PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells.
PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells.
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DOI：
10.1080/10715760903062887
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发表时间：
2009-09
影响因子：
3.3
通讯作者：
Singh DP
中科院分区：
文献类型：
--
作者：
Fatma N;Kubo E;Toris CB;Stamer WD;Camras CB;Singh DP
氧化应激和tgf β诱导的细胞和组织紊乱与细胞/组织病理生理的发生和发展有关。利用正常和青光眼患者的人小梁网（TM）细胞，我们证明了抗氧化剂过氧化物还蛋白（PRDX） 6通过优化ROS和TGFβ水平来抵消氧化应激对TM细胞的有害影响。对青光眼TM细胞的分析显示PRDX6 mRNA和蛋白的表达降低。生化分析显示ROS水平升高，TGFβs水平升高，这些细胞表达细胞外基质（ECM）和tsp1蛋白升高，MMP2降低；与青光眼病理生理相关的条件。暴露于tgf - βs/ROS的非青光眼TM细胞表现出与青光眼细胞相似的特征。PRDX6可逆转诱导的异常。本研究为氧化应激诱导的TM异常可能与PRDX6表达降低有关提供了证据，为以抗氧化剂为基础的青光眼治疗提供了基础。
Oxidative stress and TGFβ-induced disturbance of cells and tissues are implicated in initiation and progression of pathophysiology of cells/tissues. Using primary human Trabecular Meshwork (TM) cells from normal and glaucomatous subjects, we demonstrated that peroxiredoxin (PRDX) 6, an antioxidant, offsets the deleterious effects of oxidative stress on TM cells by optimizing ROS and TGFβ levels. An analysis of glaucomatous TM cells revealed a reduced expression of PRDX6 mRNA and protein. Biochemical assays disclosed enhanced levels of ROS, as well as high levels of TGFβs, and these cells expressed elevated extracellular matrix (ECM) andTsp1 proteins with reduced MMP2; conditions implicated in the pathophysiology of glaucoma. Nonglaucomatous TM cells exposed to TGFβs/ROS showed similar features as in glaucomatous cells. The abnormalities induced were reversed by delivery of PRDX6. The data provide evidence that oxidative stress-induced abnormality in TM may be related to reduced PRDX6 expression, and provide a foundation for antioxidant-based therapeutics for treating glaucoma.