细胞功能的体外模型。目前尚不清楚哪些途径有助于这些细胞中AA的释放。在这项研究中，我们重点研究了磷脂酶D (PLD)酶在内皮素-1 (ET-1)刺激后对成骨细胞PGE2形成的贡献。使用特定的PLD1和PLD2抑制剂，我们可以发现PGE2的形成严格依赖于PLD1而不是PLD2的活性，细胞质磷脂酶A2 (cPLA2)通过PLD1触发激活。我们已经确定了二酰基甘油(DAG)作为可能的效应分子，它可能作为PKC激活和随后的cPLA2磷酸化的触发信号。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

64 days