Cellular lipid peroxidation end-products induce apoptosis in human lens epithelial cells
Cellular lipid peroxidation end-products induce apoptosis in human lens epithelial cells
复制标题
DOI：
10.1016/s0891-5849(01)00810-3
复制
发表时间：
2002-02-15
影响因子：
7.4
通讯作者：
Ansari, NH
中科院分区：
文献类型：
--
作者：
Choudhary, S;Zhang, W;Ansari, NH
过氧化氢（H2 O2）是一种存在于老年人眼房水中的高浓度氧化剂，已知其对晶状体具有毒性-细胞凋亡是毒性事件之一。由于过氧化氢导致脂质过氧化反应，导致反应性终产物的形成，重要的是要调查是否脂质过氧化的终产物参与氧化诱导的细胞凋亡的透镜。4-羟基壬烯醛（HNE）是脂质过氧化的主要细胞毒性终产物，已被证明可介导多种细胞类型中氧化应激诱导的细胞死亡。体外研究表明，HNE在微摩尔浓度下可引起白内障，但其潜在机制尚未明确。在本研究中，我们已经证明，14，0，和脂质衍生的醛，HNE和4-羟基己烯醛（HHE），可以诱导剂量和时间依赖性的细胞活力的损失，并同时增加凋亡，涉及激活半胱天冬酶，如半胱天冬酶-1，-2，-3，和-8在培养的人透镜上皮细胞。有趣的是，我们观察到，Z-VAD，广泛的caspase抑制剂，赋予对H2 O2和HNE诱导的细胞凋亡的保护，这表明在这个凋亡系统中的caspase的参与。使用阳离子染料JC-1，在HNE和11，0，损伤5小时后评估早期凋亡变化。虽然HNE暴露导致类似于50%的细胞经历早期凋亡变化，但在此期间在处理的细胞中未观察到此类变化。此外，通过定量DNA片段化确定的细胞凋亡在HNE而不是H2 O2的更早的时间段是明显的。两者合计，结果表明，脂质过氧化终产物的凋亡潜力，并建议过氧化氢诱导的细胞凋亡可能介导的这些终产物在透镜上皮。(C)2002年爱思唯尔科学公司
Hydrogen peroxide (H2O2), an oxidant present in high concentrations in the aqueous humor of the elderly eyes, is known to impart toxicity to the lens-apoptosis being one of the toxic events. Since H2O2 causes lipid peroxidation leading to the formation of reactive end-products, it is important to investigate whether the end-products of lipid peroxidation are involved in the oxidation-induced apoptosis in the lens. 4-Hydroxynonenal (HNE), a major cytotoxic end product of lipid peroxidation, has been shown to mediate oxidative stress-induced cell death in many cell types. It has been shown that HNE is cataractogenic in micromolar concentrations in Vitro, however, the underlying mechanism is not yet clearly understood. In the present study we have demonstrated that 14,0, and the lipid derived aldehydes, HNE and 4-hydroxyhexenal (HHE), can induce dose- and time-dependent loss of cell viability and a simultaneous increase in apoptosis involving activation of caspases such as caspase-1, -2, -3, and -8 in the cultured human lens epithelial cells. Interestingly, we observed that Z-VAD, a broad range inhibitor of caspases, conferred protection against H2O2- and HNE-induced apoptosis, suggesting the involvement of caspases in this apoptotic system. Using the cationic dye JC-1, early apoptotic changes were assessed following 5 h of HNE and 11,0, insult. Though HNE exposure resulted in similar to 50% cells to undergo early apoptotic changes, no such changes were observed in treated cells during this period. Furthermore, apoptosis, as determined by quantifying the DNA fragmentation, was apparent at a much earlier time period by HNE as opposed to H2O2. Taken together, the results demonstrate the apoptotic potential of the lipid peroxidation end-products and suggest that H2O2-induced apoptosis may be mediated by these end-products in the lens epithelium. (C) 2002 Elsevier Science Inc.