Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation

Zhu, Mingming; Li, Bingfei; Ma, Xiao; Huang, Cong; Wu, Rui; Zhu, Wenzhen; Li, Xiaoting; Liang, Zhaofeng; Deng, Feifei; Zhu, Jianyun; Xie, Wei; Yang, Xue; Jiang, Ye; Wang, Shijia; Wu, Jieshu; Geng, Shanshan; Xie, Chunfeng; Zhong, Caiyun; Liu, Haiyan

doi:10.1007/s11064-016-1926-9

Cited by 20 publications

(15 citation statements)

References 46 publications

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“…When we compared the most significant up- or downregulated genes, we observed that most of the genes related to apoptosis ( TP53BP2, CSRNP1, TEAD, CDCA7, PPP1R15A ) were upregulated in Vac- or Adj-injected sheep. This is in agreement with other studies, in which aluminum-induced apoptosis in the human neuroblastoma cell line ( 58 ) and the expression of pro-apoptotic genes in human brain cells ( 55 ) were also found. In addition, some genes related to the immune response ( SKAP2, IGSF6, LST1, FGR, MAPK13 ), inflammatory response ( S100A12, ADGRE3, TREM1, STEAP4, NR4A3 ), cell growth ( HGF, CSF3R ), and cell-cell signaling ( AREG ) were upregulated in Vac-injected sheep but were downregulated in Adj-injected animals.…”

Section: Discussionsupporting

confidence: 93%

Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing

et al. 2018

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There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the aim of identifying the activated molecular signature. Blood samples were taken from each animal at the beginning and at the end of the experiment and PBMCs isolated. Total RNA and miRNA libraries were prepared and sequenced. After alignment to the Oar3.1 reference genome and differential expression with 3 programs, gene enrichment modeling was performed. For miRNAs, miRBase and RNAcentral databases were used for detection and characterization. Three expression comparisons were made: vaccinated animals at the beginning and at the end of the treatment, adjuvanted animals at the same times, and animals of both treatments at the end of the experiment. After exposure to both treatments, a total of 2,473; 2,980 and 429 differentially expressed genes were identified in vaccinated animals, adjuvanted animals and animals at the end of both treatments, respectively. In both adjuvant and vaccine treated animals the NF-κB signaling pathway was enriched. On the other hand, it can be observed a downregulation of cytokines and cytokine receptors in the adjuvanted group compared to the vaccinated group at the final time, suggesting a milder induction of the immune response when the adjuvant is alone. As for the miRNA analysis, 95 miRNAs were detected: 64 previously annotated in Ovis aries, 11 annotated in Bos taurus and 20 newly described. Interestingly, 6 miRNAs were differentially expressed in adjuvant treated animals, and 3 and 1 in the other two comparisons. Lastly, an integrated miRNA-mRNA expression profile was developed, in which a miRNA-mediated regulation of genes related to DNA damage stimulus was observed. In brief, it seems that aluminum-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that can stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated.

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Section: Discussionsupporting

confidence: 93%

Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing

et al. 2018

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“…Bcl-2 to play the antiapoptosis role, but also block the release of cyt-c to initiate the antiapoptosis mechanism, thereby protecting neurons against ischemic injury (Choi, Lee, Hong, & Lee, 2004;Liu et al, 2010). Moreover, Zhu et al (2016) found that miR-19b…”

Section: Discussionmentioning

confidence: 99%

Retracted: Protection of miR‐19b in hypoxia/reoxygenation‐induced injury by targeting PTEN

