Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery.
Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery.
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DOI：
10.1007/s00109-016-1502-4
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Michael Wormstone I
中科院分区：
文献类型：
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作者：
Liu H;Smith AJ;Ball SS;Bao Y;Bowater RP;Wang N;Michael Wormstone I
后囊混浊(PCO)通常发生在白内障手术后，是一种伤口愈合反应，最终可能导致继发性视力丧失。需要改进对这个问题的管理。据报道，异硫氰酸酯萝卜硫醚(SFN)具有细胞保护和细胞毒作用，后者可用于治疗/预防PCO。在人晶状体囊袋模型中，SFN浓度为10μM及以上时，伤口愈合明显受损。人类晶状体细胞系FHL124也出现了类似的反应模式。SFN处理促进了内质网应激基因的表达，这也与蛋白质的表达相对应。通过微管相关蛋白1A/1B轻链3(LC3)-II水平的升高和自噬小泡的检测，观察到SFN反应中有自噬的证据。这种反应被已有的自噬抑制剂氯喹和3-MA干扰。SFN可促进MAPK信号转导，用U0126抑制ERK激活可阻止SFN诱导的LC3-II升高和囊泡形成。SFN还显著增加了活性氧的水平。综上所述，我们的研究结果表明，SFN能够抑制晶状体细胞的生长和活力，因此可以作为一种潜在的后囊混浊的治疗剂。SFN降低晶状体上皮细胞的生长、迁移和活性。SFN可促进晶状体细胞内质网应激和自噬。SFN促进MAPK信号转导，抑制MEK可抑制SFN诱导的自噬。ROS的产生可能促进了晶状体细胞的内质网应激和自噬。SFN可能有助于预防白内障术后后囊混浊。
Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyanate, sulforaphane (SFN), is reported to exert cytoprotective and cytotoxic actions, and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10 μM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of endoplasmic reticulum (ER) stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased microtubule-associated protein 1A/1B-light chain 3 (LC3)-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling, and inhibition of ERK activation using U0126 prevented SFN-induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO. SFN reduces lens epithelial cell growth, migration, and viability. SFN can promote ER stress and autophagy in lens cells. SFN promotes MAPK signaling, and inhibition of MEK can suppress SFN-induced autophagy. ER stress and autophagy in lens cells are likely promoted by ROS production. SFN may help prevent posterior capsule opacification after cataract surgery.