CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Biochimie. 2013 Apr;95(4):903-11. doi: 10.1016/j.biochi.2012.12.008. Epub 2012 Dec 21.
Numerous studies have reported the implication of calcium-independent phospholipase A2 (iPLA2) in various biological mechanisms. Most of these works have used in vitro models and only a few have been carried out in vivo on iPLA2(-/-) mice. The functions of iPLA2 have been investigated in vivo in the heart, brain, pancreatic islets, and liver, but not in the retina despite its very high content in phospholipids. Phospholipids in the retina are known to be involved in several various key mechanisms such as visual transduction, inflammation or apoptosis. In order to investigate the implication of iPLA2 in these processes, this work was aimed to build an in vivo model of iPLA2 activity inhibition. After testing the efficacy of different chemical inhibitors of iPLA2, we have validated the use of bromoenol lactone (BEL) in vitro and in vivo for inhibiting the activity of iPLA2. Under in vivo conditions, a dose of 6μg/g of body weight of BEL in mice displayed a 50%-inhibition of retinal iPLA2 activity 8-16h after intraperitoneal administration. Delivering the same dose twice a day to animals was successful in producing a similar inhibition that was stable over one week. In summary, this novel mouse model exhibits a significant inhibition of retinal iPLA2 activity. This model of chemical inhibition of iPLA2 will be useful in future studies focusing on iPLA2 functions in the retina.
许多研究已经报道了钙非依赖性磷脂酶 A2（iPLA2）在各种生物学机制中的作用。这些研究大多使用了体外模型，只有少数在 iPLA2（-/-）小鼠体内进行。iPLA2 的功能已在心脏、大脑、胰岛和肝脏等体内器官中进行了研究，但在视网膜中尚未进行研究，尽管视网膜中的磷脂含量非常高。已知视网膜中的磷脂参与了多种关键机制，如视觉转导、炎症或细胞凋亡。为了研究 iPLA2 在这些过程中的作用，本研究旨在建立 iPLA2 活性抑制的体内模型。在测试了不同 iPLA2 化学抑制剂的效果后，我们验证了溴烯醇内酯（BEL）在体外和体内抑制 iPLA2 活性的用途。在体内条件下，腹腔内给予小鼠 6μg/g 体重的 BEL 可在 8-16 小时内抑制视网膜 iPLA2 活性 50%。每天两次给动物给予相同剂量可成功产生稳定持续一周的类似抑制作用。总之，这种新型小鼠模型表现出对视网膜 iPLA2 活性的显著抑制。这种 iPLA2 的化学抑制模型将有助于未来研究 iPLA2 在视网膜中的功能。
