Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus

Sechi, Leonardo A.; Ceriello, Antonio; Griffin, Chandi; Catena, Cristiana; Amstad, Paul; Schambelan, Morris; Bartoli, Ettore

doi:10.1007/s001250050638

Cited by 76 publications

(50 citation statements)

References 47 publications

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“…In response to oxidative stress, antioxidant enzymes are induced to protect cellular and tissue injury (18,19,27). Although Cu/Zn SOD and catalase mRNA levels have been shown to be significantly induced in the total kidney of untreated diabetic rats (18), we were not able to find any change in mRNA content of Cu/Zn SOD, GPX, and catalase in glomeruli of diabetic rats (19).…”

Section: Discussionmentioning

confidence: 56%

“…Indeed, involvement of oxidative stress has been indicated by the presence of lipid peroxidation products and 8-hydroxydeoxyguanosine in the kidney from streptozotocin (STZ)-induced diabetic rats (16,17). Regarding the defense system to oxidative stress, antioxidant enzymes such as catalase and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) were found to be enhanced in kidneys of STZ-induced diabetic rats (18). However, it remains unknown whether these findings reflect a common consequence of the tissue damage in diabetic kidney or oxidative stress has a primary role in the pathogenesis of diabetic kidney disease.…”

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confidence: 99%

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Effects of Antioxidants in Diabetes-Induced Oxidative Stress in the Glomeruli of Diabetic Rats

Koya

Hayashi

Kitada

et al. 2003

Journal of the American Society of Nephrology

253

175

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Abstract. Numerous reports have demonstrated that oxidative stress induced by diabetes plays an important role in the development and progression of diabetic vascular complications including nephropathy. Indeed, there is emerging evidence that the formation of reactive oxygen species (ROS) is a direct consequence of hyperglycemia. Biomarkers for oxidative damage to DNA, lipids, and proteins are also supporting the concept of increased oxidative stress in diabetes and diabetic nephropathy. However, there is an unanswered question: When does oxidative stress as a pathogenetic event occur in the process of diabetic nephropathy? To answer this question, glomerular ROS was imaged with the use of 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The image of DCF fluorescence was strong in glomeruli from diabetic rats as compared with that of glomeruli from nondiabetic control rats. mRNA expression of antioxidant enzymes such as catalase, glutathione peroxidase, Cu/Zn superoxide dismutase, and heme oxygenase-1 (HO-1) was also determined because oxidative stress definitely refers to the situation of an imbalance between the production of ROS and antioxidant defense. The mRNA expression of catalase, glutathione peroxidase, and Cu/Zn superoxide dismutase 2 wk after the induction of diabetes was not significantly different from that in control rats. Alternatively, mRNA and protein expression of HO-1 was strongly induced by 16-fold in diabetic glomeruli after the induction of diabetes. Antioxidant treatment with either vitamin E or probucol almost completely normalized HO-1 overexpression in diabetic glomeruli, supporting the existence of oxidative stress in the glomeruli of early diabetes. Furthermore, It has reported that antioxidant treatment with vitamin E, probucol, ␣-lipoic acid, or taurine normalized diabetes-induced not only renal dysfunction such as albuminuria and glomerular hypertension but also glomerular pathologies. In summary, oxidative stress by diabetes could play a crucial role in the development and progression of diabetic nephropathy, and antioxidant treatment could be a potential therapeutic procedure for diabetic nephropathy.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

Effects of Antioxidants in Diabetes-Induced Oxidative Stress in the Glomeruli of Diabetic Rats

Koya

Hayashi

Kitada

et al. 2003

Journal of the American Society of Nephrology

253

175

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“…5 mmol/l = 1.0, (n = 5 independent experiments for fibronectin and collagen IV, n = 3 for collagen I and III) tured in high glucose concentrations [35]. Increases in CuZnSOD mRNA concentrations have also been reported in endothelial cells under similar conditions [35] and in diabetic rat kidneys [36]. These results show, for the first time, the ability of the VSMC to respond to glucose-induced oxidative stress by increasing the mRNA levels of the SOD enzymes (both CuZnSOD and MnSOD).…”

