Insulinoma cells in culture show pronounced sensitivity to alloxan-induced oxidative stress

Zhang, H.; �llinger, K.; Brunk, U.

doi:10.1007/s001250050330

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…In agreement with others, Alloxan intake was associated with generation of reactive oxygen species (i.e., increased malondialdehyde and decrease Glutathione levels) (Zhang et al, 1995;Beisswenger et al, 2005;Hakim and Pflueger, 2010;Bandeira Sde et al, 2012;Rahigude et al, 2012;Shodehinde and Oboh, 2013). Oxidative stress induces renal damage through several mechanisms.…”

Section: Increased Tissue Levels Of Lipid Peroxide and Decreased Glutsupporting

confidence: 86%

Renal damage following Alloxan‐induced diabetes is associated with generation of reactive oxygen species, alterations of p53, TGF‐β1, and extracellular matrix metalloproteinases in rats

Aziz

Badary

Hussein

2017

Cell Biology International

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Renal damage is a common problem in diabetes. Alloxan, a potent hyperglycemic and diabetogenic molecule, can induce diabetes through oxidative stress-related mechanisms. Here, we hypothesize that "Alloxan-induced renal damage is associated with alterations of p53, TGF-β1, and extracellular matrix metalloproteinases." To test our hypothesis, we established an animal model (male abino rats) and induced diabetes by intraperitoneal injection of Alloxan monohydrate. Rats with fasting blood glucose level ≥ 200 mg/dL were considered diabetic and were sacrificed after 14, 28, and 42 day intervals. Tissue levels of malondialdehyde and glutathione levels (markers of oxidative stress), and serum MMP-1 were measured. The expression patterns of p53, TGF-β1were evaluated using Western blot and immunohistochemical methods. TIMP-1 expression pattern was determined using RT-PCR and immunohistochemical methods. Alloxan treatment induced histological features of renal damage (inflammation and fibrosis) and was associated with deterioration of the renal functions (elevated blood urea nitrogen and creatinin levels), hyperglycemia, and oxidative stresss (increased malondialdehyde and decreased glutathione levels). There was over-expression of the TGF-β1 protein (profibrogenic protein), p53 (proapoptotic protein), and alterations of extracellular matrix proteins (low level of serum MMP-1 and over-expression of TIMP-1). Alterations of TGF-β, p53, and extracellular matrix metalloproteinases contribute to the pathogenesis of Alloxan-induced renal damage.

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Section: Increased Tissue Levels Of Lipid Peroxide and Decreased Glutsupporting

confidence: 86%

Renal damage following Alloxan‐induced diabetes is associated with generation of reactive oxygen species, alterations of p53, TGF‐β1, and extracellular matrix metalloproteinases in rats

Aziz

Badary

Hussein

2017

Cell Biology International

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“…In previous studies on HIT, RIN, and several other types of cells, we have shown that oxidative stress induces cell degeneration due to lysosomal labilization and leakage of damaging lysosomal contents into the cytosol. Since lysosomal labilization, as well as cellular degeneration and death, could be largely prevented by initially allowing the cells to endocytose the potent iron-chelator desferrioxamine, and transport it to their acidic vacuolar apparatus, the effects seem to be dependent on the intralysoso-ma1 presence of iron in low-molecular-weight, redox-active form (6,47,49,52).…”

Section: Discussionmentioning

confidence: 99%

A short exposure to a high‐glucose milieu stabilizes the acidic vacuolar apparatus of insulinoma cells in culture to ensuing oxidative stress

