The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice

Shaheen, Hazem M.; Onoda, Atsuto; Shinkai, Yusuke; Nakamura, Masayuki; El-Ghoneimy, Ashraf A.; El‐Sayed, Yasser S.; Takeda, Ken; Umezawa, Masakazu

doi:10.1016/j.ecoenv.2016.06.025

Cited by 13 publications

(7 citation statements)

References 62 publications

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“…By using targeted lipidomic analyses, we identified the specific sphingolipids that might be the targets of short- and medium-term PM 2.5 exposure, which partially supported our previous findings that short-term (14 days) black carbon exposure was associated with sphingolipid metabolism. 45 Our findings corroborate previous evidence linking air pollution to sphingolipid metabolism, 24–27,42–45 and suggest that sphingolipid synthesis may be enhanced after air pollution exposure. Notably, the levels of multiple species of hexosylceramides and sphingomyelins increased following PM 2.5 exposure, indicating that ceramides-to-sphingomyelins and ceramides-to-hexosylceramides transformations may be particularly relevant in the context of air pollution exposure.…”

Section: Discussionsupporting

confidence: 90%

“…We observed continuous increases in the levels of multiple sphingolipids (sphinganine, ceramide C24:0, hexosylceramides C16:0/C18:0/C20:0/C22:0/C24:0/C24:1, sphingomyelins C16:0/C18:0/C18:1/C20:0/ C22:0/ C24:0) associated with PM 2.5 exposure during 30 days before clinic visits. Previous in vitro and in vivo studies demonstrated that PM 2.5 , diesel exhaust, and cigarette smoke exposed for several days to months induced increased levels of ceramides, sphingomyelins, hexosylceramides, and lactosylceramides in human lung carcinoma cells and many tissues and organs of mice (ie, blood, the aorta, and the lungs), [24][25][26][27]42 which supported the current finding. Two epidemiological studies applying untargeted lipidomics suggested that sphingolipid metabolic pathways might be involved in the health responses to short-and mediumterm air pollution exposure, 43,44 yet there were uncertainties in sphingolipid characterization and quantification due to the limitations of the untargeted method itself.…”

Section: Discussionsupporting

confidence: 89%

“…An in vitro study demonstrated that human lung carcinoma cells with PM 2.5 exposed for 1 day showed marked increases in the levels of ceramides and sphingomyelins, 24 and similar effects were observed by an in vivo study which found that 7-day diesel exhaust exposure induced the production of ceramides in the mouse lung. 25 Additionally, another 2 in vivo studies found that intratracheal instillation of PM 2.5 and cigarette smoke (similar to particulate air pollution) exposure for 2 to 3 months increased ceramides, sphingomyelins, hexosylceramides, and lactosylceramides levels in the mouse blood and aorta, the circulating VLDL level, and the plaque areas, 26,27 suggesting that sphingolipids may mediate the proatherogenic effects of air pollution. However, no direct causal relationship has yet been demonstrated, and human data are lacking.…”

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confidence: 99%

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Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids

Wang

Gong

et al. 2022

ATVB

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Background: The pathophysiological mechanisms of air pollution-induced atherosclerosis are incompletely understood. Sphingolipids serve as biological intermediates during atherosclerosis development by facilitating production of proatherogenic apoB (apolipoprotein B)-containing lipoproteins. We explored whether sphingolipids mediate the proatherogenic effects of air pollution. Methods: This was a prospective panel study of 110 participants (mean age 56.5 years) followed from 2013 to 2015 in Beijing, China. Targeted lipidomic analyses were used to quantify 24 sphingolipids in 579 plasma samples. The mass concentrations of ambient particulate matter ≤2.5 μm in diameter (PM 2.5 ) were continuously monitored by a fixed station. We evaluated the associations between sphingolipid levels and average PM 2.5 concentrations 1–30 days before clinic visits using linear mixed-effects models and explored whether sphingolipids mediate PM 2.5 -associated changes in the levels of proatherogenic apoB-containing lipoproteins (LDL-C [low-density lipoprotein cholesterol] and non-HDL-C [nonhigh-density lipoprotein cholesterol]) using mediation analyses. Results: We observed significant increases in the levels of non-HDL-C and fourteen sphingolipids associated with PM 2.5 exposure, from short- (14 days) to medium-term (30 days) exposure time windows. The associations exhibited near-monotonic increases and peaked in 30-day time window. Increased levels of the sphingolipids, namely, sphinganine, ceramide C24:0, sphingomyelin C16:0/C18:0/C18:1/C20:0/C22:0/C24:0, and hexosylceramide C16:0/C18:0/C20:0/C22:0/C24:0/C24:1 significantly mediated 32%, 58%, 35% to 93%, and 23% to 86%, respectively, of the positive association between 14-day PM 2.5 average and the non-HDL-C level, but not the LDL-C level. Similar mediation effects (19%–91%) of the sphingolipids were also observed in 30-day time window. Conclusions: Our results suggest that sphingolipids may mediate the proatherogenic effects of short- and medium-term PM 2.5 exposure.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

