bTranscription factor Nrf2 is considered a master regulator of antioxidant defense in mammals. However, it is unclear whether this concept is applicable to nonmammalian vertebrates, because no animal model other than Nrf2 knockout mice has been generated to examine the effects of Nrf2 deficiency. Here, we characterized a recessive loss-of-function mutant of Nrf2 (nrf2 fh318 ) in a lower vertebrate, the zebrafish (Danio rerio). In keeping with the findings in the mouse model, nrf2 fh318 mutants exhibited reduced induction of the Nrf2 target genes in response to oxidative stress and electrophiles but were viable and fertile, and their embryos developed normally. The nrf2 fh318 larvae displayed enhanced sensitivity to oxidative stress and electrophiles, especially peroxides, and pretreatment with an Nrf2-activating compound, sulforaphane, decreased peroxide-induced lethality in the wild type but not nrf2 fh318 mutants, indicating that resistance to oxidative stress is highly dependent on Nrf2 functions. These results reveal an evolutionarily conserved role of vertebrate Nrf2 in protection against oxidative stress. Interestingly, there were no significant differences between wild-type and nrf2 fh318 larvae with regard to their sensitivity to superoxide and singlet oxygen generators, suggesting that the importance of Nrf2 in oxidative stress protection varies based on the type of reactive oxygen species (ROS). Oxidative stress causes damage to multiple cellular components, such as DNA, proteins, and lipids, and is implicated in various human pathological conditions, including cancer, neurodegeneration, and inflammatory diseases (37). Several proteins such as superoxide dismutase (SOD), catalase, glutathione peroxidase (Gpx), peroxiredoxin (Prdx), and the small thiol molecules glutathione (GSH) and thioredoxin (Txn), are directly involved in the removal of oxidative stress. Recent discoveries in the cellular antioxidant system gave rise to the novel concept of "indirect antioxidants," which act through the augmentation of cellular antioxidant capacity by enhancing the gene expression driven by the transcription factor Nrf2 (21, 22). Nrf2 is a basic-region leucine zipper (bZIP) transcription factor that heterodimerizes with small Maf proteins and binds to the antioxidant response element (ARE) within the regulatory region of its target genes (20,27). A variety of cytoprotective genes that encode phase 2 detoxifying enzymes and antioxidant proteins, such as glutathione S-transferases (GST), NAD(P)H:quinone oxidoreductase, and glutamate-cysteine ligase, are induced by Nrf2 via ARE sequences (14). Under basal conditions, Nrf2 is constantly degraded through the ubiquitin-proteasome pathway in a Keap1-dependent manner (28, 50). Upon exposure to electrophiles or oxidative stress, Nrf2 escapes from proteasomal degradation, accumulates in the nucleus, and transcriptionally activates its target genes.We previously isolated zebrafish homologs of Nrf2 and its regulator Keap1 genes (nrf2, keap1a, and keap1b) and demonstrated that ...

The red-beard sponge Clathria prolifera, which is widely distributed in the USA, has been widely used as a model system in cell biology and has been proposed as a suitable teaching tool on biology and environmental sciences. We undertook the first detailed microbiological study of this sponge on samples collected from the Chesapeake Bay. A combination of culture-based studies, denaturing gradient gel electrophoresis, and bacterial community characterization based on 16S rRNA gene sequencing revealed that C. prolifera contains a diverse assemblage of bacteria that is different from that in the surrounding water. C. prolifera individuals were successfully maintained in a flow-through or recirculation aquaculture system for over 6 months and shifts in the bacterial assemblages of sponges in aquaculture compared with wild sponges were examined. The proteobacteria, bacteroidetes, actinobacteria, and cyanobacteria represented over 90% of the species diversity present in the total bacterial community of the wild C. prolifera. Actinobacteria, cyanobacteria, and spirochetes were not represented in clones obtained from C. prolifera maintained in the aquaculture system although these three groups comprised ca. 20% of the clones from wild C. prolifera, showing a significant effect of aquaculture on the bacterial community composition. This is the first systematic characterization of the bacterial community from a sponge found in the Chesapeake Bay. Changes in sponge bacterial composition were observed in sponges maintained in aquaculture and demonstrate the importance of monitoring microbial communities when cultivating sponges in aquaculture systems.

Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and ageing. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in breast cancer (BC). The aim of this study was to investigate the frequency of mtDNA 4977 bp deletion in BC tissue and its association with clinical factors.We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 106 Vietnamese patients with BC by sequencing PCR products.The mtDNA 4977 bp deletion was significantly more frequent in normal tissue in comparison with paired cancer tissue. Moreover, the incidence of the 4977 bp deletion in BC tissue was significantly higher in patients with estrogen receptor (ER) positive as compared with ER negative BC tissue. Preliminary results showed, in cancerous tissue, a significantly higher incidence of novel deletions in the group of patients with lymph node metastasis in comparison with the patients with no lymph node metastasis.We have found 4977 bp deletion in mtDNA to be a common event in BC and with special reference to ER positive BC. In addition, the novel deletions were shown to be related to lymph node metastasis. Our finding may provide complementary information in prediction of clinical outcome including metastasis, recurrence and survival of patients with BC.

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