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19 pages, 2355 KB

Open AccessArticle

Oxidized Dietary Oil, High in Omega-3 and Omega-6 Polyunsaturated Fatty Acids, Induces Antioxidant Responses in a Human Intestinal HT29 Cell Line

by Tone-Kari Knutsdatter Østbye, John-Erik Haugen, Elin Merete Wetterhus, Silje Kristine Bergum and Astrid Nilsson

Nutrients 2022, 14(24), 5341; https://doi.org/10.3390/nu14245341 - 15 Dec 2022

Cited by 8 | Viewed by 4468

Abstract

When oxidized, dietary oils generate products which have the potential to cause adverse effects on human health. The objective of the study was to investigate whether lipid oxidation products in an oxidized dietary oil can be taken up in intestinal cells, induce antioxidant stress responses and potentially be harmful. The in vitro cell model HT29 was exposed to camelina oil with different extents of oxidation, or only 4-hydroxy-2-hexenal (HHE) or 4-hydroxy-2-nonenal (HNE). The cellular content of HHE increased with an increasing extent of oxidation of the camelina oil added to the cell’s growth media, whereas HNE did not show a similar trend. Deuterated HHE was taken up by the HT29 cells, with 140 µM HHE metabolized within 0.5–1 h. The low oxidation degree of the camelina oil increased the gene expression of antioxidant markers (GPX, ATF6, XBP1). The increase in the gene expression of SOD at medium oxidation levels of the oil might indicate different regulation mechanisms. Highly oxidized camelina oil and a low concentration of HHE, over time, induced SOD and catalase enzyme activity in HT29 cells. Oxidized camelina oil contains multiple oxidation products which can be responsible for the intracellular responses observed in HT29 cells, while HHE and HNE in combination with other oxidation products induce antioxidant defence responses. Full article

(This article belongs to the Section Lipids)

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13 pages, 2722 KB

Open AccessEditor’s ChoiceArticle

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

by Amy K. Hauck, Tong Zhou, Ambuj Upadhyay, Yuxiang Sun, Michael B. O’Connor, Yue Chen and David A. Bernlohr

Antioxidants 2020, 9(12), 1210; https://doi.org/10.3390/antiox9121210 - 1 Dec 2020

Cited by 21 | Viewed by 4425

Abstract

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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14 pages, 1579 KB

Open AccessArticle

Two Toxic Lipid Aldehydes, 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), Accumulate in Patients with Chronic Kidney Disease

by Christophe O. Soulage, Caroline C. Pelletier, Nans Florens, Sandrine Lemoine, Laurence Dubourg, Laurent Juillard and Fitsum Guebre-Egziabher

Toxins 2020, 12(9), 567; https://doi.org/10.3390/toxins12090567 - 3 Sep 2020

Cited by 43 | Viewed by 5654

Abstract

Lipid aldehydes originating from the peroxidation of n-3 and n-6 polyunsaturated fatty acids are increased in hemodialysis (HD) patients, a process already known to promote oxidative stress. However, data are lacking for patients with chronic kidney disease (CKD) before the initiation of HD. We prospectively evaluated the changes of plasma concentrations of two major lipid aldehydes, 4-HHE and 4-HNE, according to the decrease of glomerular filtration rate (GFR) in 40 CKD and 13 non-CKD participants. GFR was measured by inulin or iohexol clearance. Thus, 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) were quantitated in plasma by gas chromatography coupled with mass spectrometry and their covalent adducts on proteins were quantified by immunoblotting. On the one hand, 4-HHE plasma concentration increased from CKD stage I–II to CKD stage IV–V compared to non-CKD patients (4.5-fold higher in CKD IV–V, p < 0.005). On the other hand, 4-HNE concentration only increased in CKD stage IV–V patients (6.2-fold, p < 0.005). The amount of covalent adducts of 4-HHE on plasma protein was 9.5-fold higher in CKD patients than in controls (p < 0.005), while no difference was observed for 4-HNE protein adducts. Plasma concentrations of 4-HNE and 4-HHE are increased in CKD IV–V patients before the initiation of hemodialysis. Full article

(This article belongs to the Section Uremic Toxins)

