Karthikeyan Bose, Arun Arumugaperumal, Harini Lakshminarasimhan, Sundar Krishnan, Kathiresan Thandavarayan
Department of Biotechnology, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.
International Research Centre, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.
Biol Trace Elem Res. 2016 Apr;170(2):390-400. doi: 10.1007/s12011-015-0493-2. Epub 2015 Sep 2.
Age-related macular degeneration (AMD) is the leading cause for irreversible visual impairment affecting 30-50 million individuals every year. Oxidative stress and endoplasmic reticulum stress have been identified as crucial factors for the pathogenesis of AMD. Current treatments do not focus on underlying stimuli responsible for the disease like AMD. Zinc is an important trace metal in retina and its deficiency leads to AMD. Recent studies on zinc sulphide nanoparticles (ZnS-NPs) are gaining attention in the field of physical and biological research. In this present study, in investigating the role of ZnS-NPs on hydrogen peroxide and thapsigargin-treated primary mice retinal pigment epithelial (MRPE) cells, we synthesized ZnS-NPs and characterized using atomic force microscope (AFM) and SEM-EDX. The ZnS-NPs abrogate the primary MRPE cell death through inhibition of oxidative stress-induced reactive oxygen species production and cell permeability. Oxidant molecules hydrogen peroxide and thapsigargin alter unfolded protein response such as glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP) expressions, whereas ZnS-NPs-pre-treated primary MRPE cells downregulated the overexpression of such proteins. The expressions of apoptotic proteins caspase 12 and cleaved caspase 9 and caspase 3 were also significantly controlled in ZnS-NPs-treated primary MRPE cells when comparing with thapsigargin- and hydrogen peroxide-treated cells. From these results, ZnS-NPs stabilize reactive oxygen species elevation, when subjected to hydrogen peroxide- and thapsigargin-mediated oxidant injury and helps in maintaining normal homeostasis through regulating endoplasmic reticulum (ER) stress response proteins which is the lead cause for apoptosis-mediated pathogenesis of AMD.
年龄相关性黄斑变性（AMD）是导致不可逆视力损害的主要原因，每年影响3000万至5000万人。氧化应激和内质网应激已被确定为AMD发病机制的关键因素。目前的治疗方法并未针对AMD等导致该疾病的潜在刺激因素。锌是视网膜中的一种重要微量元素，其缺乏会导致AMD。最近关于硫化锌纳米颗粒（ZnS-NPs）的研究在物理和生物学研究领域受到关注。在本研究中，为了探究ZnS-NPs对过氧化氢和毒胡萝卜素处理的原代小鼠视网膜色素上皮（MRPE）细胞的作用，我们合成了ZnS-NPs，并使用原子力显微镜（AFM）和扫描电子显微镜-能谱仪（SEM-EDX）对其进行了表征。ZnS-NPs通过抑制氧化应激诱导的活性氧生成和细胞通透性，消除原代MRPE细胞死亡。氧化分子过氧化氢和毒胡萝卜素会改变未折叠蛋白反应，如葡萄糖调节蛋白78（GRP78）和C/EBP同源蛋白（CHOP）的表达，而经ZnS-NPs预处理的原代MRPE细胞下调了这些蛋白的过表达。与毒胡萝卜素和过氧化氢处理的细胞相比，在经ZnS-NPs处理的原代MRPE细胞中，凋亡蛋白半胱天冬酶12、裂解的半胱天冬酶9和半胱天冬酶3的表达也得到了显著控制。从这些结果来看，当受到过氧化氢和毒胡萝卜素介导的氧化损伤时，ZnS-NPs能稳定活性氧的升高，并通过调节内质网（ER）应激反应蛋白来帮助维持正常的内环境稳定，而内质网应激反应蛋白是AMD凋亡介导发病机制的主要原因。
