Erythropoietin (EPO) produced by the kidney and liver (in fetuses) stimulates erythropoiesis. In central nervous system, neurons express EPO receptor (EPOR) astrocytes produce EPO. has been shown to protect primary cultured from N -methyl- d -aspartate (NMDA) receptor-mediated glutamate toxicity. Here we report in vivo evidence that protects against ischemia-induced cell death. Infusion of into lateral ventricles gerbils prevented learning disability rescued hippocampal CA1 lethal ischemic...

Hypoxia-inducible factor-1 (HIF-1), a heterodimeric DNA binding complex composed of two basic-helix-loop-helix Per-AHR-ARNT-Sim proteins (HIF-1α and −1β), is key component widely operative transcriptional response activated by hypoxia, cobaltous ions, iron chelation. To identify regions HIF-1 subunits responsible for oxygen-regulated activity, we constructed chimeric genes in which portions coding sequence from were either linked to heterologous domain or encoded between such constitutive...

amines (19). Epo augments choline acetyltransferase in cul-

Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone insufficient to prevent neovascularization. Hence, it postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses activity, but its potential role in ocular angiogenesis not established.We measured both erythropoietin and levels the vitreous fluid 144 patients with use radioimmunoassay enzyme-linked immunosorbent assay. Vitreous...

Radioiodinated erythropoietin (Epo) was bound specifically to the cells of two non-erythroid clonal lines, PC12 and SN6, which expressed neuronal characteristics. The binding time-, cell number-, dose-dependent reversible. Although cloned Epo receptor from (derived rat adrenal medulla) identical that erythroid cells, significant differences in ligand properties between lineages were found; 1) had a single class sites with very low affinity (Kd = 16 nM), whereas classes different affinities...

Although erythropoietin (Epo) has been shown to possess <i>in vitro</i> angiogenic activity, its physiological significance not demonstrated. Normally angiogenesis does occur actively in adults but an exception is the female reproductive organ. In uterine endometrium, takes place for supporting endometrial growth that occurs during transition from diestrus estrous stage. This under control of 17β-estradiol (E₂), ovarian hormone, and can be mimicked by injection E₂...

Intracellular homeostasis for zinc is achieved through the coordinate regulation of specific transporters engaged in influx, efflux, and intracellular compartmentalization. We have identified a novel mammalian transporter, transporter 5 (ZnT-5), by virtue its similarity to ZRC1, <i>Saccharomyces cerevisiae</i>, member cation diffusion facilitator family. Human ZnT-5 (hZnT-5) cDNA encodes 765-amino acid protein with 15 predicted membrane-spanning domains. hZnT-5 was ubiquitously expressed all...

Cerebral amyloid angiopathy (CAA) due to beta-amyloid (Abeta) is one of the specific pathological features familial Alzheimer's disease. Abeta mainly consisting 40- and 42-mer peptides (Abeta40 Abeta42) exhibits neurotoxicity aggregative abilities. All variants Abeta40 Abeta42 found in CAA were synthesized a highly pure form examined for PC12 cells ability. mutants at positions 22 23 showed stronger than wild-type Abeta40. Similar tendency was observed whose 50-200 times that corresponding...

Amyloid fibrils in Alzheimer's disease mainly consist of 40- and 42-mer β-amyloid peptides (Aβ40 Aβ42) that exhibit aggregative ability neurotoxicity. Although the aggregates Aβ are rich intermolecular β-sheet, precise secondary structure remains unclear. To identify amino acid residues involved β-sheet formation, 34 proline-substituted mutants Aβ42 were synthesized their neurotoxicity on PC12 cells examined. Prolines rarely present whereas they easily accommodated β-turn as a Pro-X corner....

Zinc is an essential component for the catalytic activity of numerous zinc-requiring enzymes. However, until recently little has been known about molecules involved in pathways required supplying zinc to these We showed (Suzuki, T., Ishihara, K., Migaki, H., Matsuura, W., Kohda, A., Okumura, Nagao, M., Yamaguchi-Iwai, Y., and Kambe, T. (2005) J. Biol. Chem. 280, 637-643) that transporters, ZnT5 ZnT7, are activation enzymes, alkaline phosphatases (ALPs), by transporting into lumens Golgi...