Section: Discussionmentioning

confidence: 80%

The effects of glucose-induced oxidative stress on growth and extracellular matrix gene expression of vascular smooth muscle cells

et al. 1998

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Diabetes mellitus is a major risk factor for atherosclerosis. In population based studies diabetes is associated with an increased incidence of coronary heart disease [1], cerebrovascular disease and peripheral vascular disease [2]. The high prevalence of macrovascular disease is partly explained by the increased frequency of conventional risk factors and partly by risk factors specific for diabetes including hyperglycaemia, hyperinsulinaemia and dyslipidaemia. The view that diabetic vasculopathy is, at least in part, related to excess free radicals is supported by evidence such as increased lipid peroxidation [3] and reduced antioxidant reserve in patients with diabetes [4] and from studies showing a direct cytotoxic effect of free Diabetologia (1998) Summary Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy and this may include abnormalities in growth characteristics and the extracellular matrix. As the actual mechanisms by which glucose induces VSMC dysfunction remain unclear, the aim of this study was to assess the potential role of glucose-induced oxidative stress. Porcine aortic VSMCs were cultured for 10 days in either 5 mmol/l normal glucose or 25 mmol/l D-glucose (high glucose). There was evidence of oxidative stress as indicated by a 50 % increase in intracellular malondialdehyde (p < 0.05), increased mRNA expression of CuZn superoxide dismutase and Mn superoxide dismutase (by 51 % and 37 % respectively, p < 0.01) and a 50 % decrease in glutathione in 25 mmol/l D-glucose (p < 0.001). Growth was increased by 25.0 % (p < 0.01). mRNA expression of extracellular matrix proteins (collagens I, III, IV and fibronectin) was not altered by high glucose in these experimental conditions. Repletion of glutathione with N-acetyl L-cysteine (1 mmol/l) in VSMC grown in high glucose was associated with reduction in malondialdehyde and restored growth to that of normal glucose. The water soluble analogue of vitamin E, Trolox (200 mmol/l), reduced malondialdehyde concentrations, but had no effect on glutathione depletion or the increased growth rate seen with high glucose. The addition of buthionine sulphoximine (10 mmol/l) to VSMC cultured in normal glucose reduced glutathione, increased malondialdehyde and increased growth to a similar extent as that found in high glucose alone. These results suggest that thiol status, rather than lipid peroxides, is a key factor in modulating VSMC growth and that mRNA expression of extracellular matrix proteins is not increased in VSMC under conditions of glucose-induced oxidative stress. [Diabetologia (1998

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“…In contrast to the findings with SOD, neither high continuous glucose nor intermittent high glucose resulted in substantial induction of GPx or CAT activity in the retinal cells. Although we and others have shown that high glucose has been shown to induce GPx and CAT in many different cells and tissues [11,12,[32][33][34][35] , there is most certainly a divergent and perhaps cell-specific regulation of these antioxidant enzymes. Our lack of induction with GPx and CAT also fit well with similar findings in the retina of hyperglycemic animals [30] .…”

Section: Discussionmentioning

confidence: 80%

Attenuated Superoxide Dismutase Induction in Retinal Cells in Response to Intermittent High Versus Continuous High Glucose

Ihnat¹,

Kaltreider²,

Thorpe³

et al. 2007

American J. of Biochemistry and Biotechnology

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High glucose, particularly in oscillating conditions, produces an increase in oxidative stress and has been shown to result in an increase in diabetic complications, retinopathy in particular. The hypothesis of this work was that chronic exposure to intermittent high glucose results in an attenuated induction of an antioxidant response as compared to continuous high glucose exposure in isolated retinal cells In this work, human retinal pericytes and ARPE-19 cells were exposed to 5 mM or 30 mM continuous high glucose or to 5 mM oscillating daily with 30 mM glucose for 14 days. Levels of antioxidant proteins and activity and levels of reactive species protein adducts were measured. We demonstrate that the induction of total cellular superoxide dismutase (SOD) activity in isolated retinal pericytes and ARPE-19 cells is significantly attenuated in response to oscillating glucose as compared to continuous high glucose. We also show that a marker of nitrosative stress, 3-nitrotyrosine and a general marker of oxidized proteins, OxyBlot™, were significantly increased in both cell types exposed to intermittent high glucose as compared to continuous high glucose. Finally, we show that levels of nitrated MnSOD were increased in response to intermittent high versus continuous high glucose and that the addition of a reactive nitrogen species scavenger to oscillating glucose resulted in significantly increased levels of SOD activity. In conclusion, our results demonstrate for the first time a link between intermittent high glucose and a decreased induction of an antioxidant response of SOD.

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Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus

Cited by 76 publications

References 47 publications

Effects of Antioxidants in Diabetes-Induced Oxidative Stress in the Glomeruli of Diabetic Rats

Effects of Antioxidants in Diabetes-Induced Oxidative Stress in the Glomeruli of Diabetic Rats

The effects of glucose-induced oxidative stress on growth and extracellular matrix gene expression of vascular smooth muscle cells

Attenuated Superoxide Dismutase Induction in Retinal Cells in Response to Intermittent High Versus Continuous High Glucose

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