Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.
Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Mingming
M
Zhu
Department of Pediatrics, Ganzhou Maternal and Child Health Hospital, Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
Bingfei
B
Li
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Xiao
X
Ma
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Cong
C
Huang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Rui
R
Wu
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Weiwei
W
Zhu
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Xiaoting
X
Li
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Zhaofeng
Z
Liang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Feifei
F
Deng
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Jianyun
J
Zhu
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Wei
W
Xie
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Xue
X
Yang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Ye
Y
Jiang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Shijia
S
Wang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Jieshu
J
Wu
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Shanshan
S
Geng
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Chunfeng
C
Xie
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. cyzhong@njmu.edu.cn.
Caiyun
C
Zhong
Department of Pathology, Huaian First People's Hospital, Nanjing Medical University, Huaian, 223300, China. 642634656@qq.com.
Haiyan
H
Liu
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000633:toxicity*; D011753:Pyrones / Q000633:toxicity*
C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D011753:Pyrones; C067527:aluminum maltolate; D005492:Folic Acid
Aluminum; Apoptosis; Folic acid; Modulation; Neurodegenerative diseases; miR-19