Olejnicka

Öllinger

Brunk

1997

APMIS

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U. T. A short exposure to a high-glucose milieu stabilizes the acidic vacuolar apparatus of insulinoma cells in culture to ensuing oxidative stress. APMIS 105:It was recently suggested that extracellular hydrogen peroxide, after diffusing into and throughout adjacent cellswhich may be the case if they have only a weak capacity to degrade hydrogen peroxidelabilizes their lysosomal compartment due to its content of low-molecular-weight iron in redox-active form. The iron would be present as a consequence of normal autophagocytotic degradation of various iron-containing metalloproteins. Beta-and insulinoma cells are especially vulnerable to oxidative stress, since they possess only low capacity to degrade hydrogen peroxide, and, perhaps, since they normally have a certain degree of autophagocytotic degradation of secretory granules with some iron contentcrinophagy. The toxicity to beta cells of oxidative stress, such as an exposure to alloxan, that results in extracellular formation of hydrogen peroxide, is considerably reduced if animals are initially given an intravenous bolus dose of glucose, temporarily bringing up the blood level to about 20 mM. In this study it was demonstrated that already as short an exposure as 30 min to 20 mM D-glucose reduces the sensitivity of HIT and NIT insulinoma cells in culture to a subsequent exposure to hydrogen peroxide. In parallel, exposure to such a high-glucose medium also reduces their desferrioxamine-available amount of iron and, moreover, stabilizes their lysosomal membranes against oxidative stressthus preventing diffusion to the cytosol of damaging lysosomal contents following iron-catalyzed, Fenton-type, intralysosomal reactions. We suggest that both general autophagocytotic turnover and, in particular, crinophagy of secretory granules are decreased by an increased glucose concentration of the surrounding milieu, with attendant reduced amounts of intralysosomal lowmolecular-weight iron and, thus, diminished sensitivity to oxidative stress.

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Diverse Effects of Hydrogen Peroxide on Cytosolic Ca2+ Homeostasis in Rat Pancreatic .BETA.-cells.

Nakazaki

Kakei

Yaekura

et al. 2000

Cell Struct. Funct.

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ABSTRACT. Oxygen-free radicals are thought to be a major cause of b-cell dysfunction in diabetic animals induced by alloxan or streptozotocin. We evaluated the effect of H2O2 on cytosolic Ca 2+ concentration ([Ca 2+ ]i) and the activity of ATP-sensitive potassium (K + ATP) channels in isolated rat pancreatic b-cells using microfluorometry and patch clamp techniques. Exposure to 0.1 mM H2O2 in the presence of 2.8 mM glucose increased [Ca 2+ ]i from 114.3±15.4 nM to 531.1±71.9 nM (n=6) and also increased frequency of K + ATP channel openings. The intensity of NAD(P)H autofluorescence was conversely reduced, suggesting that H2O2 inhibited the cellular metabolism. These three types of cellular parameters were reversed to the control level on washout of H2O2, followed by a transient increase in [Ca 2+ ]i, the transient inhibition of K + ATP channels associated with action currents and increase of the NAD(P)H intensity with an overshoot. In the absence of external Ca 2+ , 0.1 mM H2O2 increased [Ca 2+ ]i from 88.8±7.2 nM to 134.6±8.3 nM. Magnitude of [Ca 2+ ]i increase induced by 0.1 mM H2O2 was decreased after treatment of cells with 0.5 mM thapsigargin, an inhibitor of endoplasmic reticulum Ca 2+ pump (45.8±4.9 nM vs 15.0±4.8 nM). Small increase in [Ca 2+ ]i in response to an increase of external Ca 2+ from zero to 2 mM was further facilitated by 0.1 mM H2O2 (330.5±122.7 nM). We concluded that H2O2 not only activates K + ATP channels in association with metabolic inhibition, but also increases partly the Ca 2+ permeability of the thapsigargin-sensitive intracellular stores and of the plasma membrane in pancreatic b-cells.

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Insulinoma cells in culture show pronounced sensitivity to alloxan-induced oxidative stress

Cited by 3 publications

References 19 publications

Renal damage following Alloxan‐induced diabetes is associated with generation of reactive oxygen species, alterations of p53, TGF‐β1, and extracellular matrix metalloproteinases in rats

Renal damage following Alloxan‐induced diabetes is associated with generation of reactive oxygen species, alterations of p53, TGF‐β1, and extracellular matrix metalloproteinases in rats

A short exposure to a high‐glucose milieu stabilizes the acidic vacuolar apparatus of insulinoma cells in culture to ensuing oxidative stress

Diverse Effects of Hydrogen Peroxide on Cytosolic Ca2+ Homeostasis in Rat Pancreatic .BETA.-cells.

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