Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1.

To survive in hostile environments, organisms activate stress-responsive transcriptional regulators that coordinately increase production of protective factors. Hypoxia changes cellular metabolism and thus activates redox-sensitive as well as oxygen-dependent signal transducers. We demonstrate that Sirtuin 1 (Sirt1), a redox-sensing deacetylase, selectively stimulates activity of the transcription factor hypoxia-inducible factor 2 alpha (HIF-2alpha) during hypoxia.

Synergistic upregulation of erythropoietin receptor (EPO-R) expression by sense and antisense EPO-R transcripts in the canine lung.

We previously found increased erythropoietin receptor (EPO-R) protein levels in vigorously growing canine lungs after pneumonectomy (PNX), suggesting a role for paracrine EPO signaling in lung growth and remodeling. Now we find that sense and antisense EPO-R transcripts (sEPO-R and asEPO-R, respectively) are concordantly up-regulated in the post-PNX remaining lung, leading to the hypothesis that sEPO-R and asEPO-R interactions enhance EPO signaling during lung growth. We cloned a canine asEPO-R cDNA, which is fully complementary to the sense strand of the EPO-R gene from 2.

Development of a mimotope-based vaccine against CD20 antigen.

CD20, a B-cell-specific protein, is a primary target for immunotherapy of B-cell lymphomas. We used a mimotopes of CD20 to construct vaccines for B-cell-related disorders. The immunogenicity of the vaccines was tested in BALB/c mice.

Postpneumonectomy lung expansion elicits hypoxia-inducible factor-1alpha signaling.

We (42) previously reported differential regulation of hypoxia-inducible factors (HIF-1alpha, -2alpha, and -3alpha) mRNA in canine lungs during normal maturation and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia. To test the hypothesis that lung expansion activates HIF signaling, we replaced the right lung of six adult foxhounds with inflated custom-shaped silicone prosthesis to keep the mediastinum in the midline and minimize lateral expansion of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the prosthesis was acutely deflated in three animals, causing the remaining lung to expand by 114%.

Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth.

We previously found increased expression of erythropoietin receptor (EPO-R) in peripheral dog lung during postnatal and postpneumonectomy (PNX) lung growth. To study the upstream regulation of EPO-R, we analyzed the expression of hypoxia-inducible factors (HIF)-1alpha, -2alpha, and -3alpha during postnatal lung growth in immature and mature (2.5 and 12 mo old, respectively) dogs and during compensatory lung growth 3 wk and 10 mo after right PNX.

HIF-2alpha regulates murine hematopoietic development in an erythropoietin-dependent manner.

Erythropoiesis in the adult mammal depends critically on erythropoietin, an inducible cytokine with pluripotent effects. Erythropoietin gene expression increases under conditions associated with lowered oxygen content such as anemia and hypoxia. HIF-1alpha, the founding member of the hypoxia-inducible factor (HIF) alpha class, was identified by its ability to bind and activate the hypoxia-responsive enhancer in the erythropoietin regulatory region in vitro.

SRY-related genes in the genome of the rice field eel (Monopterus albus).

The mammalian sex determining gene, SRY, is the founding member of the new growing family of Sox (SRY-like HMG-box gene) genes. Sox genes encode transcription factors with diverse roles in development, and a few of them are involved in sex determination and differentiation. We report here the existence of Sox genes in the rice field eel, Monopterus albus, and DNA sequence information of the HMG box region of five Sox genes.

Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption.

Tooth eruption requires the presence of the dental follicle, a loose connective tissue sac that surrounds each unerupted tooth. Early postnatally in the rat, the follicle secretes colony-stimulating factor-1 (CSF-1) and monocyte chemotactic protein-1 (MCP-1), chemotactic molecules that are probably responsible for the recruitment of mononuclear cells. These cells, in turn, fuse to form osteoclasts, which are required for alveolar bone resorption to form an eruption pathway.