Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs

Christofidou‐Solomidou, Melpo; Pietrofesa, Ralph A.; Arguiri, Evguenia; McAlexander, Melissa A.; Witwer, Kenneth W.

doi:10.4161/cbt.28905

Cited by 24 publications

(27 citation statements)

References 59 publications

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“…Furthermore, since Tat is known to induce astrogliosis our findings also suggest that exposure of astrocytes to Tat could induce expression of miRs-34a & -138, leading in turn, to downregulation of SIRT1 with a concomitant upregulation of GFAP. These data are consistent with previous studies which indicate that both miRs-34a & -138 play important roles in CNS diseases and the immune system [41, 79, 86–90]. …”

Section: Discussionsupporting

confidence: 93%

Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND

Liao

Lü

et al. 2017

J Neuroimmune Pharmacol

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Astrocyte activation is a hallmark of HIV infection and aging in the CNS. In chronically infected HIV patients, prolonged activation of astrocytes has been linked to accelerated aging including but not limited to neurocognitive impairment and frailty. The current study addresses the role of HIV protein Tat in inducing a set of small noncoding microRNAs (miRNA) that play critical role in astrogliosis. In our efforts to link astrocyte activation as an indicator of aging, we assessed the brains of both wild type and HIV transgenic rats for the expression of glial fibrillary acidic protein (GFAP). As expected, in the WT animals we observed age-dependent increase in astrogliosis in the older animals compared to the younger group. Interestingly, compared to the young WT group, young HIV Tg rats exhibited higher levels of GFAP in this trend was also observed in the older HIV Tg rats compared to the older WT group. Based on the role of SIRT1 in aging and the regulation of SIRT1 by miRNAs-34a and -138, we next assessed the expression levels of these miRs in the brains of both the young an old WT and HIV Tg rats. While there were no significant differences in the young WT versus the HIV Tg rats, in the older HIV Tg rats there was a significant upregulation in the expression of miRs-34a & -138 in the brains. Furthermore, increased expression of miRs-34a & -138 in the older Tg rats, correlated with a concomitant decrease in their common anti-aging target protein SIRT1, in the brains of these animals. To delineate the mechanism of action we assessed the role of HIV-Tat (present in the Tg rats) in inducing miRs-34a & -138 in both the primary astrocytes and the astrocytoma cell line A172, thereby leading to posttranscriptional suppression of SIRT1 with a concomitant up regulation of NF-kB driven expression of GFAP.

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Section: Discussionsupporting

confidence: 93%

Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND

Liao

Lü

et al. 2017

J Neuroimmune Pharmacol

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“…As a pilot study, a smaller animal numbers is typically used to generate data as the foundation for future experiments. For example, exciting insights have been generated from some pilot studies with limited number of animals for further studies [47, 48]. With our previous experience in the lesion size expected in normal chow or high fat diet in the ApoE −/− mice, the current number of mice used were justified in generating meaningful statics [49].…”

Section: Discussionmentioning

confidence: 99%

High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE−/− mice

et al. 2016

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BackgroundAtherosclerosis appears to have multifactorial causes – microbial component like lipopolysaccharides (LPS) and other pathogen associated molecular patterns may be plausible factors. The gut microbiota is an ample source of such stimulants, and its dependent metabolites and altered gut metagenome has been an established link to atherosclerosis. In this exploratory pilot study, we aimed to elucidate whether microbial intervention with probiotics L. rhamnosus GG (LGG) or pharmaceuticals telmisartan (TLM) could improve atherosclerosis in a gut microbiota associated manner.MethodsAtherosclerotic phenotype was established by 12 weeks feeding of high fat (HF) diet as opposed to normal chow diet (ND) in apolipoprotein E knockout (ApoE−/−) mice. LGG or TLM supplementation to HF diet was studied.ResultsBoth LGG and TLM significantly reduced atherosclerotic plaque size and improved various biomarkers including endotoxin to different extents. Colonial microbiota analysis revealed that TLM restored HF diet induced increase in Firmicutes/Bacteroidetes ratio and decrease in alpha diversity; and led to a more distinct microbial clustering closer to ND in PCoA plot. Eubacteria, Anaeroplasma, Roseburia, Oscillospira and Dehalobacteria appeared to be protective against atherosclerosis and showed significant negative correlation with atherosclerotic plaque size and plasma adipocyte – fatty acid binding protein (A-FABP) and cholesterol.ConclusionLGG and TLM improved atherosclerosis with TLM having a more distinct alteration in the colonic gut microbiota. Altered bacteria genera and reduced alpha diversity had significant correlations to atherosclerotic plaque size, plasma A-FABP and cholesterol. Future studies on such bacterial functional influence in lipid metabolism will be warranted.

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“…We demonstrated a significant impairment of blood oxygenation and systemic oxidative stress, related to repeated radiation and hyperoxia exposure as well as increased pulmonary inflammation and bronchoalveolar lavage protein levels indicating the development of significant lung tissue injury. In the current study, we used the same model to evaluate dietary administration of wholegrain flaxseed, a grain with potent antioxidant, anti-inflammatory and anti-fibrotic properties, shown by our group to be protective in lung tissues [12-14,34,43]. We report here for the first time that in a novel model of repeat hyperoxia and radiation exposure, flaxseed intake mitigated adverse effects in lung, thus proving to be a promising countermeasure to potential health risks associated with space exploration.…”

Section: Discussionmentioning

confidence: 99%

“…Our group was the first to show that dietary FS supplementation could also reduce lung inflammation and lipid peroxidation in murine models of acid aspiration and hyperoxia [12] and more recently, in lung ischemia/reperfusion injury related to transplantation damage [13]. Our group pioneered the studies establishing the radioprotective and radiation mitigating properties in lung of FS and FS lignan component [14,33-35,43]. Evaluating the usefulness of this nutritional agent in blunting adverse effects in lung by the cycling and combinatorial effects of hyperoxia and radiation exposures is novel as this agent has never been tested as countermeasure relevant to space travel complications.…”

Section: Discussionmentioning

confidence: 99%

Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

Pietrofesa

Solomides

Christofidou‐Solomidou

2014

J Pulm Respir Med

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Background Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures. Methods We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals. Results At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung. Conclusion Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early tissue oxidative damage associated with space exploration.

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Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs

Cited by 24 publications

References 59 publications

Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND

Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND

Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

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