Savion Naphtali, Dahamshi Samia, Morein Milana, Kotev-Emeth Shlomo
Goldschleger Eye Research Institute and Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 61390, Israel.
Antioxidants (Basel). 2019 Jan 16;8(1):25. doi: 10.3390/antiox8010025.
The capacity of -Allylmercapto--acetylcysteine (ASSNAC) to protect human retinal pigment epithelial (RPE) cells (line ARPE-19) and porcine lenses from oxidative stress was studied. Confluent ARPE-19 cultures were incubated with ASSNAC or -acetyl-cysteine (NAC) followed by exposure to oxidants and glutathione level and cell survival were determined. Porcine lenses were incubated with ASSNAC and then exposed to H₂O₂ followed by lens opacity measurement and determination of glutathione (reduced (GSH) and oxidized (GSSG)) in isolated lens adhering epithelial cells (lens capsule) and fiber cells consisting the lens cortex and nucleus (lens core). In ARPE-19 cultures, ASSNAC (0.2 mM; 24 h) increased glutathione level by 2⁻2.5-fold with significantly higher increase in GSH compared to NAC treated cultures. Similarly, ex-vivo exposure of lenses to ASSNAC (1 mM) significantly reduced the GSSG level and prevented H₂O₂ (0.5 mM)-induced lens opacification. These results demonstrate that ASSNAC up-regulates glutathione level in RPE cells and protects them from oxidative stress-induced cell death as well as protects lenses from oxidative stress-induced opacity. Further validation of these results in animal models may suggest a potential use for ASSNAC as a protective therapy in retinal degenerative diseases as well as in attenuation of oxidative stress-induced lens opacity.
研究了β-烯丙基巯基-β-乙酰半胱氨酸（ASSNAC）保护人视网膜色素上皮（RPE）细胞（ARPE-19细胞系）和猪晶状体免受氧化应激的能力。将汇合的ARPE-19细胞培养物与ASSNAC或N-乙酰半胱氨酸（NAC）一起孵育，然后暴露于氧化剂中，测定谷胱甘肽水平和细胞存活率。将猪晶状体与ASSNAC一起孵育，然后暴露于H₂O₂中，随后测量晶状体混浊度，并测定分离的晶状体黏附上皮细胞（晶状体囊）以及构成晶状体皮质和核（晶状体核心）的纤维细胞中的谷胱甘肽（还原型（GSH）和氧化型（GSSG））。在ARPE-19细胞培养物中，ASSNAC（0.2 mM；24小时）使谷胱甘肽水平提高了2至2.5倍，与NAC处理的培养物相比，GSH的增加明显更高。同样，离体将晶状体暴露于ASSNAC（1 mM）可显著降低GSSG水平，并防止H₂O₂（0.5 mM）诱导的晶状体混浊。这些结果表明，ASSNAC上调RPE细胞中的谷胱甘肽水平，保护它们免受氧化应激诱导的细胞死亡，同时保护晶状体免受氧化应激诱导的混浊。在动物模型中对这些结果的进一步验证可能表明ASSNAC在视网膜退行性疾病的保护性治疗以及减轻氧化应激诱导的晶状体混浊方面具有潜在用途。
