Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand.
Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
Sci Rep. 2017 Aug 23;7(1):9194. doi: 10.1038/s41598-017-09321-y.
Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor frequently used in combination with other antiretroviral agents for highly active antiretroviral therapy (HAART) of patients infected with the human immunodeficiency virus type 1 (HIV-1). However NVP can cause serious, life-threatening complications. Hepatotoxicity is one of the most severe adverse effects, particularly in HIV patients with chronic hepatitis C virus co-infection as these patients can develop liver toxicity after a relatively short course of treatment. However, the mechanism of NVP-associated hepatotoxicity remains unclear. This study sought to investigate the effect of NVP on protein expression in liver cells using a proteomic approach. HepG2 cells were treated or not treated with NVP and proteins were subsequently resolved by two-dimensional gel electrophoresis. A total of 33 differentially regulated proteins were identified, of which nearly 40% (13/33) were mitochondrial proteins. While no obvious differences were observed between NVP treated and untreated cells after staining mitochondria with mitotracker, RT-PCR expression analysis of three mitochondrially encoded genes showed all were significantly up-regulated in NVP treated cells. Mitochondrial dysfunction was observed in response to treatment even with slightly sub-optimal therapeutic treatment concentrations of NVP. This study shows that NVP induces mitochondrial dysregulation in HepG2 cells.
奈韦拉平（NVP）是一种非核苷类逆转录酶抑制剂，常与其他抗逆转录病毒药物联合用于感染人类免疫缺陷病毒 1 型（HIV-1）的患者的高效抗逆转录病毒治疗（HAART）。然而，NVP 会导致严重的、危及生命的并发症。肝毒性是最严重的不良反应之一，特别是在 HIV 合并慢性丙型肝炎病毒感染的患者中，这些患者在相对较短的疗程后可能会发生肝毒性。然而，NVP 相关肝毒性的确切机制仍不清楚。本研究旨在采用蛋白质组学方法研究 NVP 对肝细胞蛋白表达的影响。用 NVP 处理或不处理 HepG2 细胞，随后通过二维凝胶电泳分离蛋白质。共鉴定出 33 个差异调节蛋白，其中近 40%（13/33）为线粒体蛋白。在用 mitotracker 染色线粒体后，NVP 处理和未处理的细胞之间没有明显差异，但 RT-PCR 表达分析显示，NVP 处理的细胞中所有三个线粒体编码基因均显著上调。即使 NVP 的治疗浓度略低于最佳治疗浓度，也会观察到线粒体功能障碍。本研究表明，NVP 诱导 HepG2 细胞中线粒体失调。
