Human Serum Albumin Cys34 Adducts in Newborn Dried Blood Spots: Associations With Air Pollution Exposure During Pregnancy

Background: Increasing evidence suggests that exposure to air pollution during pregnancy is associated with adverse pregnancy outcomes. However, biomarkers associated with air pollution exposure are widely lacking and often transient. In addition, ascertaining biospecimens during pregnacy to assess the prenatal environment remains largely infeasible.Objectives: To address these challenges, we investigated relationships between air pollution exposure during pregnancy and human serum albumin Cys34 (HSA-Cys34) adducts in newborn dried blood spots (DBS) samples, which captures an integration of perinatal exposures to small reactive molecules in circulating blood.Methods: Newborn DBS were obtained from a state archive for a cohort of 120 children born at one Kaiser Permanente Southern California (KPSC) hospitals in 2007. These children were selected to maximize the range of residential air pollution exposure during the entire pregnancy to PM2.5, PM10, NO2, O3, based on monthly estimates interpolated from regulatory monitoring sites. HSA-Cys34 adducts were selected based on previously reported relationships with air pollution exposure and oxidative stress.Results: Six adducts measured in newborn DBS samples were associated with air pollution exposures during pregnancy; these included direct oxidation products, adducts formed with small thiol compounds, and adducts formed with reactive aldehydes. Two general trends were identified: Exposure to air pollution late in pregnancy (i.e., in the last 30 days) was associated with increased oxidative stress, and exposure to air pollution earlier in pregnancy (i.e., not in the last 30 days) was associated with decreased oxidative stress around the time of birth.Discussion: Air pollution exposure occurring during pregnancy can alter biology and leave measurable impacts on the developing infant captured in the newborn DBS adductome, which represents a promising tool for investigating adverse birth outcomes in population-based studies.

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Air pollution-induced placental alterations: an interplay of oxidative stress, epigenetics, and the aging phenotype?

Clinical Epigenetics ◽

10.1186/s13148-019-0688-z ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 16

Author(s):

N. D. Saenen ◽

D. S. Martens ◽

K. Y. Neven ◽

R. Alfano ◽

H. Bové ◽

...

Keyword(s):

Oxidative Stress ◽

Air Pollution ◽

Energy Metabolism ◽

Early Life ◽

Nitrosative Stress ◽

Later Life ◽

Modes Of Action ◽

Air Pollution Exposure ◽

Exposure During Pregnancy ◽

Pollution Exposure

Abstract According to the “Developmental Origins of Health and Disease” (DOHaD) concept, the early-life environment is a critical period for fetal programming. Given the epidemiological evidence that air pollution exposure during pregnancy adversely affects newborn outcomes such as birth weight and preterm birth, there is a need to pay attention to underlying modes of action to better understand not only these air pollution-induced early health effects but also its later-life consequences. In this review, we give an overview of air pollution-induced placental molecular alterations observed in the ENVIRONAGE birth cohort and evaluate the existing evidence. In general, we showed that prenatal exposure to air pollution is associated with nitrosative stress and epigenetic alterations in the placenta. Adversely affected CpG targets were involved in cellular processes including DNA repair, circadian rhythm, and energy metabolism. For miRNA expression, specific air pollution exposure windows were associated with altered miR-20a, miR-21, miR-146a, and miR-222 expression. Early-life aging markers including telomere length and mitochondrial DNA content are associated with air pollution exposure during pregnancy. Previously, we proposed the air pollution-induced telomere-mitochondrial aging hypothesis with a direct link between telomeres and mitochondria. Here, we extend this view with a potential co-interaction of different biological mechanisms on the level of placental oxidative stress, epigenetics, aging, and energy metabolism. Investigating the placenta is an opportunity for future research as it may help to understand the fundamental biology underpinning the DOHaD concept through the interactions between the underlying modes of action, prenatal environment, and disease risk in later life. To prevent lasting consequences from early-life exposures of air pollution, policy makers should get a basic understanding of biomolecular consequences and transgenerational risks.

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Oxidative stress and air pollution exposure during pregnancy

Human & Experimental Toxicology ◽

10.1177/0960327114559992 ◽

2014 ◽

Vol 34 (8) ◽

pp. 838-847 ◽

Cited By ~ 24

Author(s):

S Nagiah ◽

A Phulukdaree ◽

D Naidoo ◽

K Ramcharan ◽

RN Naidoo ◽

...