Liu

Han

Xiang

2019

Journal Cellular Physiology

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Objective To study the role and mechanism of microRNA 19b (miR‐19b) in hypoxia/reoxygenation (H/R)‐induced injury by targeting PTEN. Methods PC12 and BV2 cells induced by H/R were treated with miR‐19b mimics/inhibitors or small interfering PTEN (si‐PTEN), respectively. Lactate dehydrogenase (LDH) level, malondialdehyde (MDA), and superoxide dismutase (SOD) content was detected. Besides, cell viability and apoptosis were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, Hoechst33342 staining, and flow cytometry, whereas mitochondrial membrane potential (MMP) tested by JC‐1 assay, and reactive oxygen species (ROS) evaluated by the dichloro‐dihydro‐fluorescein diacetate assay. The ischemia/reperfusion (I/R) rats model was used to investigate the effects of miR‐19b in vivo test. The infarct area and apoptosis rates in brain tissues were detected by 2,3,5‐triphenyltetrazolium chloride and terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling staining, respectively. miR‐19b and PTEN/PI3K/Akt pathway‐related proteins were detected by quantitative reverse‐transcription polymerase chain reaction and western blot analysis. Results miR‐19b mimics could reduce LDH, MDA, and ROS levels and decline cell apoptosis, but enhance the viability, MMP, and SOD activity with decreased PTEN and cleaved caspase, as well as increased p‐Akt/Akt and Bcl‐2/Bax ratios in H/R‐induced PC12 and BV2 cells. However, miR‐19b inhibitors led to completely opposite results to aggravate H/R‐induced cell injury. Meanwhile, si‐PTEN could reverse the effect of miR‐19b inhibitors on H/R‐induced injury. Moreover, treatment with miR‐19b agomir after I/R in vivo sufficiently decreased infarct area and reduced apoptosis rates by targeting PTEN through the regulation of the PI3K/Akt pathway. Conclusion miR‐19b could inhibit oxidative stress, enhance cell MMP, promote cell survival, and inhibit cell apoptosis by targeting PTEN via the regulation of the PI3K/Akt pathway, thus playing the neuronal protective effects.

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“…Effects of Vitamin E (alpha-tocopherol and the water-soluble analog Trolox) were assessed in comparison to other antioxidant agents of alimentary origin, in order to test their action specificity. In particular, for our experiments we specifically selected: beta-carotene (21, 22), lycopene (22, 23), lutein (24), folic acid (25), ascorbic acid/Vitamin C (26), retinol/Vitamin A (27), Vitamin K1/phylloquinone, and Vitamin K2/menaquinones (28, 29).…”

Section: Methodsmentioning

confidence: 99%

“…For acute treatment, a single slice was incubated, from 40 min before HFS induction and for the duration of the whole experiment (about 1 h), in a bath solution containing the drug dissolved in Krebs' solution. Selected compounds were used in bath at the respective dose of: alpha-tocopherol = 100 μM and Trolox = 100 μM (9); beta-carotene = 100 μM (30); lutein = 20 μM (24); lycopene = 5 μM (22, 23); folic acid = 100 μM (25); Vitamin A = 1 μM (27); Vitamin C = 1–3 mM (26); Vitamin K1 = 20 μM, and Vitamin K2 = 10 μM (28, 29).…”

Section: Methodsmentioning

confidence: 99%

Dietary Vitamin E as a Protective Factor for Parkinson's Disease: Clinical and Experimental Evidence

et al. 2019

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Effective disease-modifying treatments are an urgent need for Parkinson's disease (PD). A putative successful strategy is to counteract oxidative stress, not only with synthetic compounds, but also with natural agents or dietary choices. Vitamin E, in particular, is a powerful antioxidant, commonly found in vegetables and other components of the diet. In this work, we performed a questionnaire based case-control study on 100 PD patients and 100 healthy controls. The analysis showed that a higher dietary intake of Vitamin E was inversely associated with PD occurrence independently from age and gender (OR = 1.022; 95% CI = 0.999–1.045; p < 0.05), though unrelated to clinical severity. Then, in order to provide a mechanistic explanation for such observation, we tested the effects of Vitamin E and other alimentary antioxidants in vitro , by utilizing the homozygous PTEN-induced kinase 1 knockout ( PINK1 −/− ) mouse model of PD. PINK1 −/− mice exhibit peculiar alterations of synaptic plasticity at corticostriatal synapses, consisting in the loss of both long-term potentiation (LTP) and long-term depression (LTD), in the absence of overt neurodegeneration. Chronic administration of Vitamin E (alpha-tocopherol and the water-soluble analog trolox) fully restored corticostriatal synaptic plasticity in PINK1 −/− mice, suggestive of a specific protective action. Vitamin E might indeed compensate PINK1 haploinsufficiency and mitochondrial impairment, reverting some central steps of the pathogenic process. Altogether, both clinical and experimental findings suggest that Vitamin E could be a potential, useful agent for PD patients. These data, although preliminary, may encourage future confirmatory trials.

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Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation

Cited by 20 publications

References 46 publications

Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing

Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing

Retracted: Protection of miR‐19b in hypoxia/reoxygenation‐induced injury by targeting PTEN

Dietary Vitamin E as a Protective Factor for Parkinson's Disease: Clinical and Experimental Evidence

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