Impaired Redox Signaling and Antioxidant Gene Expression in Endothelial Cells in Diabetes: A Role for Mitochondria and the Nuclear Factor-E2-Related Factor 2-Kelch-Like ECH-Associated Protein 1 Defense Pathway

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.

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Multiwall Carbon Nanotube-Induced Apoptosis and Antioxidant Gene Expression in the Gills, Liver, and Intestine ofOryzias latipes

BioMed Research International ◽

10.1155/2015/485343 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Jin Wuk Lee ◽

Young Chul Choi ◽

Rosa Kim ◽

Sung Kyu Lee

Keyword(s):

Gene Expression ◽

Multiwall Carbon Nanotubes ◽

Gene Induction ◽

Multiwall Carbon Nanotube ◽

Antioxidant Gene ◽

Significant Gene ◽

Antioxidant Gene Expression ◽

And Gender ◽

Induced Apoptosis ◽

Multiwall Carbon

Multiwall carbon nanotubes (MWCNTs) have many attractive properties with potential applications in various fields. Despite their usefulness, however, the associated waste can be hazardous to the environment. To examine adverse effects in aquatic environments,Oryzias latipeswere exposed to MWCNTs dispersed in water for 14 days and apoptosis and antioxidant gene expression were observed. This work showed that in gills exposed to 100 mg/L MWCNTs for 4 days, there was significantp53,caspase-3 (Cas3),caspase-8 (Cas8), andcaspase-9 (Cas9)gene expression relative to the controls, whilecatalase (CAT)andglutathione-S-transferase (GST)expression were reduced. At 14 days,CAT,GST, andmetallothionein (MT)were induced significantly in the gills andCas3,Cas8, andCas9were induced in the liver. No significant gene induction was seen in intestine. Intracellular reactive oxygen species (ROS) were increased significantly only at 14 days. Histologically, no apoptosis was observed with exposure to 100 mg/L MWCNTs for 21 days. The gills were more sensitive to MWCNT toxicity than the other organs. Males had higher apoptosis gene induction than females. These results demonstrated that MWCNTs could cause apoptosis in a manner influenced by tissue and gender in aqueous environments.

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