Nakajima T, Belusko P B, Walkup R D, Azuma M, Shearer T R
Research Laboratory of Ocular Sciences, Senju Pharmaceutical Co. Ltd, Kobe, Hyogo, Japan.
Exp Eye Res. 2006 May;82(5):874-8. doi: 10.1016/j.exer.2005.10.020. Epub 2005 Dec 20.
Selenite-overdose cataract in young rats may be caused by an initial insult to the lens epithelial cells. Our previous DNA array analysis revealed a significant increase in the expression of mRNA for early growth response protein-1 (Egr-1) in lens epithelial cells after injection of selenite. This suggested that up-regulation of Egr-1 mRNA may be involved in lens epithelial cell death. The purpose of the present experiment was to further clarify the involvement of Egr-1 in lens epithelial cell death induced by selenite. Rat lens epithelial explants were cultured with sodium selenite. Selenite caused epithelial explants to leak LDH into the medium. During LDH leakage, increased expression of mRNA for Egr-1 was observed by RT-PCR. To further test the involvement of Egr-1 in selenite-induced cell death, mouse lens epithelial cell line (alpha-TN4 cells) was treated with antisense oligonucleotide for Egr-1. Antisense oligonucleotide for Egr-1 significantly diminished expression of Egr-1 protein and leakage of LDH. These results suggested that increased activity of Egr-1 may be a factor in lens epithelial cell death induced by selenite.
幼鼠亚硒酸盐过量性白内障可能是由晶状体上皮细胞最初受到损伤所致。我们之前的DNA阵列分析显示，注射亚硒酸盐后，晶状体上皮细胞中早期生长反应蛋白-1（Egr-1）的mRNA表达显著增加。这表明Egr-1 mRNA的上调可能与晶状体上皮细胞死亡有关。本实验的目的是进一步阐明Egr-1在亚硒酸盐诱导的晶状体上皮细胞死亡中的作用。将大鼠晶状体上皮外植体用亚硒酸钠培养。亚硒酸盐导致上皮外植体将乳酸脱氢酶（LDH）释放到培养基中。在LDH释放过程中，通过逆转录聚合酶链反应（RT-PCR）观察到Egr-1的mRNA表达增加。为了进一步检测Egr-1在亚硒酸盐诱导的细胞死亡中的作用，用针对Egr-1的反义寡核苷酸处理小鼠晶状体上皮细胞系（α-TN4细胞）。针对Egr-1的反义寡核苷酸显著降低了Egr-1蛋白的表达和LDH的释放。这些结果表明，Egr-1活性增加可能是亚硒酸盐诱导晶状体上皮细胞死亡的一个因素。
