Isopropyl unoprostone increases the activities of matrix metalloproteinases in cultured monkey ciliary muscle cells
Isopropyl unoprostone increases the activities of matrix metalloproteinases in cultured monkey ciliary muscle cells
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DOI：
10.1097/00061198-200108000-00005
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发表时间：
2001-08-01
影响因子：
2
通讯作者：
Tsukahara, S
中科院分区：
文献类型：
--
作者：
Kashiwagi, K;Jin, M;Tsukahara, S
目的：前列腺素F-2α相关抗青光眼化合物异丙基乌诺前列酮（红色简称乌诺前列酮）降低眼压的机制尚不清楚。另一种前列腺素 F-2 α 相关化合物，拉坦前列素。影响睫状肌基质金属蛋白酶的活性。乌诺前列酮滴眼液在眼内代谢为氧化代谢物，主要是M1和M2。本研究的目的是探讨乌诺前列酮 M1 和 M2 的眼内代谢物是否会改变培养的猴睫状肌细胞中的金属蛋白酶活性。 材料和方法：猴睫状肌细胞和小梁网细胞在单层细胞培养物中分别生长至汇合。将M1（10 nM、100 nM或1 muM）、M2（10 nM、100 nM或1 muM）、100 nM前列腺素F-2α或载体溶液添加至每种培养基中48小时。然后对培养基进行分析，通过底物酶谱法定量测量金属蛋白酶活性。 结果：与载体对照、M1、M2 相比。和前列腺素F-2α以剂量依赖性方式显着增加培养的睫状肌细胞中的金属蛋白酶-2活性，但不影响培养的小梁网细胞中的金属蛋白酶-2活性。所有实验的前列腺素均略微增加了睫状肌细胞中金属蛋白酶9的活性，但这些变化并不显着。结论：目前的结果表明，乌诺前列酮影响睫状肌细胞外基质的代谢，睫状肌细胞外基质的重塑可能是乌诺前列酮滴眼液降低眼压的可能机制。
Purpose: The mechanism by which the prostaglandin F-2 alpha-related antiglaucoma compound isopropyl unoprostone (refer-red to as unoprostone) reduces intraocular pressure is largely unknown. Another prostaglandin F-2 alpha-related compound, latanoprost. influences the activities of matrix metalloproteinases in ciliary muscle. Unoprostone ophthalmic solution is metabolized to oxidized metabolites, mainly M1 and M2, in the eye. The aim of this study was to investigate whether intraocular metabolites of unoprostone, M1 and M2, change the metalloproteinase activity in cultured monkey ciliary muscle cells.Materials and Methods: Monkey ciliary muscle cells and trabecular meshwork cells were grown separately to confluence in monolayer cell cultures. M1 (10 nM, 100 nM, or 1 muM), M2 (10 nM, 100 nM, or 1 muM) 100 nM prostaglandin F-2 alpha, or vehicle solutions were added to each culture medium for 48 hours. The media were then assayed to measure metalloproteinase activities quantitatively by means of substrate zymography.Results: Compared with the vehicle controls, M1, M2. and prostaglandin F-2 alpha Significantly increased the metalloproteinase-2 activity in cultured ciliary muscle cells in a dose-dependent manner, but did not affect the metalloproteinase-2 activity in cultured trabecular meshwork cells. All experimented prostaglandins slightly increased metalloproteinase-9 activity in ciliary muscle cells, although these changes were not significant.Conclusions: The current results show that unoprostone influences the metabolism of the extracellular matrix in the ciliary muscle and that remodeling of the extracellular matrix in the ciliary muscle may be a possible mechanism by which unoprostone ophthalmic solution reduces intraocular pressure.