CXCL12 protects pancreatic β-cells from oxidative stress by a Nrf2-induced increase in catalase expression and activity

Dinić, Svetlana; Grdović, Nevena; Uskoković, Aleksandra; Đorđević, Miloš; Mihailović, Mirjana; Jovanović, Jelena Arambašić; Poznanović, Goran; Vidaković, Melita

doi:10.2183/pjab.92.436

Cited by 31 publications

(21 citation statements)

References 64 publications

(70 reference statements)

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“…Biochemical experiments indicated that knockdown of NRF2 could increase MDA concentration and decrease concentration of SOD, GSH and CAT, enhancing the effects of laminarin in MRC-5 cells. Numerous studies have proved the protective role of NRF2 against oxidation in various cell types, keratinocytes ( Madduma Hewage et al, 2016 ; Zheng et al, 2014 ), pancreatic β-cells ( Dinić et al, 2016 ), mesenchymal stem cells ( Loseva et al, 2012 ), amongst others, elevating SOD, GSH and CAT cellular concentration. Besides, up-regulation of NRF2 was accompanied with suppressed MDA level during the amelioration of oxidative damage ( Xie et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Lü

Liu

Zhai

et al. 2017

PeerJ

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Oxidative damage is a major cause of lung diseases, including pulmonary fibrosis. Laminarin is a kind of polysaccharide extracted from brown algae and plays vital roles in various biological processes. However, the functions and mechanisms of laminarin in pulmonary oxidative damage are poorly understood. This study aimed at investigating the protective effect of laminarin against pulmonary oxidative damage and underlying mechanisms. Human lung fibroblasts MRC-5 cells were treated with hydrogen peroxide to induce oxidative damage. Laminarin treatment was performed before or after hydrogen peroxide treatment, and then major indexes of oxidative damage, including superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT), were quantified by biochemical assays. The expression of oxidation-related factor, nuclear factor erythroid 2 like 2 (NRF2) was analyzed by qPCR, Western blot and immunofluorescence assay. NRF2 knockdown and overexpression were performed by cell transfection to reveal possible mechanisms. Results showed that laminarin treatment of 0.020 mg/mL for 24 h, especially the pre-treatment, could significantly relieve changes in SOD, MDA, GSH and CAT that were altered by hydrogen peroxide, and promote NRF2 mRNA (P < 0.001). NRF2 protein was also elevated by laminarin, and nuclear translocation was observed. Factors in NRF2 signaling pathways, including KEAP1, NQO1, GCLC and HO1, were all regulated by laminarin. Roles of NRF2 were tested, suggesting that NRF2 regulated the concentration of SOD, MDA, GSH and CAT, suppressed KEAP1, and promoted NQO1, GCLC and HO1. These findings suggested the protective role of laminarin against pulmonary oxidative damage, which might involve the regulation of NRF2 signaling pathways. This study provided information for the clinical application of laminarin to pulmonary diseases like pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Lü

Liu

Zhai

et al. 2017

PeerJ

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“…CXCL12 reduced inflammation in experimental autoimmune encephalomyelitis 38 . It protected b cells from death by promoting islet neovascularization, reduced oxidative stress, and increased cell survival in allogeneic and xenogeneic islet transplantation models [39][40][41][42] . Therefore, the significantly decreased CCL23 and increased CXCL12 levels observed in the CO group in our study suggested less inflammation in CO islets posttransplantation.…”

Section: Discussionmentioning

confidence: 99%

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

et al. 2019

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Stresses encountered during human islet isolation lead to unavoidable b-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, b-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less b-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

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“…On the other hand, after viral infection, ROS are produced from activated phagocytes [24], and they mediate cellular injury and activate inflammatory redox-dependent transcription factors, such as NF-κB, thereby perpetuating inflammation. The virus-mediated production of ROS or a reduction in an- tioxidants can have severe consequences, as β cells are more prone to oxidative damage than most other tissues [8]. Additionally, in T1D, the T cell-mediated autoimmune destruction of pancreatic β cells is secondary to the primary invasion by macrophages and dendritic cells into the islets.…”

Section: Discussionmentioning

confidence: 99%

“…Islets inherently contain only a fraction of enzymatic activity in comparison to the liver, which has the highest abundance of these enzymes [27]. However, β cells are particularly sensitive to ROS because they are low in free radical-quenching (antioxidant) enzymes such as CAT, GPx, and SOD [8]. Thus, the capability of oxidative stress to damage mitochondria and ultimately decrease insulin secretion is not surprising [28].…”

Section: Discussionmentioning

confidence: 99%

“…The other antioxidant enzymes include glutathione (GSH) reductase, GSH S-transferase, peroxiredoxin, thioredoxin, and thioredoxin reductase [7]. β Cells express low levels of the antioxidant enzymes SOD, CAT, and GPx, and thereby increase their susceptibility to oxidative stress [8]. Oxidative stress occurs when the generation of reactive oxygen species (ROS) overcomes the scavenging abilities of antioxidants, and it may be mediated by a genetic lack of antioxidant enzymes as well as environmental triggers like viral infections [9].…”

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confidence: 99%

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Association between Antioxidant Enzyme Activities and <b><i>Enterovirus</i></b>-Infected Type 1 Diabetic Children

et al. 2018

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Significance of the Study• This study revealed that children with type 1 diabetes (T1D) infected with Enterovirus (EV) show a marked decrease in glutathione peroxidase, superoxide dismutase, and catalase activity, and a noticeable elevation in C-reactive protein compared to noninfected diabetic children. Our results confirm an association of EV infection with the inflammation and β cell damage seen in T1D, and suggest that antioxidant supplementation can play a protective role. DOI: 10.1159/000486718Keywords Type 1 diabetes · Enterovirus · Antioxidant enzymes · Diabetic children Abstract Objective: To examine the effect of infection with Enterovirus (EV) in children with type 1 diabetes (T1D) on the activities of serum antioxidant enzymes in diabetic and nondiabetic controls. Subjects and Methods: Three hundred and eighty-two diabetic and 100 nondiabetic children were tested for EV RNA using reverse transcriptase (RT)-PCR. The activities of serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also estimated in diabetic patients infected with EV (T1D-EV+), those not infected with EV (T1D-EV-), and in nondiabetic controls. Results: The frequency of EV was higher in diabetic children (100/382; 26.2%) than in healthy controls (0/100). Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA 1c ) and C-reactive protein (CRP) were significantly higher but C-peptide was significantly lower in diabetic children than in controls. CRP levels were higher in the T1D-EV+ group than in the T1D-EV-group, and higher in all diabetic children than in nondiabetic controls. The activities of the antioxidant enzymes GPx, SOD, and CAT decreased significantly in diabetic children compared to in controls. Moreover, the activities of the enzymes tested were significantly reduced in the T1D-EV+ group compared to in the T1D-EVgroup. Conclusion: Our data indicate that EV infection correlated with a decrease in the activity of antioxidant enzymes in the T1D-EV+ group compared to in the T1D-EVgroup; this may contribute to β cell damage and increased inflammation.

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CXCL12 protects pancreatic β-cells from oxidative stress by a Nrf2-induced increase in catalase expression and activity

Cited by 31 publications

References 64 publications

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

Association between Antioxidant Enzyme Activities and <b><i>Enterovirus</i></b>-Infected Type 1 Diabetic Children

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