Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures

Pogue, Aileen I.; Percy, Maire E.; Cui, Jian; Li, Yuan Yuan; Bhattacharjee, Surjyadipta; Hill, James M.; Kruck, Theo P.A.; Zhao, Yuhai; Lukiw, Walter J.

doi:10.1016/j.jinorgbio.2011.05.012

Cited by 72 publications

(83 citation statements)

References 37 publications

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“…Studies involving of human neuronal-glial (HNG) cells in primary co-culture carried out over the past 20 years have proved highly informative in neurodegenerative disease mechanistic studies [21,[34][35][36]. These and the present study should encourage other researchers to experiment with the organic and inorganic neurotoxic factors utilized and characterized in this study, and further explore their effects in HNG cells and other more specific human neural cell systems.…”

Section: Discussionmentioning

confidence: 79%

“…These and the present study should encourage other researchers to experiment with the organic and inorganic neurotoxic factors utilized and characterized in this study, and further explore their effects in HNG cells and other more specific human neural cell systems. A major challenge in neurodegenerative disorders is the connection between intracellular protein inclusions, which are different for different neurodegenerative diseases, neuroinflammation, and the functional loss of neurons and synapses [35][36][37][38]. Laboratories that have access to fresh human brain tissue, might consider co-culturing dopaminergic, midbrain, or hippocampal cells (mostly affected in IPD and AD, respectively) in parallel with astrocytic or glial cells in order to explore the relation between exposure to ROS-inducing factors and formation of intracellular inclusions.…”

Section: Discussionmentioning

confidence: 99%

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Generation of Reactive Oxygen Species (Ros) and Pro-Inflammatory Signaling in Human Brain Cells in Primary Culture

Bjattacharjee¹

2013

J Alzheimers Dis Parkinsonism

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Oxidative Stress-Induced Neuron Toxicity Keywords: Alzheimer's disease; Apoptosis; Fenton chemistry; Human neural cells; Inflammation; Metal sulfates; Synergistic effects IntroductionAge-related neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) have long been associated with free radical-induced oxidative stress, and these are driven by the nonhomeostatic production of reactive oxygen species (ROS) [1][2][3][4][5][6][7][8]. ROS are highly reactive and charged metabolic intermediates that attack DNA, RNA, protein and lipids to leave oxidized cellular components that are genotoxic or cytotoxic, and unable to perform their normal biological functions. While cellular systems have evolved elaborate anti-oxidant systems to neutralize the effects of ROS, degenerative disease processes such as those associated with AD and PD may overwhelm these neuroprotective anti-oxidant defenses [5][6][7][8][9][10][11]. The progressive generation of ROS during the course of human aging lies at the core of the free radical theory of aging originally proposed by Harman 55 years ago [10]; this theory implies that aging is associated with increased ambient levels of ROS, ROS-oxidized biomolecules and their deleterious biological effects [8][9][10][11].Based on a previously verified and highly sensitive assay in vitro stress-test system for the effects of ROS on human brain cell pathogenic gene expression [9,[12][13][14][15][16][17][18], in these experiments we tested the ROSinducing effects of the two most widely used non-prescription drugs -simvastatin and acetylsalicylic acid (aspirin); the pro-inflammatory cytokines -interleukin-6 (IL-6) and interleukin-1beta (IL-1β); tissue necrosis factor alpha (TNFα); amyloid precursor protein (βAPP) and the AD-associated neurotoxic peptides -Aβ40 and Aβ42; the neurotoxic metals -Hg, Cu, Zn, Mn, Fe and Al; and hydrogen peroxide at 50 nM or 100 nM ambient concentrations in the growth medium of human neuronal-glial (HNG) cells in primary culture. Several of these factors were tested in combination. Because brain cells sense applied physiological stress as a form of impending cellular injury, they respond through an up-regulation of immune and inflammatory Materials and Methods Reagents and antibodiesSimvastatin (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl} -3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl2,2-dimethylbutanoate; S6196) and acetylsalicylic acid (O-acetylsalicylic acid, ASA, aspirin; A5376) were dissolved in DMSO and ultrapure water, respectively, following instructions provided by the manufacturer (Sigma-Aldrich Chemical, St. Louis, MO). When appropriate, control HNG cells received DMSO at concentrations used in simvastatin and ASA assays. Solutions of βAPP, Aβ40 and Aβ42 were prepared as previously described [21][22][23]. All trace metals were used as ultrapure sulfates [14]. Briefly, Biochemika MicroSelect© ultrapure reagents for molecular biology, including MgSO 4 (63133), Mn(II) sulfate AbstractThe cellular gene...

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Generation of Reactive Oxygen Species (Ros) and Pro-Inflammatory Signaling in Human Brain Cells in Primary Culture

Bjattacharjee¹

2013

J Alzheimers Dis Parkinsonism

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“…[102][103][104] CFH expression is significantly downregulated in the degenerating brain and retina, suggesting that insufficient quantities of this RCA regulator lead to excessive activation of the innate immune response and proinflammatory signaling. [105][106][107][108][109][110][111][112][113][114][115][116][117] There are many shared pathologic characteristics of Alzheimer's disease (AD) and AMD, including decreases and/or dysfunction in CFH. 118 CFH inhibits alternative pathway activation both in plasma and on cell surfaces by promoting C3b proteolysis.…”

Section: Mirnas As Regulators Of the Inflammatory Process An Importamentioning

confidence: 99%

The role of epigenetics in age-related macular degeneration

Gemenetzi

Lotery

2014

Eye

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It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcrip-

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“…These miRNA are involved in astroglial cell proliferation and inflammatory responses, respectively, and are significantly up-regulated in Alzheimer's disease (153) . Modulation of specific miRNA by Fe alone has yet to be demonstrated; however, an important role for ferric haem has been demonstrated in the modulation of the miRNA processing machinery.…”

Section: Iron Magnesium and Aluminiummentioning

confidence: 99%

The role of vitamins and minerals in modulating the expression of microRNA

et al. 2014

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A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

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Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures

Cited by 72 publications

References 37 publications

Generation of Reactive Oxygen Species (Ros) and Pro-Inflammatory Signaling in Human Brain Cells in Primary Culture

Generation of Reactive Oxygen Species (Ros) and Pro-Inflammatory Signaling in Human Brain Cells in Primary Culture

The role of epigenetics in age-related macular degeneration

The role of vitamins and minerals in modulating the expression of microRNA

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