Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H rhodopsin mutation.
Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H rhodopsin mutation.
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DOI：
10.1371/journal.pone.0021193
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ayyagari R
中科院分区：
文献类型：
--
作者：
Vasireddy V;Chavali VR;Joseph VT;Kadam R;Lin JH;Jamison JA;Kompella UB;Reddy GB;Ayyagari R
视紫红质基因的P23H突变导致视紫红质错误折叠，运输改变和不溶性聚集体的形成，导致光受体变性和常染色体显性视网膜色素变性（RP）。目前还没有有效的疗法来治疗这种疾病。增强蛋白质聚集体解离的化合物可能在开发治疗此类疾病的新方法中具有价值。姜黄素的抗蛋白聚集活性已有较早的报道。在这项研究中，我们提出用姜黄素处理表达突变视紫红质的COS-7细胞导致突变蛋白聚集体的解离并减少内质网应激。此外，我们证明姜黄素对p23h -视紫红质转基因大鼠的处理改善了视网膜形态、生理、基因表达和视紫红质定位。我们的研究结果表明，补充姜黄素可以改善p23h -视紫红质转基因大鼠的视网膜结构和功能。这些数据也提示姜黄素可能作为一种潜在的治疗剂用于治疗由P23H视紫红质突变引起的RP和其他由蛋白质运输缺陷引起的退行性疾病。
The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP). There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects.
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