Amadio Marialaura, Scapagnini Giovanni, Davinelli Sergio, Calabrese Vittorio, Govoni Stefano, Pascale Alessia
Department of Drug Sciences, Section of Pharmacology, University of Pavia Pavia, Italy.
Department of Medicine and Health Sciences, University of Molise Campobasso, Italy ; Inter-University Consortium "SannioTech" Benevento, Italy.
Front Cell Neurosci. 2015 Jan 15;8:459. doi: 10.3389/fncel.2014.00459. eCollection 2014.
Heme oxygenase-1 (HO-1) is an inducible rate-controlling enzyme of heme catabolism. The cytoprotective function of HO-1 activity has been verified in multiple studies, and together with its by-products is considered a key component of the cellular stress response. The transcriptional induction of HO-1 has been largely studied in response to multiple forms of stressful stimuli but our understanding of HO-1 post-transcriptional control mechanisms in neuronal cells is currently lacking. In the present report we show the involvement of the RNA-binding proteins (RBPs) embryonic lethal abnormal vision (ELAV) in the regulation of HO-1 gene expression. Our study demonstrates a specific binding between HO-1 messenger RNA (mRNA) and ELAV proteins, accompanied by an increased expression of HO-1 at protein level, in a human neuroblastoma cell line treated with hemin. Clarifying the induction of HO-1 expression at post-transcriptional level may open therapeutic perspectives for treatments associated with the modulation of HO-1 expression.
血红素加氧酶-1(HO-1)是血红素分解代谢的一种诱导性限速酶。HO-1活性的细胞保护功能已在多项研究中得到证实,并且连同其副产物被认为是细胞应激反应的关键组成部分。HO-1的转录诱导在应对多种形式的应激刺激方面已得到大量研究,但目前我们对神经元细胞中HO-1转录后调控机制的了解尚缺。在本报告中,我们展示了RNA结合蛋白(RBP)胚胎致死异常视觉(ELAV)参与HO-1基因表达的调控。我们的研究表明,在用血红素处理的人神经母细胞瘤细胞系中,HO-1信使核糖核酸(mRNA)与ELAV蛋白之间存在特异性结合,同时HO-1在蛋白水平的表达增加。阐明HO-1在转录后水平的表达诱导可能为与HO-1表达调节相关的治疗开辟治疗前景。