Heme Oxygenase-1 Protects Pancreatic β Cells from Apoptosis Caused by Various Stimuli

Tobiasch, Edda; Günther, Lukas; Bach, Fritz H.

doi:10.2310/6650.2001.33721

Cited by 88 publications

(56 citation statements)

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“…Besides, HO-1 also contributes to cytoprotection by reducing apoptosis. Tobiasch et al demonstrated that CoPPinduced βTC3 cells (an insulinoma cell line) with high HO-1 levels were able to counteract the apoptosis of beta cells caused by various stimuli through activation of the p38 mitogen-activated protein kinase pathway [40]. Our TUNEL assay data apparently support those findings.…”

Section: Discussionsupporting

confidence: 84%

Transgenic expression of haem oxygenase-1 in pancreatic beta cells protects non-obese mice used as a model of diabetes from autoimmune destruction and prolongs graft survival following islet transplantation

Huang

Chu²,

Yu³

et al. 2010

Diabetologia

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Aims/hypothesis Haem oxygenase 1 (HO-1) has strong anti-apoptotic, anti-inflammatory and antioxidative effects that help protect cells against various forms of immune attack. We investigated whether transgenic expression of Ho-1 (also known as Hmox1) in pancreatic beta cells would protect NOD mice from autoimmune damage and prolong graft survival following islet transplantation. Methods To evaluate the protective effect of beta cellspecific HO-1 in autoimmune diabetes, we used an insulin promoter-driven murine Ho-1 construct (pIns-mHo-1) to generate a transgenic NOD mouse. Transgene expression, insulitis and the incidence of diabetes in mice were characterised. Lymphocyte composition, the development of T helper (Th)1, Th2 and T regulatory (Treg) cells, T cell proliferation and lymphocyte-mediated disease transfer were analysed. The potential effects of transgenic islets and islet transplantation on apoptosis, inflammation and the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) were evaluated. Results Transgenic mice showed less severe insulitis and a lower incidence of diabetes than non-transgenic control littermates. Lymphocyte composition and functions were not affected. Islets from transgenic mice expressed lower levels of proinflammatory cytokines/chemokines, proapoptotic gene expression and amounts of ROS/RNS, and were more resistant to TNF-α-and IFN-γ-induced apoptosis. Islet grafts from transgenic mice also survived longer in diabetic recipients than control islets. Conclusions/interpretation Transgenic overexpression of Ho-1 in beta cells protected NOD mice from diabetes and delayed the autoimmune destruction of islet grafts, providing valuable insight into the development of better strategies for clinical islet transplantation in patients with type 1 diabetes.

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Section: Discussionsupporting

confidence: 84%

Transgenic expression of haem oxygenase-1 in pancreatic beta cells protects non-obese mice used as a model of diabetes from autoimmune destruction and prolongs graft survival following islet transplantation

Huang

Chu²,

Yu³

et al. 2010

Diabetologia

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“…Among the genes induced by IL-1β and supraphysiological glucose concentrations, the transcription factor c-Myc stimulates apoptosis more than proliferation in rodent beta cells [21][22][23], whereas the antioxidant enzyme haeme-oxygenase 1 (HO1) improves beta cell survival under various stressful conditions [17,[24][25][26]. In vitro, overnight culture of rat islets in the presence of 30 mmol/l glucose (G30) instead of 10 mmol/l glucose (G10) markedly stimulated expression of HO1 and c-Myc at the mRNA and protein levels in a Ca 2+ -and cyclic AMP-dependent manner without affecting c-Myc or HO1 mRNA stability [27,28].…”

Section: Introductionmentioning

confidence: 99%

High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NF?B

et al. 2005

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Aims/hypothesis: Hyperglycaemia and the proinflammatory cytokine IL-1β induce similar alterations of beta cell gene expression, including up-regulation of c-Myc and haeme-oxygenase 1. These effects of hyperglycaemia may result from nuclear factor-kappa B (NFκB) activation by oxidative stress. To test this hypothesis, we compared the effects of IL-1β, high glucose, and hydrogen peroxide, on NFκB DNA binding activity and target gene mRNA levels in cultured rat islets. Methods: Rat islets were precultured for 1 week in serum-free RPMI medium ontaining

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“…HO-1 upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo, HO-1 upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents (Pileggi et al, 2001;Tobiasch et al, 2001).…”

Section: Scavenging-free Radicalsmentioning

confidence: 99%

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Hui

Dotta

Mario

et al. 2004

Journal Cellular Physiology

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The homeostatic control of beta-cell mass in normal and pathological conditions is based on the balance of proliferation, differentiation, and death of the insulinsecreting cells. A considerable body of evidence, accumulated during the last decade, has emphasized the significance of the disregulation of the mechnanisms regulating the apoptosis of beta-cells in the sequence of events that lead to the development of diabetes. The identification of agents capable of interfering with this process needs to be based on a better understanding of the beta-cell specific pathways that are activated during apoptosis. The aim of this article is fivefold: (1) a review of the evidence for beta-cell apoptosis in Type I diabetes, Type II diabetes, and islet transplantation, (2) to review the common stimuli and their mechanisms in pancreatic beta-cell apoptosis, (3) to review the role of caspases and their activation pathway in beta-cell apoptosis, (4) to review the caspase cascade and morphological cellular changes in apoptotic beta-cells, and (5) to highlight the putative strategies for preventing pancreatic beta-cells from apoptosis.

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Heme Oxygenase-1 Protects Pancreatic β Cells from Apoptosis Caused by Various Stimuli

Cited by 88 publications

References 50 publications

Transgenic expression of haem oxygenase-1 in pancreatic beta cells protects non-obese mice used as a model of diabetes from autoimmune destruction and prolongs graft survival following islet transplantation

Transgenic expression of haem oxygenase-1 in pancreatic beta cells protects non-obese mice used as a model of diabetes from autoimmune destruction and prolongs graft survival following islet transplantation

High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NF?B

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

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