scholarly journals Therapeutic Effect of MG132 on the Aortic Oxidative Damage and Inflammatory Response in OVE26 Type 1 Diabetic Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao Miao ◽  
Wenpeng Cui ◽  
Weixia Sun ◽  
Ying Xin ◽  
Bo Wang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Chronic Treatment ◽  
Low Dose ◽  
Matched Control ◽  
Related Factor ◽  
Nuclear Factor ◽  
Diabetic Mice ◽  
Pathological Changes ◽  
Nrf2 Expression

The present study tested whether MG132 increases vascular nuclear factor E2-related factor-2 (Nrf2) expression and transcription to provide a therapeutic effect on diabetes-induced pathogenic changes in the aorta. To this end, three-month-old OVE26 diabetic and age-matched control mice were intraperitoneally injected with MG-132, 10 μg/kg daily for 3 months. OVE26 transgenic type 1 diabetic mice develop hyperglycemia at 2-3 weeks of age and exhibit albuminuria at 3 months of age with mild increases in TNF-αexpression and 3-NT accumulation in the aorta. Diabetes-induced significant increases in the wall thickness and structural derangement of aorta were found in OVE26 mice with significant increases in aortic oxidative and nitrosative damage, inflammation, and remodeling at 6 months of diabetes, but not at 3 months of diabetes. However, these pathological changes seen at the 6 months of diabetes were abolished in OVE26 mice treated with MG-132 for 3 months that were also associated with a significant increase in Nrf2 expression in the aorta as well as transcription of downstream genes. These results suggest that chronic treatment with low-dose MG132 can afford an effective therapy for diabetes-induced pathogenic changes in the aorta, which is associated with the increased Nrf2 expression and transcription.

scholarly journals Nuclear Factor Erythroid 2-Related Factor 2 Deletion Impairs Glucose Tolerance and Exacerbates Hyperglycemia in Type 1 Diabetic Mice

2010 ◽  
Vol 333 (1) ◽  
pp. 140-151 ◽  
Author(s):  
Lauren M. Aleksunes ◽  
Scott A. Reisman ◽  
Ronnie L. Yeager ◽  
Michael J. Goedken ◽  
Curtis D. Klaassen
Keyword(s):  
Glucose Tolerance ◽  
Related Factor ◽  
Nuclear Factor ◽  
Diabetic Mice

scholarly journals CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1026
Author(s):  
Ji-Eun Kim ◽  
Hana Park ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
Signaling Pathways ◽  
Seizure Activity ◽  
Molecular Layer ◽  
Antioxidant Properties ◽  
Acid Methyl Ester ◽  
Related Factor ◽  
Nuclear Factor ◽  
Reactive Astrogliosis ◽  
Nrf2 Expression

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present study, we evaluated whether CDDO-Me affects astroglial responses to status epilepticus (SE, a prolonged seizure activity) in the rat hippocampus in order to understand the underlying mechanisms of reactive astrogliosis and astroglial apoptosis. Under physiological conditions, CDDO-Me increased Nrf2 expression in the hippocampus without altering activities (phosphorylations) of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphatidylinositol-3-kinase (PI3K), and AKT. CDDO-Me did not affect seizure activity in response to pilocarpine. However, CDDO-Me ameliorated reduced astroglial Nrf2 expression in the CA1 region and the molecular layer of the dentate gyrus (ML), and attenuated reactive astrogliosis and ML astroglial apoptosis following SE. In CA1 astrocytes, CDDO-Me inhibited the PI3K/AKT pathway by activating PTEN. In contrast, CDDO-ME resulted in extracellular signal-related kinases 1/2 (ERK1/2)-mediated Nrf2 upregulation in ML astrocytes. Furthermore, CDDO-Me decreased nuclear factor-κB (NFκB) phosphorylation in both CA1 and ML astrocytes. Therefore, our findings suggest that CDDO-Me may attenuate SE-induced reactive astrogliosis and astroglial apoptosis via regulation of ERK1/2-Nrf2, PTEN-PI3K-AKT, and NFκB signaling pathways.

scholarly journals Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao Xing ◽  
Chi Zhang ◽  
Minglong Shao ◽  
Qingyue Tong ◽  
Guirong Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Low Dose ◽  
X Rays ◽  
Diabetic Mice ◽  
Low Dose Radiation ◽  
Single Exposure ◽  
Akt Phosphorylation ◽  
And Function ◽  
Nrf2 Expression ◽  
Dose Radiation

Repetitive exposure of diabetic mice to low-dose radiation (LDR) at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days) and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above.

scholarly journals Optimal LDR to Protect the Kidney From Diabetes: Whole-Body Exposure to 25 mGy X-rays Weekly for 8 Weeks Efficiently Attenuates Renal Damage in Diabetic Mice

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878984 ◽  
Author(s):  
Jie Cheng ◽  
Fengsheng Li ◽  
Guanjun Wang ◽  
Weiying Guo ◽  
Shan Huang ◽  
...  
Keyword(s):  
Low Dose ◽  
Collagen Iv ◽  
Whole Body ◽  
Detectable Effect ◽  
X Rays ◽  
Diabetic Mice ◽  
Low Dose Radiation ◽  
Functional Changes ◽  
Renal Expression

