Lungu G, Kuang X, Stoica G, Wong P K Y
Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, USA.
Acta Virol. 2010;54(1):27-32. doi: 10.4149/av_2010_01_27.
The retrovirus ts1 is a mutant of Moloney murine leukemia virus (MoMuLV) that causes neurodegeneration (ND) in susceptible mice. Our previous studies showed that the antioxidant drug monosodium luminol (GVT) prevented the development of ND in ts1-infected mice. In this study, we analyzed effect of GVT on the expression of B-cell lymphoma-2 protein (Bcl-2) and vascular endothelial growth factor (VEGF) in central nervous system (CNS) tissues of these animals. Our data showed that GVT treatment of ts1-infected mice significantly increased their expression of Bcl-2 and VEGF in brainstem compared with ts1-infected untreated mice. We also studied the expression of specific microRNAs (miRNAs) such as miRNA-15 and -16 (targeting Bcl-2), and miRNA-20 (targeting VEGF). We found that the expression of miRNAs inversely correlated with the upregulation of their target proteins in ts1-infected untreated as well as in GVT-treated-ts1-infected mice. The data showed that GVT treatment prevented ts1-induced ND at least in part by upregulating Bcl-2 and VEGF expression, what likely occurred as a consequence of downregulation of their corresponding miRNAs.
逆转录病毒ts1是莫洛尼鼠白血病病毒（MoMuLV）的一种突变体，可在易感小鼠中引发神经退行性变（ND）。我们之前的研究表明，抗氧化药物鲁米诺单钠（GVT）可预防ts1感染小鼠发生ND。在本研究中，我们分析了GVT对这些动物中枢神经系统（CNS）组织中B细胞淋巴瘤-2蛋白（Bcl-2）和血管内皮生长因子（VEGF）表达的影响。我们的数据显示，与未接受治疗的ts1感染小鼠相比，用GVT治疗ts1感染小鼠可显著增加其脑干中Bcl-2和VEGF的表达。我们还研究了特定微小RNA（miRNA）的表达，如靶向Bcl-2的miRNA-15和-16，以及靶向VEGF的miRNA-20。我们发现，在未接受治疗的ts1感染小鼠以及接受GVT治疗的ts1感染小鼠中，miRNA的表达与其靶蛋白的上调呈负相关。数据表明，GVT治疗至少部分通过上调Bcl-2和VEGF的表达来预防ts1诱导的ND，这可能是其相应miRNA下调的结果。
