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- Hayderi, A., 1990-, et al.
(författare)
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Interferon gamma reprograms glutamine metabolic pathways in human aortic smooth muscle cells
- 2023
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 379:Suppl. 1, s. S8-S8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Cells within atherosclerotic lesions have a higher glutamine demand than cells in healthy vessel although glutaminase, the enzyme converting glutamine to glutamate, is significantly downregulated in human carotid lesions. This may suggest rewiring of glutamine metabolic pathways in atherosclerotic lesions, caused by infiltrating immune cells and or their cytokines. Here we aimed at exploring the enzymes and transporters involved in glutamine metabolism in human carotid atherosclerotic tissues and aortic smooth muscle cells (hAoSMCs) exposed to interferon gamma.Methods: Protein and mRNA from interferon gamma-treated hAoSMCs were subjected to Western blot or qRT-PCR for quantification of enzymes and transporters involved in glutamine metabolism. H2DCFDA probe was utilized for detection of intracellular reactive oxygen species (ROS) using flow cytometry. The expression of these enzymes and transporters was also evaluated in human carotid lesions (GEO accession: GSE43292).Results: Interferon-treated hAoSMCs display a significantly lower expression of glutaminase followed by an increase in the expression of glutamine transporters, glutamine synthetase and glutamine-fructose-6-phosphate transaminase-1 (GFPT1). The level of ROS and the expression of enzymes involved in de novo synthesis of glutathione are elevated in interferon-treated cells. A similar expression pattern for these genes, expect for GFPT1, is also evident in human carotid lesions where glutaminase mRNA shows a strong positive correlation with SMC markers and a strong negative correlation with macrophage markers.Conclusions: Glutamine metabolism is disrupted in human carotid lesions and interferon gamma alters glutamine metabolism in hAoSMCs, which may favor the production of UDP-GlcNAc and reactive oxygen species.
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- Lind, Monica P., et al.
(författare)
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Circulating levels of persistent organic pollutants are related to retrospective assessment of life-time weight change
- 2013
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 90:3, s. 998-1004
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent organic pollutants (POPs) have been suggested to be linked to obesity. We have previously shown that less-chlorinated PCBs were positively related to fat mass, while highly-chlorinated PCBs were inversely related to obesity.Objective: The aim of the present evaluation is to investigate the relationship between retrospective assessed life-time change in body weight (20-70. years) with circulating POP levels measured at age 70. years.Methods: 1016 subjects aged 70. years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUSs) study. 16 PCBs and 3 OC pesticides were analyzed using HRGC/HRMS. Current body weight was measured and participants self-reported their weight at age 20.Results: The average estimated weight change over 50. years was 14.4. kg. Both the sum of OC pesticide concentrations (4.3. kg more weight gain in quintile 5 vs. quintile 1, p< 0.0001) and the sum of the less-chlorinated PCBs were positively related to the estimated weight change (3.7. kg more weight gain in quintile 2 vs. quintile 1, non-linear relationship p=0.0015). In contrast, the sum of concentrations of highly-chlorinated PCBs were inversely related to estimated weight change (8.4. kg less weight gain in quintile 5 vs. quintile 1, p< 0.0001).Conclusion: High levels of OC pesticides and the less-chlorinated PCBs at age 70 were associated with a pronounced estimated weight change over the previous 50. years. However, the opposite was seen for highly-chlorinated PCBs. Differences in mode of action, toxicokinetics, non-linear relationships and reverse causation might explain these discrepancies.
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- Lind, M., et al.
(författare)
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Results from two population-based studies showed many environmental contaminants to be related to diabetes
- 2023
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Ingår i: Toxicology Letters. - : Elsevier. - 0378-4274 .- 1879-3169. ; 66:Suppl. 1, s. S195-S195
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: In previous studies on environmental contaminants and diabetes only a limited number of contaminants have been evaluated. The aim with the present study is therefore to obtain a comprehensive picture of the relationships between a large number of environmental contaminants and prevalent diabetes.Methods: In 10 examination cycles in The National Health and Nutrition Examination Survey (NHANES) (1999–2017) altogether 116 different environmental contaminants were evaluated in the circulation or urine in relation to prevalent diabetes. Similar analyses were also performed in the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) study (n=1016, all aged 70 years, 50% women, 42 contaminants). The logistic regression models were adjusted for age, sex, race, education, BMI, alcohol intake, smoking and lipids.Results: In a meta-analysis of the 10 NHANES examinations, thirty-six contaminants were significantly related to prevalent diabetes. Those contaminants represent a number of different classes, such as metals, PCBs, dioxins, furans, pesticides, PFAS, phthalates, and phenols.Some of these relationships were inverse, such as lead, cadmium, mercury, barium, cesium and strontium, some PFAS and furans, as well as benzophenone-3. In the smaller PIVUS study (119 prevalent diabetes cases), significant relationships similar to NHANES were seen for some PCBs, p,p’-DDE and lead. PFHxS and PFOA, showed inverse relationships also in PIVUS. The same was seen for mercury and cadmium.Conclusions: Many environmental contaminants were related to diabetes in the NHANES study. Some of these relationships, mainly some metals and PFAS, were negative. Many of these results were similar in the smaller PIVUS study. These findings need be evaluated in prospective studies.
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