Numerous proteins are properly folded by binding with zinc during their itinerary in the biosynthetic-secretory pathway. Several transporters have been implicated entry into secretory compartments from cytosol, but precise roles poorly understood. We report here that two (ZnT5 and ZnT7) localized apparatus responsible for loading to alkaline phosphatases (ALPs) glycosylphosphatidylinositol-anchored membrane exposed extracellular site. Disruption of ZnT5 gene DT40 cells decreased ALP activity...

Amyloid fibrils mainly consist of 40-mer and 42-mer peptides (Aβ40, Aβ42). Aβ42 is believed to play a crucial role in the pathogenesis Alzheimer's disease because its aggregative ability neurotoxicity are considerably greater than those Aβ40. The Aβ involving generation free radicals closely related S-oxidized radical cation Met-35. However, cation's origin mechanism stabilization remain unclear. Recently, structural models fibrillar Aβ40 based on systematic proline replacement have been...

Erythropoietin (Epo) produced by the kidney regulates erythropoiesis. Recent evidence suggests that Epo in cerebrum prevents neuron death and uterus induces estrogen (E 2 )-dependent uterine angiogenesis. To elucidate how expression is regulated these tissues, ovariectomized mice were given E and/or exposed to hypoxia, temporal patterns of mRNA levels examined. elevated markedly within 4 h after exposure hypoxia. Although level decreased 8 despite continuous high was sustained for ≥24 h,...

The majority of CDF/ZnT zinc transporters form homo-oligomers. However, ZnT5, ZnT6, and their orthologues hetero-oligomers in the early secretory pathway where they load onto zinc-requiring enzymes maintain functions. details this hetero-oligomerization remain to be elucidated, much more is known about homo-oligomerization that occurs other family proteins. Here, we addressed issue using co-immunoprecipitation experiments, mutagenesis, chimera studies hZnT5 hZnT6 chicken DT40 cells deficient...

Nuclear export of mRNA is an essential process for eukaryotic gene expression. The TREX complex couples expression from transcription and splicing to export. Sub2, a core component the in yeast, has diversified humans two closely related RNA helicases, UAP56 URH49. Here, we show that URH49 forms novel URH49-CIP29 complex, termed AREX (alternative export) whereas human complex. mRNAs regulated by these helicases are different at genome-wide level. sets target contain distinct subsets key...

The SLC39A family of zinc transporters can be divided into four subfamilies (I, II, LIV-1, and gufA) in vertebrates, but studies their functions have been restricted exclusively to members II LIV-1. In this study, we characterized SLC39A9 (ZIP9), the only member subfamily I vertebrates. Confocal microscopy demonstrated that transiently expressed, HA-tagged human ZIP9 (hZIP9-HA) was localized trans-Golgi network regardless status. Disruption gene DT40 cells did not change growth rate,...

The accumulating evidence that erythropoietin and receptor are expressed in various non-haematopoietic organs suggests signalling might be involved the growth of tumours, but this possibility has never been examined. We found mRNAs for malignant tumours female reproductive organs, where levels higher than normal tissues. Furthermore, tumour cells capillary endothelium showed immunoreactivity. To investigate role erythropoietin/erythropoietin pathway these we injected mouse monoclonal...

We have recently shown that malignant tumours from the ovary and uterus expressed erythropoietin (Epo) its receptor (EpoR), deprivation of Epo signal in tumour blocks induced death cells capillary endothelial vitro (Yasuda et al, submitted). These results prompted us to examine effect Epo-signal withdrawal on vivo. RT-PCR analysis demonstrated expression mRNAs for EpoR transplants uterine ovarian nude mice. Then we injected locally anti-Epo antibody or soluble form into transplants. At 12 h,...

Zinc transporters play important roles in a wide range of biochemical processes. Here we report an function ZnT5/ZnT6 hetero-oligomeric complexes the secretory pathway. The activity human tissue-nonspecific alkaline phosphatase (ALP) expressed ZnT5–ZnT7–/– cells was significantly reduced compared with that wild-type as case endogenous chicken ALP activity. inactive degraded by proteasome-mediated degradation without being trafficked to plasma membrane. showed exacerbation unfolded protein...