Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis

Gao, Dan; Pararasa, Chathyan; Dunston, Christopher R.; Bailey, Clifford J.; Griffiths, Helen R.

doi:10.1016/j.freeradbiomed.2012.05.026

Cited by 60 publications

(48 citation statements)

References 43 publications

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“…Nevertheless, the data reported here confirm the suggestion that α-tocopherol is acting hermetically e.g. through promoting autophagic clearance of intracellular fibrotic proteins [11] or is a correlate for nutrients which may improve cardiovascular health, such as MUFA which are antiinflammatory in vitro and in vivo [17,24]. Epidemiological evidence suggests that consumption of a diet enriched in MUFA and tocopherols including nuts, reduces BP and lipid levels [6,[25][26][27].…”

Section: Discussionsupporting

confidence: 76%

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Choudhury

Clark

Griffiths

2014

Free Radical Research

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Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men.Healthy middle-aged men (56+5.8years), healthy young men (22.1+2.9years) and young men with two or more CV risk factors (27.3+5years) consumed 50g almond /day for 4 weeks. A control group maintained habitual diets over the same period.Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50g almond/day for four weeks (p<0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas total, HDL and LDL cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by almond intake. In the almond consuming groups, flow mediated dilatation (FMD) was improved and diastolic blood pressure was reduced significantly after 4 weeks, but systolic blood pressure was only reduced in healthy men.In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy mean men aged between 20 and 70 without effect on plasma lipids or markers of oxidative stress.3

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Section: Discussionsupporting

confidence: 76%

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Choudhury

Clark

Griffiths

2014

Free Radical Research

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“…We have previously shown in monocytes that saturated fatty acids can induce mitochondrial ROS, GSH depletion and can direct metabolism towards glycolysis [19,32]. Here, we have shown that the fatty acids, palmitate or oleate, inhibit mitochondrial metabolism in MCF7 cells and this inhibitory effect was enhanced by BAR; palmitate also elicited a significant increase in Mitosox oxidation and the effect of co-incubation with BAR was additive.…”

Section: Discussionmentioning

confidence: 59%

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Refaat

Pararasa

Arif

et al. 2017

Free Radical Research

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Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR. Incubation with BAR caused a time-dependent migratory inhibition and an associated decrease in mitochondrial respiration. Both migratory and mitochondrial inhibition by BAR were further enhanced in the presence of fatty acids. In addition to the activation of Nrf2, BAR altered the expression of target mRNA GCLC and UCP1. After 24 h, BAR inhibited both glycolytic capacity, reserve (p < 0.05) and oxidative phosphorylation (p < 0.001) with an associated increase in mitochondrial ROS and loss of intracellular glutathione in MCF7 cells; however, impairment of mitochondrial activity was prevented by N-acetyl cysteine. The fatty acid, palmitate, increased mitochondrial ROS, impaired migration and oxidative phosphorylation but palmitate toxicity towards MCF7 could not be inhibited by N-acetyl cysteine suggesting that they exert effects through different pathways. BAR-activated AKT, induced DNA damage and inhibited cell proliferation. When the proteasome was inhibited, there was loss of BAR-mediated changes in p65 phosphorylation and SOD2 expression suggesting non-canonical NFkB signaling effects. These data suggest that BAR-induced ROS are important in inhibiting MCF7 migration and metabolism by negatively affecting glycolytic capacity and mitochondrial function. ARTICLE HISTORY

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“…To understand how PA and LPS have a synergy on IL-6 expression, we focused on CER since it is known that uptake of PA increases cellular level of palmitoyl-CoA and subsequent CER production (13,28), and increased CER level enhances LPS signaling (47). The findings from the present study have provided the following evidence that CER plays a crucial role in the augmentation of LPS-stimulated IL-6 expression by PA. First, our results showed that PA and LPS exerted a similar synergy on both IL-6 expression and CER production and a similar kinetics on both IL-6 expression and CER production (Figs.…”

Section: Discussionmentioning

confidence: 68%