RESUMO
Diabetic nephropathy (DN) is one of the most common chronic complications of diabetes, which is associated with an increased oxidative stress induced by hyperglycemia and alterations in DJ-1/NF-E2-related factor-2 (Nrf2) pathway. In the present study, we investigated the role and the proper time nodes of DJ-1/Nrf2 pathway in the pathogenesis of DN. Diabetes mellitus (DM) model of rats was induced by intraperitoneal injection of streptozotocin (STZ) on male Sprague-Dawley (SD) rats. Then, the diabetic rats were divided into 4, 8 and 12 weeks groups. As early at 4 weeks of diabetes, renal histologic evaluation score, cystatin C (Cys C), ß2-microglobulin (ß2-MG) and malondialdehyde (MDA) levels were increased, and total antioxidative capacity (T-AOC) level was decreased as compared with that in the control group. The protein expressions of DJ-1, NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were upregulated compared with the control group from 4 weeks and further increased with the progression of DM. The protein expressions of DJ-1, Nrf2 and HO-1 in renal tissues have good line correlations with renal histologic evaluation score, respectively. Taken together, these results suggested that the activation of DJ-1/Nrf2 pathway was involved in the pathogenesis of diabetic nephropathy in rats.
Assuntos
Nefropatias Diabéticas/etiologia , Fator 2 Relacionado a NF-E2/fisiologia , Proteína Desglicase DJ-1/fisiologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
The objective of the present study was to investigate acute kidney injury (AKI) induced by myocardial ischemia/reperfusion (MIR) in diabetic rats and elucidate its underlying mechanism. A rat model of MIR was established by left anterior descending coronary artery occlusion for 30 min, followed by reperfusion for 2 h. Rats were randomly divided into four groups: i) Sham group, ii) sham + MIR group, iii) diabetic group and iv) diabetes + MIR group. Myocardial injury was detected by plasma creatine kinase isoenzyme MB and lactate dehydrogenase assays. AKI induced by MIR in diabetic rats was characterized by increases in cystatin C and ß2-microglobulin levels. Oxidative stress injury was accompanied by an increase of malondialdehyde levels and a decrease of total antioxidative capacity in the renal tissues. Immunohistochemistry and western blot analysis demonstrated that the expression of DJ-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased in the diabetes + MIR group compared with that in the sham + MIR and diabetic groups. Taken together, these results suggested that AKI induced by MIR in diabetic rats may be associated with activation of the DJ-1/Nrf2 pathway.
RESUMO
Patients with diabetes are more vulnerable to renal ischemia/reperfusion (I/R) injury, which is implicated in hyperglycemia-induced oxidative stress. We previously reported that the hyperglycemia-induced inhibition of DJ-1, a novel oncogene that exhibits potent antioxidant activity, is implicated in the severity of myocardial I/R injury. In the present study, we aimed to explore the role of DJ-1 in hypoxia/reoxygenation (H/R) injury in renal cells exposed to high glucose (HG). For this purpose, NRK-52E cells were exposed to HG (30 mM) for 48 h and then exposed to hypoxia for 4 h and reoxygenation for 2 h, which significantly decreased cell viability and superoxide dismutase (SOD) activity, and increased the malondialdehyde (MDA) content, accompanied by a decrease in DJ1 protein expression. The overexpression of DJ1 by transfection with a DJ1 overexpression plasmid exerted protective effects against HG-induced H/R injury, as evidenced by increased CCK-8 levels and SOD activity, the decreased release of lactate dehydrogenase (LDH) and the decreased MDA content, and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO1) expression. Similar effects were observed following treatment with the antioxidant, N-acetylcysteine. These results suggest that the overexpression of DJ1 reduces oxidative stress and attenuates H/R injury in NRK-52E cells exposed to HG.
Assuntos
Células Epiteliais/efeitos dos fármacos , Glucose/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Proteína Desglicase DJ-1/metabolismo , Animais , Antioxidantes/farmacologia , Western Blotting , Hipóxia Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cistina/análogos & derivados , Cistina/farmacologia , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Heme Oxigenase-1/metabolismo , Túbulos Renais Proximais/citologia , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oxigênio/farmacologia , Proteína Desglicase DJ-1/genética , Ratos , Superóxido Dismutase/metabolismo , Fatores de Tempo , TransfecçãoRESUMO
A new class of highly oxygenated Schisandra nortriterpenoids, lancolides A-D (1-4), from Schisandra lancifolia, represents the first example of natural products that possess a tricyclo[6.3.0.0(2,11)]undecane-bridged system. Their structures were elucidated by NMR spectra, X-ray diffraction, and quantum chemical calculations. Lancolides A (1) and D (4) had specific antiplatelet aggregation induced by platelet-activating factor (PAF).