Multidrug resistance-associated protein 2 is negatively regulated by oxidative stress in rat intestine via a posttranslational mechanism. Impact on its membrane barrier function

Introduction: Shear stress forces play an integral role in dictating the endothelial cell (EC) response to changes in blood flow, pro-inflammatory response and hence development of atherosclerosis. Previously, our group has identified EC microRNA-155 (miR-155) as one of the key signature dysregulated miRNAs in areas of chronic low magnitude oscillatory shear stress (OSS) in vasculature and OSS models of in-vitro. Hypothesis: we hypothesized that acute induction of OSS mediates EC oxidative stress, inflammation and dysfunction, via dysregulation of EC miR-155. Methods: 12-week old C57B/6J mice were subjected to abdominal aortic coarctation (AAC), a unique model of acute induction of OSS, for 3 days and downstream segments of acute OSS were compared to upstream unidirectional shear stress (USS) segments of the thoracic aorta. Results: Acute OSS resulted in down regulation of EC miR-155 expression and inverse upregulation of EC RhoA and Myosin light chain kinase (MYLK), known targets of miR-155-mediated EC cytoskeleton organization, in OSS segments compared with USS. This was associated with impaired EC dependent relaxation, differential contractile response to phenylephrine, and loss of EC barrier function as evaluated by extravasation of Evans-blue dye assay. In parallel, En-face immunohistochemical staining also showed increased expression of EC nitric oxide synthase (eNOS) along with increased levels of reactive oxygen species (ROS) and nitrotyrosine (NY) formation in OSS segments compared with USS. Conclusions: Together, our studies shed light on the early changes in EC response to acute induction of OSS and resulting down-regulation of EC mir-155, including; oxidative/inflammatory stress, EC dysfunction, loss of barrier function and cytoskeletal changes. Despite the early upregulation of eNOS, it could also potentially synergize with the activation of the RhoA-MYLK pathway in EC oxidative (ROS/NY)/inflammatory stress and associated EC dysfunction. Further studies are in progress to dissect the interplay between these different pathways and their causal relationships as downstream targets of EC miR-155.

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Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging

International Journal of Molecular Sciences ◽

10.3390/ijms19113349 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3349 ◽

Cited By ~ 3

Author(s):

Jin Namkoong ◽

Dale Kern ◽

Helen Knaggs

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Human Skin ◽

Barrier Function ◽

Skin Barrier ◽

Skin Aging ◽

Skin Barrier Function ◽

Oxidative Stress Biomarkers ◽

Stress Biomarkers ◽

And Oxidative Stress

Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, Saccharomyces cerevisiae and Rhodiola rosea root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of Narcissus tazetta bulb extract and Schisandra chinensis fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.

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The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress

Journal of Neurochemistry ◽

10.1046/j.1471-4159.2001.00101.x ◽

2001 ◽

Vol 76 (2) ◽

pp. 627-636 ◽

Cited By ~ 113

Author(s):

Johannes Hirrlinger ◽

Jörg König ◽

Dietrich Keppler ◽

Jörg Lindenau ◽

Jörg B. Schulz ◽

...

Keyword(s):

Oxidative Stress ◽

Multidrug Resistance ◽

Multidrug Resistance Protein ◽

Glutathione Disulfide ◽

Rat Astrocytes ◽

Resistance Protein

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Repression of TXNIP-NLRP3 axis restores intestinal barrier function via inhibition of myeloperoxidase activity and oxidative stress in nonalcoholic steatohepatitis

Journal of Cellular Physiology ◽

10.1002/jcp.27513 ◽

2018 ◽

Vol 234 (5) ◽

pp. 7524-7538 ◽

Cited By ~ 7

Author(s):

Ru-Xue Bai ◽

Ying-Ying Xu ◽

Geng Qin ◽

Yan-Ming Chen ◽

Hui-Fen Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Nonalcoholic Steatohepatitis ◽

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Myeloperoxidase Activity ◽

And Oxidative Stress

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Effects of Dietary Taurine Supplementation to Gilts during Late Gestation and Lactation on Offspring Growth and Oxidative Stress

Animals ◽

10.3390/ani9050220 ◽

2019 ◽

Vol 9 (5) ◽

pp. 220 ◽

Cited By ~ 2

Author(s):

Mengmeng Xu ◽

Long Che ◽

Kaiguo Gao ◽

Li Wang ◽

Xuefen Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Growth Performance ◽

Barrier Function ◽

Average Daily Gain ◽

Basal Diet ◽

Intestinal Morphology ◽

Late Gestation ◽

Villus Height ◽

And Oxidative Stress

Birth is one of the most important events of animal production agriculture, as newborns are abruptly forced to adapt to environmental and nutritional disruptions that can lead to oxidative damage and delay in growth. Taurine (Tau) is an important regulator of oxidative stress and possesses growth-enhancing properties. In the present study, we investigated the effects of dietary Tau supplementation in gilts during late gestation and lactation on the growth performance of piglets by assessing intestinal morphology and barrier function, and oxidative stress status. Sixteen gilts were randomly allocated to the Con (basal diet) and Tau (basal diet with 1% Tau) groups from 75 d of gestation to weaning. Maternal dietary Tau supplementation significantly increased weaning weight and average daily gain weight in piglets. Piglets in the Tau group had higher villus height and villus height-to-crypt depth ratio (VCR), ZO-1 protein expression, and secretory immunoglobulin A (sIgA) content in the jejunum. Meanwhile, Tau bebeficial affected the milk quality of gilts, as indicated by decreased malondialdehyde (MDA) concentration and increased total superoxide dismutase (T-SOD), total antioxidative capability (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activity. Furthermore, Tau supplementation increased T-SOD activity in plasma and SOD2 protein expression in the jejunum in the piglets. In conclusion, this study provides evidence that dietary Tau supplementation to gilts improves growth performance in piglets, owing to improved intestinal morphology and barrier function, as well as inhibition of oxidative stress.

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Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

Nutrients ◽

10.3390/nu11102271 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2271 ◽

Cited By ~ 4

Author(s):

Massimiliano G. Bianchi ◽

Martina Chiu ◽

Giuseppe Taurino ◽

Furio Brighenti ◽

Daniele Del Rio ◽

...

Keyword(s):

Oxidative Stress ◽

Barrier Function ◽

Cell Model ◽

Intestinal Cell ◽

Epithelial Barrier ◽

Epithelial Barrier Function ◽

Inflammatory Stress ◽

Cell Monolayers ◽

Dietary Polyphenols ◽

Junctional Proteins

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level.

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