5-氨基乙酰丙酸对神经母细胞瘤 SH-SY5Y 细胞低无机磷的神经保护作用。

Neuroprotective effect of 5-aminolevulinic acid against low inorganic phosphate in neuroblastoma SH-SY5Y cells.

机构信息

Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan.

Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

出版信息

Sci Rep. 2017 Jul 18;7(1):5768. doi: 10.1038/s41598-017-06406-6.

PiT-1 (encoded by SLC20A1) and PiT-2 (encoded by SLC20A2) are type-III sodium-dependent phosphate cotransporters (NaPiTs). Recently, SLC20A2 mutations have been found in patients with idiopathic basal ganglia calcification (IBGC), and were predicted to bring about an inability to transport Pi from the extracellular environment. Here we investigated the effect of low Pi loading on the human neuroblastoma SH-SY5Y and the human glioblastoma A172 cell lines. The results show a different sensitivity to low Pi loading and differential regulation of type-III NaPiTs in these cells. We also examined whether 5-aminolevulinic acid (5-ALA) inhibited low Pi loading-induced neurotoxicity in SH-SY5Y cells. Concomitant application of 5-ALA with low Pi loading markedly attenuated low Pi-induced cell death and mitochondrial dysfunction via the induction of HO-1 by p38 MAPK. The findings provide us with novel viewpoints to understand the pathophysiology of IBGC, and give a new insight into the clinical prevention and treatment of IBGC.

PiT-1（由 SLC20A1 编码）和 PiT-2（由 SLC20A2 编码）是 III 型钠依赖性磷酸盐共转运体（NaPiTs）。最近，在特发性基底节钙化（IBGC）患者中发现了 SLC20A2 突变，据预测，这些突变会导致无法从细胞外环境中转运 Pi。在这里，我们研究了低 Pi 负荷对人神经母细胞瘤 SH-SY5Y 和人神经胶质瘤 A172 细胞系的影响。结果表明，这些细胞对低 Pi 负荷的敏感性不同，III 型 NaPiTs 的调节也不同。我们还研究了 5-氨基乙酰丙酸（5-ALA）是否抑制了 SH-SY5Y 细胞中低 Pi 负荷诱导的神经毒性。低 Pi 负荷与 5-ALA 同时应用通过 p38 MAPK 诱导 HO-1，显著减轻低 Pi 诱导的细胞死亡和线粒体功能障碍。这些发现为我们理解 IBGC 的病理生理学提供了新的观点，并为 IBGC 的临床预防和治疗提供了新的思路。