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confidence: 99%

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Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids

Wang

Gong

et al. 2022

ATVB

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“…Air pollution has been shown to be both a contributing factor to asthma development (Wright and Brunst, 2013) and asthma exacerbations (Guarnieri and Balmes, 2014). Diesel exhaust has been shown to a major player in the environmental influences of asthma and diesel exhaust particles have been shown to upregulate both ceramide production and sphingosine kinase 1 (SphK1) activity in bronchial epithelial cells (Shaheen et al, 2016). Inhalation of carbonaceous pollutants in the form of carbon nanoparticles has also been linked to pulmonary dysfunction and exposure to these xenobiotic agents has been shown to alter ceramide accumulation in lung epithelial cells leading to aberrant inflammatory response generation in the lung (Peuschel et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Sphingolipids and their enigmatic role in asthma

Sturgill

2018

Advances in Biological Regulation

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Asthma is defined as a chronic inflammatory condition in the lung and is characterized by episodic shortness of breath with expiratory wheezing and cough. Asthma is a serious public health concern globally with an estimated incidence over 300 million. Asthma is a complex disease in that it manifests as disease of gene and environmental interactions. Sphingolipids are a unique class of lipids involved in a host of biological functions ranging from serving as key cellular membrane lipids to acting as critical signaling molecules. To date sphingolipids have been studied across various human conditions ranging from neurological disorders to cancer to infection to autoimmunity. This review will focus on the role of sphingolipids in asthma development and pathology with particular focus on the role of mast cell sphingolipid biology.

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“…DE was produced by same procedure as described in the previous paper (Shaheen et al, 2016). A four-cylinder 2179-cc diesel engine (Isuzu Motors, Tokyo, Japan) was operated at a speed of 1500 rpm and 80% load with diesel fuel.…”

Section: Diesel Exhaustmentioning

confidence: 99%

Comprehensive analysis of the alteration of plasma miRNA expression level in mice exposed to diesel exhaust

Tachibana

Kodaira

Kuroiwa

et al. 2021

Fundam. Toxicol. Sci.

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MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides in length that play important roles in controlling a huge range of eukaryotic cell functions. Many studies have shown that abnormal expression levels of miRNAs are associated with many diseases and detrimental health effects caused by exposure to environmental pollutants and particulate matter. As a number of reports suggest that profiles of miRNAs in body fluids reflect physiological and pathological status, extracellular miRNAs, especially in plasma and serum, are being focused on as candidate disease biomarkers. Although these phenomena suggest that expression levels of plasma miRNAs can also be used as biomarkers for the detection of adverse health effects caused by exposure to environmental pollutants, there are still few studies on this subject. In the present study, we used diesel exhaust (DE) and filtered-DE (F-DE), which is DE with the particulate matter removed, as a model for environmental pollutant exposure and comprehensively analyzed alteration of the expression levels of plasma miRNAs in mice using a LNA miRNA microarray. MiRNA microarray analyses showed altered expression level of 5 plasma miRNAs (miR-1983, miR-720, miR-1957, miR-335-3p, and miR-1897-5p) in the DE-exposed group and F-DEexposed group. The results show both the possibility that exposure to various environmental chemicals including DE alters plasma miRNAs and the potential for plasma miRNAs to be used as biomarkers of exposure to these chemicals.

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The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice

Cited by 13 publications

References 62 publications

Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids

Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids

Sphingolipids and their enigmatic role in asthma

Comprehensive analysis of the alteration of plasma miRNA expression level in mice exposed to diesel exhaust

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