To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect the kidney from diabetes, type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age-matched normal mice received whole-body exposure to 12.5 or 25 mGy either every other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All these renal pathological and functional changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens. However, whole-body exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8 weeks provided a better prevention of diabetic nephropathy than other LDR regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no detectable effect on the kidney of normal mice, but whole-body exposure to normal mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and renal expression of collagen IV and fibronectin. These results suggest that whole-body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect the kidney from diabetes.

scholarly journals CDDO-Me Attenuates Vasogenic Edema and Astroglial Death by Regulating NF-κB p65 Phosphorylations and Nrf2 Expression Following Status Epilepticus

2019 ◽  
Vol 20 (19) ◽  
pp. 4862 ◽  
Author(s):  
Min-Ju Kim ◽  
Hana Park ◽  
Seo-Hyeon Choi ◽  
Min-Jeong Kong ◽  
Ji-Eun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Status Epilepticus ◽  
Vasogenic Edema ◽  
Acid Methyl Ester ◽  
Nuclear Factor Κb ◽  
Related Factor ◽  
Nuclear Factor ◽  
Edema Formation ◽  
Tnf Α ◽  
Nrf2 Expression

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that has anti-inflammatory, antioxidant, and neuroprotective activities. In the present study, we evaluate the effects of CDDO-Me on serum extravasation and astroglial death in the rat piriform cortex (PC) induced by status epilepticus (a prolonged seizure activity, SE) in order to propose an underlying pharmacological mechanism of CDDO-Me and its availability for treatment of vasogenic edema. CDDO-Me effectively mitigated serum extravasation and a massive astroglial loss in the PC following SE. CDDO-Me abrogated tumor necrosis factor-α (TNF-α) synthesis in activated microglia by inhibiting nuclear factor-κB (NF-κB) p65 serine 276 phosphorylation. CDDO-Me also abolished NF-κB threonine 435 phosphorylation in endothelial cells and TNF-α-mediated-phosphatidylinositol-3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling cascades, which trigger vasogenic edema following SE. Furthermore, CDDO-Me increased astroglial viability via the up-regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. Therefore, our findings suggest that CDDO-Me may ameliorate SE-induced vasogenic edema formation by regulating NF-κB p65 phosphorylations in microglia as well as endothelial cells and enhancing Nrf2 expression in astrocytes, respectively.

scholarly journals Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2 (Nrf2) expression in gastric cancer

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Yota Kawasaki ◽  
Sumiya Ishigami ◽  
Takaaki Arigami ◽  
Yoshikazu Uenosono ◽  
Shigehiro Yanagita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Related Factor ◽  
Nuclear Factor ◽  
Clinicopathological Significance ◽  
Nrf2 Expression

scholarly journals Hepatic functional and pathological changes of type 1 diabetic mice in growing and maturation time

2019 ◽  
Vol 23 (8) ◽  
pp. 5794-5807 ◽  
Author(s):  
Saizhi Jiang ◽  
Xiaoqiang Tang ◽  
Kai Wang ◽  
Yaqing Liang ◽  
Yan Qian ◽  
...  
Keyword(s):  
Diabetic Mice ◽  
Pathological Changes ◽  
Maturation Time

Attenuation of diabetes-induced renal dysfunction by multiple exposures to low-dose radiation is associated with the suppression of systemic and renal inflammation

2009 ◽  
Vol 297 (6) ◽  
pp. E1366-E1377 ◽  
Author(s):  
Chi Zhang ◽  
Yi Tan ◽  
Weiying Guo ◽  
Cai Li ◽  
Shunzi Ji ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Renal Dysfunction ◽  
Western Blotting ◽  
Low Dose ◽  
Diabetic Mice ◽  
Pathological Changes ◽  
Low Dose Radiation ◽  
Renal Inflammation ◽  
Multiple Exposures ◽  
Dose Radiation

Renal protection against diabetes-induced pathogenic injuries by multiple exposures to low-dose radiation (LDR) was investigated to develop a novel approach to the prevention of renal disease for diabetic subjects. C57BL/6J mice were given multiple low-dose streptozotocin (STZ; 60 × 6 mg/kg) to produce a type 1 diabetes. Two weeks after diabetes onset, some of diabetic mice and age-matched nondiabetic mice were exposed whole body to 25 mGy X-rays every other day for 2, 4, 8, 12, and 16 wk. Diabetes caused a significant renal dysfunction, shown by time-dependent increase in urinary microalbumin (Malb) and decrease in urinary creatinine (Cre), and pathological changes, shown by significant increases in renal structural changes and PAS-positive staining. However, diabetes-induced renal dysfunction and pathological changes were significantly, albeit partially, attenuated by multiple exposures to LDR. Furthermore, LDR protection against diabetes-induced renal dysfunction and pathological changes was associated with a significant suppression of diabetes-increased systemic and renal inflammation, shown by significant increases in serum and renal TNFα, ICAM-1, IL-18, MCP-1, and PAI-1 contents. To further explore the mechanism by which LDR prevents diabetes-induced renal pathological changes, renal oxidative damage was examined by Western blotting and immunohistochemical staining for 3-nitrotyrosine and 4-hydroxynonenal. Significant increase in oxidative damage was observed in diabetic mice, but not diabetic mice, with LDR. Renal fibrosis, examined by Western blotting of connective tissue growth factor and Masson's trichrome staining, was also evident in the kidneys of diabetic mice but not diabetic mice with LDR. These results suggest that multiple exposures to LDR significantly suppress diabetes-induced systemic and renal inflammatory response and renal oxidative damage, resulting in a prevention of the renal dysfunction and fibrosis.

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