Jun dimerization protein 2 is a critical component of the Nrf2/MafK complex regulating the response to ROS homeostasis.

Oxidative stress and reactive oxygen species (ROS) are associated with diseases such as cancer, cardiovascular complications, inflammation and neurodegeneration. Cellular defense systems must work constantly to control ROS levels and to prevent their accumulation. We report here that the Jun dimerization protein 2 (JDP2) has a critical role as a cofactor for transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and small Maf protein family K (MafK) in the regulation of the antioxidant-responsive element (ARE) and production of ROS. Chromatin immunoprecipitation-quantitative PCR (qPCR), electrophoresis mobility shift and ARE-driven reporter assays were carried out to examine the role of JDP2 in ROS production. JDP2 bound directly to the ARE core sequence, associated with Nrf2 and MafK (Nrf2-MafK) via basic leucine zipper domains, and increased DNA-binding activity of the Nrf2-MafK complex to the ARE and the transcription of ARE-dependent genes. In mouse embryonic fibroblasts from Jdp2-knockout (Jdp2 KO) mice, the coordinate transcriptional activation of several ARE-containing genes and the ability of Nrf2 to activate expression of target genes were impaired. Moreover, intracellular accumulation of ROS and increased thickness of the epidermis were detected in Jdp2 KO mice in response to oxidative stress-inducing reagents. These data suggest that JDP2 is required to protect against intracellular oxidation, ROS activation and DNA oxidation. qPCR demonstrated that several Nrf2 target genes such as heme oxygenase-1, glutamate-cysteine ligase catalytic and modifier subunits, the notch receptor ligand jagged 1 and NAD(P)H dehydrogenase quinone 1 are also dependent on JDP2 for full expression. Taken together, these results suggest that JDP2 is an integral component of the Nrf2-MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE.

Fisetin induces transcription of NADPH:quinone oxidoreductase gene through an antioxidant responsive element-involved activation.

Induction of phase II enzymes such as NADPH:quinone oxidoreductase (QR) can reduce carcinogen-induced mutagenesis and tumor formation. In our search for novel dietary anticarcinogens, fisetin, a flavonol widely distributed in fruits and vegetables was found to induce QR activity in murine hepatoma 1c1c7 cells. The cells were treated with various concentrations of fisetin, and then were assessed for cell growth, QR activity, QR mRNA expression and transcription activation of the QR gene. The results showed that fisetin induced QR activity in time- and dose-dependent manner in the concentration range of 0.1 to 10 microM, and the activity induction was associated with QR mRNA expression as detected by reverse transcription-PCR. Furthermore, transfection studies using a human QR antioxidant/electrophile-response element (ARE/EpRE) reporter construct demonstrated that fisetin activated the ARE/EpRE. These results show that fisetin increases QR activity by transcriptional activation of the ARE/EpRE, suggesting a novel mechanism by which dietary fisetin may be implicated in cancer chemoprevention.

Expanded cavum septi pellucidi and cavum vergae associated with behavioral symptoms relieved by a stereotactic procedure: case report.

CASE REPORT: A 6-year-old boy had symptoms such as unstable gait, behavioral symptoms, and irregular appetite, evacuation, and sleep. Giant cavum septi pellucidi and cavum vergae of 3 x 3 x 5 cm were revealed by computed tomography (CT) and magnetic resonance imaging (MRI). After stereotactic cyst-peritoneal shunting, regression of the cavities was revealed by CT and MRI, in association with marked improvement in the above-described symptoms. In the corpus callosum particularly, which had been preoperatively revealed on sagittal MRI sections to be extended circumferentially as a result of compression by a cyst; the compression was relieved postoperatively, and compression of the pericallosal brain tissue was also relieved. CONCLUSIONS: Compression of the brain tissue around the cyst (limbic system, etc.) was considered the most important cause of the behavioral symptoms in this patient.

[Prediction of avascular necrosis in the femoral head following fracture dislocation--using the electrochemically generated hydrogen clearance method].

In order to predict necrosis of the femoral head following fracture-dislocation, the blood flow in the femoral heads in twenty-five hips was measured immediately after reduction and three, six, nine and twelve months thereafter. Twenty hips were followed up for more than one year (average 26.3 months) radiographically. Seven out of twenty hips had very low blood flow in the weight bearing areas three months after reduction. Five of seven had very low blood flow six and nine months after reduction and resulted in necrosis which was determined radiographically. The other two of seven recovered the blood flow and have not resulted in necrosis. Thirteen hips with normal blood flow three months after reduction also did not undergo necrosis. It is possible to predict the incidence of necrosis after fracture-dislocation by measuring the blood flow of the femoral head with the electrochemically generated hydrogen clearance method.