Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation

Bernotti, Sandra; Seidman, Ernest G.; Sinnett, Daniel; Brunet, Sylvain; Dionne, Serge; Delvin, Edgard; Lévy, Émile

doi:10.1152/ajpgi.00042.2003

Cited by 51 publications

(43 citation statements)

References 55 publications

(57 reference statements)

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“…Cholesterol is a determinant of membrane fluidity and plays a role in the function of membrane proteins. It is reasonable and consistent with published data to hypothesize that ferrous ion induced radical generation leads to membrane disturbances and in a compensatory response the cells may attempt to increase the cholesterol synthetic capacity [34][35][36]. In reports published so far the Fe(II)-dependent effects on cholesterol metabolism vary depending on the experimental system used.…”

Section: Discussionsupporting

confidence: 87%

Control of smooth muscle cell proliferation by ferrous iron

et al. 2006

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Section: Discussionsupporting

confidence: 87%

Control of smooth muscle cell proliferation by ferrous iron

et al. 2006

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“…The loss of GSH through the membrane may in turn depend on membrane oxidative alterations due to the diabetes-induced oxidative stress; lipid peroxidation has actually been described to be increased in diabetic rat liver (11,58,59), and peroxidized membrane can exhibit altered permeability (60,61) and transport functions (62,63). Therefore, our data confirm the existence of GSH decrease and increased oxidative stress in diabetes.…”

Section: Discussionsupporting

confidence: 79%

Impaired synthesis contributes to diabetes-induced decrease in liver glutathione

et al. 2012

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Abstract. Diabetes-induced glutathione (GSH) decrease is usually ascribed to GSH oxidation. Here we investigate, in streptozotocin-treated rats, if impairment of GSH synthesis contributes to GSH decrease in diabetic liver, and if antioxidant treatments can provide protection. Diabetic rats were divided into 3 groups: untreated diabetic rats (UD); N-acetylcysteine (NAC)-treated diabetic rats; taurine (TAU)-treated diabetic rats; a group of non-streptozotocin-treated rats was used as control (CTR). All rats were sacrificed at 40 weeks of age. Diabetes induced hepatic glutathione decrease, but oxidized glutathione (GSSG) did not increase significantly. Accumulations of cysteine and cysteinyl-glycine in UD suggest respectively decreased glutathione synthesis and increased loss through the plasma membrane with subsequent degradation. Decreased expression of γ-glutamyl-cysteine synthetase in UD is consistent with repressed GSH synthesis. Moreover, diabetes caused increase of GSSG/GSH ratio and induction of heme oxygenase-1, both signs of oxidative stress. Supplementation with NAC or TAU resulted in amelioration of glutathione levels, probably depending on antioxidant activity, more efficient glutathione synthesis and decreased GSH loss and degradation. In conclusion, impaired synthesis and increased loss and degradation of GSH appear to contribute to a decrease in GSH levels in diabetic liver. NAC and TAU are able to partially protect from oxidative stress and GSH decrease, while enhancing GSH synthesis and restricting GSH loss. IntroductionOxidative stress is widely considered as one of the main mechanisms involved in the pathogenesis of chronic complications of diabetes, although its role is under constant discussion (1-6). Several studies have underlined the participation of oxidative mechanisms in the generation of some advanced glycation end-products (AGE) (7), which are considered responsible for protein alterations leading to diabetic sequelae (8). Moreover, signs of increased oxidative stress in diabetes have been recognized in the plasma (9,10) and inside the cells (10,11); however, studies on the content of antioxidant enzymes have yielded contrasting results (12-15), probably owing to differences in diabetes models, diabetes duration and the organs evaluated.Glutathione (GSH) is the main cellular thiol participating in cellular redox reactions, and the liver is the main site of GSH synthesis (16). Several studies have shown that GSH content is decreased in various tissues of diabetic organisms (13,14,17,18); this could be the cause and consequence of increased oxidative stress. Decrease in glutathione levels has been frequently reported in diabetes, and could occur through decreased synthesis, increased utilization (consumption or degradation) or a combination of both (19).Synthesis of GSH depends essentially on two enzymes acting sequentially [γ-glutamyl-cysteine synthetase (gGCS), EC 6.3.2.2, and glutathione synthetase (GS), EC 6.3.2.3], but only the first is believed to be rate-determinant; availability ...

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“…ROS-mediated damage to cellular components is thought to contribute to the pathophysiology of numerous diseases that affect tissues of various organ systems, including the gastrointestinal (GI) tract (4,41). In addition, many types of mammalian cells rapidly produce ROS in response to various stimuli, leading to the hypothesis that ROS constitute biologically important signaling molecules.…”

mentioning

confidence: 99%

“…Cells exposed to ROS at high concentrations or for extended periods undergo cellular DNA damage, which is widely known to induce cell death via apoptosis and/or necrosis (11). Oxidative stress is known to contribute to various inflammatory conditions of the GI tract (4,41). In particular, ROS have been implicated in the pathogenesis of necrotizing enterocolitis (NEC), a devastating disease in premature infants that can lead to sepsis and death.…”

mentioning

confidence: 99%

Protein kinase D protects against oxidative stress-induced intestinal epithelial cell injury via Rho/ROK/PKC-δ pathway activation

Song¹,

Li²,

Lulla³

et al. 2006

American Journal of Physiology-Cell Physiology

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tein kinase D (PKD) is a novel protein serine kinase that has recently been implicated in diverse cellular functions, including apoptosis and cell proliferation. The purpose of our present study was 1) to define the activation of PKD in intestinal epithelial cells treated with H2O2, an agent that induces oxidative stress, and 2) to delineate the upstream signaling mechanisms mediating the activation of PKD. We found that the activation of PKD is induced by H2O2 in both a dose-and time-dependent fashion. PKD phosphorylation was attenuated by rottlerin, a selective PKC-␦ inhibitor, and by small interfering RNA (siRNA) directed against PKC-␦, suggesting the regulation of PKD activity by upstream PKC-␦. Activation of PKD was also blocked by a Rho kinase (ROK)-specific inhibitor, Y-27632, as well as by C3, a Rho protein inhibitor, demonstrating that the Rho/ROK pathway also mediates PKD activity in intestinal cells. In addition, H2O2-induced PKC-␦ phosphorylation was inhibited by C3 treatment, further suggesting that PKC-␦ is downstream of Rho/ROK. Interestingly, H 2O2-induced intestinal cell apoptosis was enhanced by PKD siRNA. Together, these results clearly demonstrate that oxidative stress induces PKD activation in intestinal epithelial cells and that this activation is regulated by upstream PKC-␦ and Rho/ROK pathways. Importantly, our findings suggest that PKD activation protects intestinal epithelial cells from oxidative stress-induced apoptosis. These findings have potential clinical implications for intestinal injury associated with oxidative stress (e.g., necrotizing enterocolitis in infants). Rho kinase; protein kinase C-␦

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Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation

Cited by 51 publications

References 55 publications

Control of smooth muscle cell proliferation by ferrous iron

Control of smooth muscle cell proliferation by ferrous iron

Impaired synthesis contributes to diabetes-induced decrease in liver glutathione

Protein kinase D protects against oxidative stress-induced intestinal epithelial cell injury via Rho/ROK/PKC-δ pathway activation

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