Hydrogen Peroxide-Induced VCAM-1 Expression in Pancreatic Islets and β-Cells Through Extracellular Ca2+ Influx

Lee, Sukmook; Ha, In Su; Kim, Jae Hyun; Park, Kyong Soo; Han, Kyu Hyun; Kim, Sun‐Hee; Chae, Young Chan; Kim, Sun Hee; Kim, Yun Hee; Suh, Pann‐Ghill; Ryu, Sung Ho; Kim, Jung-Eun; Bang, Kitae; Hwang, Jong Ik; Yang, Jaeseok; Park, Kwang-Wook; Chung, Junho; Ahn, Curie

doi:10.1097/tp.0b013e318188ab04

Cited by 11 publications

(6 citation statements)

References 60 publications

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“…The working H 2 O 2 concentration was chosen from a survey curve of β TC3 cells treated with different H 2 O 2 concentrations ranging from 0 to 600 μ M. The IC 50 concentration of 70 μ M was used in this experiment as stressor agent for the β TC3 cells. Other previously published articles on β -pancreatic cells have used H 2 O 2 in the range 200–400 μ M [29, 30]. …”

Section: Resultsmentioning

confidence: 99%

Chokeberry Anthocyanin Extract as Pancreaticβ-Cell Protectors in Two Models of Induced Oxidative Stress

Rugină

Diaconeasa

Coman

et al. 2015

Oxidative Medicine and Cellular Longevity

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The aim of this study was to investigate the protective effects of a chokeberry anthocyanin extract (CAE) on pancreatic β-cells (βTC3) exposed to hydrogen peroxide- (H2O2-) and high glucose- (HG-) induced oxidative stress conditions. In order to quantify individual anthocyanins high performance liquid chromatography (HPLC) coupled to photodiode array (PDA) was used. The identification of the fragment ion pattern of anthocyanins was carried out by electrospray ionization mass spectrometry (LC-ESI-MS). The results showed that physiologically achievable concentrations of CAE (1, 5, and 10 μM) protect βTC3 against H2O2- and HG-induced cytotoxicity. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were increased in pancreatic β-cells pretreated with CAE compared to cells exposed to the prooxidant agents. GSH levels initially reduced after exposure to H2O2 and HG were restored by pretreatment with CAE. Insulin secretion in βTC3 cells was enhanced by CAE pretreatment. CAE restored the insulin pool and diminished the intracellular reactive oxygen species level in glucose-induced stress condition in βTC3 cells. These results demonstrate that anthocyanins from CAE were biologically active, showing a secretagogue potential and an antioxidative protection of enzymatic systems, conferring protection against H2O2 and glucose toxicity in βTC3 cells.

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Section: Resultsmentioning

confidence: 99%

Chokeberry Anthocyanin Extract as Pancreaticβ-Cell Protectors in Two Models of Induced Oxidative Stress

Rugină

Diaconeasa

Coman

et al. 2015

Oxidative Medicine and Cellular Longevity

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“…It has also been previously reported that H 2 O 2 can alter β2- integrin CD11b/CD18-activation and enhance neutrophil adhesion (39). Furthermore, H 2 O 2 has been described to induce VCAM-1 expression in B cells through extracellular Ca 2+ influx (40) and enhance leukocyte adhesion to endothelial cells via NFκβ dependent gene regulation of VCAM-1 (41). Our experiments (data not shown) revealed that H 2 O 2 had no effect upon either basal or TCR-stimulated adhesion to fibronectin nor on expression of the integrin receptors, LFA-1 (CD11a expression) and α4β1 (CD49d expression) in SEB-activated T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration

Ball

Vlisidou

Blunt

et al. 2017

The Journal of Immunology

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H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H2O2-induced chemotaxis deficiency. We hypothesize that although H2O2 serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process.

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“…In contrast, a significant induction for inflammatory cytokines including IL‐1ß and IL‐6 and adhesion molecules such as VCAM‐1 and P‐selectin was observed after BD induction in our study, corroborating the finding that donor BD itself leads to an inflammatory response in organs 23, 44, 45 (Figure 1). For instance, enhanced expression of VCAM‐1 in human pancreatic cancers has suggested a role of this marker in tumor pathogenesis, and enhanced P‐selectin expression has been attributed to acute pancreatitis 46, 47, 48.…”

Section: Discussionmentioning

confidence: 99%

Treatment With Tetrahydrobiopterin Overcomes Brain Death–Associated Injury in a Murine Model of Pancreas Transplantation

Oberhuber

Ritschl

Fabritius

et al. 2015

American Journal of Transplantation

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Brain death (BD) has been associated with an immunological priming of donor organs and is thought to exacerbate ischemia reperfusion injury (IRI). Recently, we showed that the essential nitric oxide synthase co‐factor tetrahydrobiopterin (BH4) abrogates IRI following experimental pancreas transplantation. We therefore studied the effects of BD in a murine model of syngeneic pancreas transplantation and tested the therapeutic potential of BH4 treatment. Compared with sham‐operated controls, donor BD resulted in intragraft inflammation reflected by induced IL‐1ß, IL‐6, VCAM‐1, and P‐selectin mRNA expression levels and impaired microcirculation after reperfusion (p < 0.05), whereas pretreatment of the BD donor with BH4 significantly improved microcirculation after reperfusion (p < 0.05). Moreover, BD had a devastating impact on cell viability, whereas BH4‐treated grafts showed a significantly higher percentage of viable cells (p < 0.001). Early parenchymal damage in pancreatic grafts was significantly more pronounced in organs from BD donors than from sham or non‐BD donors (p < 0.05), but BH4 pretreatment significantly ameliorated necrotic lesions in BD organs (p < 0.05). Pretreatment of the BD donor with BH4 resulted in significant recipient survival (p < 0.05). Our data provide novel insights into the impact of BD on pancreatic isografts, further demonstrating the potential of donor pretreatment strategies including BH4 for preventing BD‐associated injury after transplantation.

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Hydrogen Peroxide-Induced VCAM-1 Expression in Pancreatic Islets and β-Cells Through Extracellular Ca2+ Influx

Abstract: An extracellular calcium-dependent H2O2 pathway is the critical mediator of VCAM-1 expression by pancreatic islets and beta-cells. Inhibition of this pathway by catalase overexpression in donor islets can be exploited to protect against xenoislet immune responses.

Cited by 11 publications

References 60 publications

Chokeberry Anthocyanin Extract as Pancreaticβ-Cell Protectors in Two Models of Induced Oxidative Stress

Chokeberry Anthocyanin Extract as Pancreaticβ-Cell Protectors in Two Models of Induced Oxidative Stress

Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration

Treatment With Tetrahydrobiopterin Overcomes Brain Death–Associated Injury in a Murine Model of Pancreas Transplantation

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