Ma Xinlong, Shang Feng, Zhang Qiuxia, Lin Qingtang, Han Shuo, Shan Yongzhi, Du Jianxin, Ling Feng, Zhang Hongqi, Xu Geng
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, P.R. China.
Mol Med Rep. 2017 Aug;16(2):2199-2204. doi: 10.3892/mmr.2017.6809. Epub 2017 Jun 20.
Aluminum-maltolate (Al‑Malt) is a potent apoptosis inductor, which has been widely reported as an etiologic factor in Alzheimer's disease (AD). MicroRNA-322 (miR‑322) is a vital regulator in various biological processes. The aim of the current study was to identify the role and possible underlying mechanism of miR‑322 in Al‑Malt‑induced apoptosis. Eight concentrations of Al‑Malt were prepared and used for treating the human neuroblastoma cell line, SH‑SY5Y. Subsequent to treatment with Al‑Malt for 3 days, cell viability, apoptosis and the expression levels of apoptosis‑associated factors were measured. In addition, the mRNA expression level of miR‑322 was monitored. Furthermore, cells were transfected with an miR‑322 mimic and/or treated with Al‑Malt, and cell viability, apoptosis and the expression levels of apoptosis‑associated factors were measured again. Al‑Malt significantly inhibited cell viability, but promoted apoptosis. The apoptosis‑associated factors, V‑Myc avian myelocytomatosis viral oncogene homolog (c‑Myc), Bcl-2-associated X protein, caspase‑3 and cleaved caspase‑3 were markedly upregulated by Al‑Malt. The mRNA expression level of miR‑322 was negatively regulated by Al‑Malt. Furthermore, miR‑322 attenuated the apoptosis induced by Al‑Malt and recovered the expression changes of these four factors. Thus, miR‑322 may attenuate Al‑Malt‑induced apoptosis by recovering the expression change of c‑Myc. Furthermore, miR‑322 may be involved in the pathogenesis of Al‑Malt‑associated AD.
麦芽酚铝（Al-Malt）是一种有效的凋亡诱导剂，已被广泛报道为阿尔茨海默病（AD）的一个病因。微小RNA-322（miR-322）是各种生物过程中的重要调节因子。本研究的目的是确定miR-322在Al-Malt诱导的细胞凋亡中的作用及可能的潜在机制。制备了八种浓度的Al-Malt，并用于处理人神经母细胞瘤细胞系SH-SY5Y。用Al-Malt处理3天后，检测细胞活力、凋亡及凋亡相关因子的表达水平。此外，监测miR-322的mRNA表达水平。进一步地，用miR-322模拟物转染细胞和/或用Al-Malt处理，再次检测细胞活力、凋亡及凋亡相关因子的表达水平。Al-Malt显著抑制细胞活力，但促进细胞凋亡。Al-Malt使凋亡相关因子V-Myc禽成髓细胞瘤病毒癌基因同源物（c-Myc）、Bcl-2相关X蛋白、半胱天冬酶-3和裂解的半胱天冬酶-3明显上调。Al-Malt对miR-322的mRNA表达水平起负调控作用。此外，miR-322减弱了Al-Malt诱导的细胞凋亡，并恢复了这四种因子的表达变化。因此，miR-322可能通过恢复c-Myc的表达变化来减弱Al-Malt诱导的细胞凋亡。此外，miR-322可能参与了Al-Malt相关AD的发病机制。
