Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells

Ortega-Camarillo, Clara; Guzmán-Grenfell, Alberto Martı́n; García‐Macedo, Rebeca; Rosales‐Torres, Ana María; Ávalos-Rodrı́guez, Alejandro; Durán‐Reyes, Genoveva; Medina-Navarro, Rafael; Crúz, Miguel A.; Díaz‐Flores, Margarita; Kumate, J

doi:10.1007/s11010-006-0829-5

Cited by 47 publications

(35 citation statements)

References 39 publications

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“…Moreover, studies suggest that p53 might perform its senescence and pro-apoptotic functions by directly signalling the mitochondria and inducing cytochrome c release [23,24]. These data were confirmed by experiments showing p53 mobilisation to the mitochondrial membrane during oxidative stress induced by hyperglycaemia, leading to changes in mitochondrial membrane potential [25].…”

Section: Introductionmentioning

confidence: 72%

Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells

et al. 2011

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Aims/hypothesis Damage persists in HUVECs exposed to a constant high glucose concentration long after glucose normalisation, a phenomenon termed 'metabolic memory'. Evaluation of the effects of exposure of HUVECs to oscillating high glucose on the induction of markers of oxidative stress and DNA damage (phospho-γ-histone H2AX and PKCδ) and onset of metabolic memory, and the possible role of the tumour suppressor transcriptional factor p53 is of pivotal interest. Methods HUVECs were incubated for 3 weeks in 5 or 25 mmol/l glucose or oscillating glucose (24 h in 5 mmol/l glucose followed by 24 h in 25 mmol/l glucose) or for 1 week in constant 5 mmol/l glucose after being exposed for 2 weeks to continuous 25 mmol/l high glucose or oscillating glucose. Transcriptional activity of p53 was also evaluated in the first 24 h after high glucose exposure. Results High constant glucose upregulated phospho-γ-histone H2AX and protein kinase C (PKC)δ compared with control. Oscillating glucose was even more effective than both normal and constant high glucose. Both constant and oscillating glucose resulted in a memory effect, which was more pronounced in the oscillating condition. Transcriptional activity of p53 peaked 6 h after glucose exposure, showing a predicted oscillatory behaviour. Conclusions/interpretation Exposure to oscillating glucose was more deleterious than constant high glucose and induced a metabolic memory after glucose normalisation. Hyperactivation of p53 during glucose oscillation might be due to the absence of consistent feedback inhibition during each glucose spike and might account for the worse outcome of this condition.

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Section: Introductionmentioning

confidence: 72%

Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells

et al. 2011

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“…Also, hyperglycemia induces the generation of ROS and triggers pancreatic β-cell apoptosis (Robertson et al 2003;Kim et al 2005;Ortega-Camarillo et al 2006;Jonas et al 2009). Therefore, prevention of pancreatic β-cell apoptosis induced by hyperglycemia is an important therapeutic issue for diabetic and metabolic disease patients.…”

Section: Discussionmentioning

confidence: 99%

“…High glucose conditions have been implicated in the death of pancreatic β-cells (Efanova et al 1998;Kim et al 2005;Ortega-Camarillo et al 2006). To investigate the potential anti-apoptotic effect of SFH against high glucose conditions in vitro, we measured the percentage of apoptotic cells using flow cytometry analysis (FACS, Figure 2).…”

Section: Sfh Protects Rin5f Cells From Glucotoxicity-mediated Apoptosismentioning

confidence: 99%

Anti-apoptotic effects of silk fibroin hydrolysate in RIN5F cell on high glucose condition

Park

Cho

Nam

et al. 2015

Animal Cells and Systems

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Hyperglycemia-induced pancreatic β-cell apoptosis causes serious health complications in diabetic patients. Recently, studies demonstrated that silk and silk-related materials have anti-diabetic effects. We previously reported that silk fibroin hydrolysate (SFH) has anti-diabetic effects through increased pancreatic β-cell mass in type 2 diabetic animals (C 57 BL/KsJ db/db ). However, it is not known whether SFH has anti-apoptotic effects in hyperglycemic conditions. The present study investigates the anti-apoptotic effects of SFH on high glucoseinduced apoptosis using RIN5F cells, a rat pancreatic β-cell line. Hyperglycemic conditions decreased RIN5F cell viability in a concentration-dependent manner. High glucose treatment of 33 mM or higher caused a significant decrease in RIN5F cell viability. However, addition of SFH significantly recovered cell viability in the presence of high glucose. Flow cytometry analysis showed that high glucose treatment significantly increased early stage apoptosis in RIN5F cells. This was inhibited by SFH treatment, which significantly decreased not only early stage apoptosis but also decreased the production of nitrite. Additionally, SFH protected RIN5F cells from oxidative stress-induced apoptosis. These results suggest that SFH has anti-apoptotic effects by protecting pancreatic β-cell from high glucose and/or oxidative stress. Our results support in vivo anti-diabetic effects of SFH and validation of the traditional use of silkworm and silkworm materials in the treatment of diabetes.

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“…All the above-mentioned mechanisms lead to hyperglycemia, which is, by itself, a recognized stressor for β-cells, suppressing insulin secretion and/or leading to β-cell apoptosis in vitro [102][103][104] via oxidative stress [105]. Β-cell failure appears to play a major role in T2DM development [106,107] and is thus very likely to play a key role in NODAT development as well.…”

Section: Hyperglycemiamentioning

confidence: 99%

Prevalence of Metabolic Syndrome in Organ Transplantation: A Review of the Literature

Pinna¹,

Pagotto²

2015

Endocrinol Metab Syndr

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The clinical features of the Metabolic Syndrome (MS) as risk factors for transplantation have been cited separately and extensively in the transplant literature. There are few studies in literature evaluating the prevalence of MS before and after solid organ transplantation.MS puts transplant patients at risk in in two ways: 1) MS is one more risk factor to be considered in the pretransplantation workup; and 2) the combined risk of cardiovascular disease post-transplantation as a side effect of immunosuppressive medication together with the risk from cardiovascular disease stemming from the MS might put a post-transplantation patient at vastly increased risk for a cardiovascular event.There are several reports on the treatment of MS expecially after transplantation; from lifestyle changes to drug therapies. However, to now, guidelines about management of these patients are lacking.

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Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells

Cited by 47 publications

References 39 publications

Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells

Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells

Anti-apoptotic effects of silk fibroin hydrolysate in RIN5F cell on high glucose condition

Prevalence of Metabolic Syndrome in Organ Transplantation: A Review of the Literature

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