DRAM1 Protects Neuroblastoma Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Injury via Autophagy

Yu, Meihong; Jiang, Yugang; Feng, Qian; Ouyang, Yan; Gan, Jie

doi:10.3390/ijms151019253

Cited by 25 publications

(13 citation statements)

References 42 publications

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“…Other identified variants point to genes involved in autophagy and apoptotic processes , such as DRAM1 and F0X03 , both related to brainstem volumes. DRAM1 encodes a lysosomal membrane protein involved in activating TP53-mediated autophagy and apoptosis, 60 and mouse models mimicking cerebral ischemia and reperfusion have found that inhibiting the expression of DRAM1 worsens cell injury 61 . The most significant variant located 9Kb downstream from DRAM1 was also associated with a CpG site proximate to active TSS upstream of that gene in several mature brain tissues (Table S5 and Figure S3.B).…”

Section: Discussionmentioning

confidence: 99%

Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

Satizábal

Adams

Hibar

et al. 2017

Preprint

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Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related to the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus, using genome-wide association analyses in over 40,000 individuals from CHARGE, ENIGMA and the UK-Biobank. We show that variability in subcortical volumes is heritable, and identify 25 significantly associated loci (20 novel). Annotation of these loci utilizing gene expression, methylation, and neuropathological data identified 62 candidate genes implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

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Section: Discussionmentioning

confidence: 99%

Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

Satizábal

Adams

Hibar

et al. 2017

Preprint

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“…40 This existing model could mimic extracellular conditions in cerebral ischemia and subsequently reperfusion, and is commonly used as a model for in vitro research. 41 In brief, to induce OGD/R injury, cultured primary human astrocytes were cultured in 12-well plate.…”

Section: Methodsmentioning

confidence: 99%

Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation

et al. 2016

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Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect. Moreover, HHcy increased unfolded protein response. Interestingly, Vitamin B supplementation restored autophagic flux, alleviated ER stress, and reversed lysosomal dysfunction due to HHCy. Furthermore, the autophagy inducer, rapamycin was able to relieve ER stress and reverse lysosomal dysfunction caused by HHcy in vitro. Inhibition of autophagy by HHcy exacerbated cellular injury during oxygen and glucose deprivation and reperfusion (OGD/R), and oxidative stress. These effects were prevented by Vitamin B co-treatment, suggesting that it may be helpful in relieving detrimental effects of HHcy in ischemia/reperfusion or oxidative stress. Collectively, these findings show that Vitamin B therapy can reverse defects in cellular autophagy and ER stress due to HHcy; and thus may be a potential treatment to reduce ischemic damage caused by stroke in patients with HHcy.

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“…DRAM1, DNA damage regulated autophagy modulator 1, was reported to increase autophagy flux through promoting lysosomal acidification and protease activation [ 37 ]. It was found that DRAM1 knockdown inhibited autophagy flux and aggravated cell injury in Neuro-2a cells [ 38 ]. A recent study has shown that CLs induced cell necrosis involved in late-stage autophagic flux inhibition [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Cationic liposomes induce cytotoxicity in HepG2 via regulation of lipid metabolism based on whole-transcriptome sequencing analysis

Liu

Cui

Chen

et al. 2018

BMC Pharmacol Toxicol

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BackgroudCationic liposomes (CLs) can be used as non-viral vectors in gene transfer and drug delivery. However, the underlying molecular mechanism of its cytotoxicity has not been well elucidated yet.MethodsWe herein report a systems biology approach based on whole-transcriptome sequencing coupled with computational method to identify the predominant genes and pathways involved in the cytotoxicity of CLs in HepG2 cell line.ResultsFirstly, we validated the concentration-dependent cytotoxicity of CLs with an IC50 of 120 μg/ml in HepG2 exposed for 24 h. Subsequently, we used whole-transcriptome sequencing to identify 220 (77 up- and 143 down-regulated) differentially expressed genes (DEGs). Gene ontology (GO) and pathway analysis showed that these DEGs were mainly related to cholesterol, steroid, lipid biosynthetic and metabolic processes. Additionally, “key regulatory” genes were identified using gene act, pathway act and co-expression network analysis, and expression levels of 11 interested altered genes were confirmed by quantitative real time PCR. Interestingly, no cell cycle arrest was observed through flow cytometry.ConclusionsThese data are expected to provide deep insights into the molecular mechanism of CLs cytotoxicity.

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DRAM1 Protects Neuroblastoma Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Injury via Autophagy

Cited by 25 publications

References 42 publications

Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation

Cationic liposomes induce cytotoxicity in HepG2 via regulation of lipid metabolism based on whole-transcriptome sequencing analysis

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