Keyword(s):

Oxidative Stress ◽

Air Pollution ◽

Stress Response ◽

Oxidative Stress Response ◽

Air Pollutant ◽

Dna Integrity ◽

Mitochondrial Depolarization ◽

Air Pollution Exposure ◽

Exposure During Pregnancy ◽

Pollution Exposure

Chronic air pollution exposure during pregnancy can cause oxidative stress leading to adverse birth outcomes. The aim of this study was to assess and compare oxidative stress response in peripheral lymphocytes isolated from pregnant women from a highly industrialized locale (south Durban (SD); n = 50) and a control with lower air pollutant levels (north Durban (ND); n = 50). Oxidative stress response was measured by quantifying malondialdehyde (MDA) levels and a SuperArray gene panel. Mitochondrial function (adenosine triphosphate (ATP) levels and mitochondrial depolarization), DNA integrity (comet assay and mitochondrial DNA (mtDNA) viability) and DNA repair (OGG1) were assessed. Antioxidant response was assessed by quantification of glutathione (GSH) and SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2) and uncoupling protein 2 (UCP2) protein and messenger RNA (mRNA) expression. Levels of MDA ( p = 0.9), mitochondrial depolarization ( p = 0.88), ATP (1.89-fold), SOD2 (1.23-fold) and UCP2 (1.58-fold) gene expression were elevated in the SD group with significantly higher UCP2 protein levels ( p = 0.05) and longer comet tail length ( p = 0.0004). The expression of Nrf2 protein ( p = 0.03) and mRNA levels (−1.37-fold), GSH concentration ( p < 0.0001), mtDNA amplification (−2.04-fold) and OGG1 mRNA (−2.78-fold) activity were decreased in the SD group. Of the 84 oxidative stress-related genes evaluated, 26 were differentially regulated. Pregnant women exposed to higher air pollutant levels showed increased markers for oxidative stress and compromised DNA integrity and repair.

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Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations

Antioxidants ◽

10.3390/antiox10030474 ◽

2021 ◽

Vol 10 (3) ◽

pp. 474 ◽

Cited By ~ 1

Author(s):

Carolina Luna ◽

Alexis Arjona ◽

Carmen Dueñas ◽

Mario Estevez

Keyword(s):

Oxidative Stress ◽

Plasma Concentration ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Typical Feature ◽

Advanced Glycation ◽

Chemical Mechanisms ◽

Fasting Plasma ◽

Insight Into

Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed.

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Childhood cancer and traffic-related air pollution exposure in pregnancy and early life

ISEE Conference Abstracts ◽

10.1289/isee.2013.p-2-06-06 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 3811

Author(s):

Julia Heck ◽

Jun Wu ◽

Christina Lombardi ◽

Travis Meyers ◽

Michelle Wilhelm ◽

...

Keyword(s):

Air Pollution ◽

Childhood Cancer ◽

Early Life ◽

Air Pollution Exposure ◽

Pollution Exposure ◽

In Pregnancy

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Fine particulate matter (PM2.5) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00881.2020 ◽

2021 ◽

Author(s):

Bradford G. Hill ◽

Benjamin Rood ◽

Amanda Ribble ◽

Petra Haberzettl

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Air Pollution ◽

Vascular Inflammation ◽

Fine Particulate Matter ◽

Cvd Risk ◽

Vegf Signaling ◽

Fine Particulate ◽

Air Pollution Exposure ◽

Pollution Exposure

Fine particulate matter (PM2.5) air pollution exposure increases the risk of developing cardiovascular disease (CVD). Although the precise mechanisms by which air pollution exposure increases CVD risk remain uncertain, research indicates that PM2.5-induced endothelial dysfunction contributes to the CVD risk. Previous studies demonstrate that concentrated PM2.5 (CAP) exposure induces vascular inflammation and impairs insulin and VEGF signaling dependent upon pulmonary oxidative stress. To assess whether CAP exposure induces these vascular effects via plasmatic factors, we incubated aortas from naïve mice with plasma isolated from mice exposed to HEPA-filtered air or CAP (9 d) and examined vascular inflammation and insulin and VEGF signaling. We found that treatment of naïve aortas with plasma from CAP-exposed mice activates NF-κBα and induces insulin and VEGF resistance, indicating transmission by plasmatic factor(s). To identify putative factors, we exposed lung-specific ecSOD-transgenic (ecSOD-Tg) mice and wildtype (WT) littermates to CAP at concentrations of either ~60 µg/m3 (CAP60) or ~100 µg/m3 (CAP100) and measured the abundance of plasma metabolites by mass spectrometry. In WT mice, both CAP concentrations increased levels of fatty acids such as palmitate, myristate, and palmitoleate and decreased numerous phospholipid species; however, these CAP-induced changes in the plasma lipidome were prevented in ecSOD-Tg mice. Consistent with the literature, we found that fatty acids such as palmitate are sufficient to promote endothelial inflammation. Collectively, our findings suggest that PM2.5 exposure, by inducing pulmonary oxidative stress, promotes unique lipidomic changes characterized by high levels of circulating fatty acids, which are sufficient to trigger vascular pathology.

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