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13 pages, 1224 KB

Open AccessArticle

Effects of Marine Oils, Digested with Human Fluids, on Cellular Viability and Stress Protein Expression in Human Intestinal Caco-2 Cells

by Cecilia Tullberg, Gerd Vegarud, Ingrid Undeland and Nathalie Scheers

Nutrients 2017, 9(11), 1213; https://doi.org/10.3390/nu9111213 - 4 Nov 2017

Cited by 6 | Viewed by 6241

Abstract

In vitro digestion of marine oils has been reported to promote lipid oxidation, including the formation of reactive aldehydes (e.g., malondialdehyde (MDA) and 4-hydroxy-2-hexenal (HHE)). We aimed to investigate if human in vitro digestion of supplemental levels of oils from algae, cod liver, and krill, in addition to pure MDA and HHE, affect intestinal Caco-2 cell survival and oxidative stress. Cell viability was not significantly affected by the digests of marine oils or by pure MDA and HHE (0–90 μM). Cellular levels of HSP-70, a chaperone involved in the prevention of stress-induced protein unfolding was significantly decreased (14%, 28%, and 14% of control for algae, cod and krill oil, respectively; p ≤ 0.05). The oxidoreductase thioredoxin-1 (Trx-1) involved in reducing oxidative stress was also lower after incubation with the digested oils (26%, 53%, and 22% of control for algae, cod, and krill oil, respectively; p ≤ 0.001). The aldehydes MDA and HHE did not affect HSP-70 or Trx-1 at low levels (8.3 and 1.4 μM, respectively), whilst a mixture of MDA and HHE lowered Trx-1 at high levels (45 μM), indicating less exposure to oxidative stress. We conclude that human digests of the investigated marine oils and their content of MDA and HHE did not cause a stress response in human intestinal Caco-2 cells. Full article

(This article belongs to the Special Issue Dietary Supplements)

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14 pages, 2751 KB

Open AccessArticle

N-3 Polyunsaturated Fatty Acids Decrease the Protein Expression of Soluble Epoxide Hydrolase via Oxidative Stress-Induced P38 Kinase in Rat Endothelial Cells

by Takashi Okada, Katsutaro Morino, Fumiyuki Nakagawa, Masashi Tawa, Keiko Kondo, Osamu Sekine, Takeshi Imamura, Tomio Okamura, Satoshi Ugi and Hiroshi Maegawa

Nutrients 2017, 9(7), 654; https://doi.org/10.3390/nu9070654 - 24 Jun 2017

Cited by 10 | Viewed by 6985

Abstract

N-3 polyunsaturated fatty acids (PUFAs) improve endothelial function. The arachidonic acid-derived metabolites (epoxyeicosatrienoic acids (EETs)) are part of the endothelial hyperpolarization factor and are vasodilators independent of nitric oxide. However, little is known regarding the regulation of EET concentration by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in blood vessels. Sprague-Dawley rats were fed either a control or fish oil diet for 3 weeks. Compared with the control, the fish oil diet improved acetylcholine-induced vasodilation and reduced the protein expression of soluble epoxide hydrolase (sEH), a key EET metabolic enzyme, in aortic strips. Both DHA and EPA suppressed sEH protein expression in rat aorta endothelial cells (RAECs). Furthermore, the concentration of 4-hydroxy hexenal (4-HHE), a lipid peroxidation product of n-3 PUFAs, increased in n-3 PUFA-treated RAECs. In addition, 4-HHE treatment suppressed sEH expression in RAECs, suggesting that 4-HHE (derived from n-3 PUFAs) is involved in this phenomenon. The suppression of sEH was attenuated by the p38 kinase inhibitor (SB203580) and by treatment with the antioxidant N-acetyl-L-cysteine. In conclusion, sEH expression decreased after n-3 PUFAs treatment, potentially through oxidative stress and p38 kinase. Mild oxidative stress induced by n-3 PUFAs may contribute to their cardio-protective effect. Full article

(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)

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15 pages, 1206 KB

Open AccessArticle

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

by Kohji Nagayama, Katsutaro Morino, Osamu Sekine, Fumiyuki Nakagawa, Atsushi Ishikado, Hirotaka Iwasaki, Takashi Okada, Masashi Tawa, Daisuke Sato, Takeshi Imamura, Yoshihiko Nishio, Satoshi Ugi, Atsunori Kashiwagi, Tomio Okamura and Hiroshi Maegawa

Nutrients 2015, 7(9), 8112-8126; https://doi.org/10.3390/nu7095381 - 21 Sep 2015

Cited by 9 | Viewed by 7617

Abstract

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of MCP-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon. Full article

(This article belongs to the Special Issue DHA for Optimal Health)

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