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971.
Chae YK Kang SK Kim MS Woo J Lee J Chang S Kim DW Kim M Park S Kim I Keam B Rhee J Koo NH Park G Kim SH Jang SE Kweon IY Sidransky D Moon C 《PloS one》2008,3(7):e2594
Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5. 相似文献
972.
ADPKD (Autosomal Dominant Polycystic Kidney Disease) is characterized by the progressive expansion of multiple cystic lesions in the kidneys. ADPKD is caused by mutations in Ed-pl. consider PKD1 and PKD2. Recently a relation between c-myc and the pathogenesis of ADPKD was reported. In addition, c-Myc is a downstream effector of PKD1. To identify the gene regulated by PKD2 and c-Myc, we performed gene expression profiling in PKD2 and c-Myc overexpressing cells using a human 8K cDNA microarray. NCAM (neuronal cell adhesion molecule) levels were significantly reduced in PKD2 overexpressing systems in vitro and in vivo. These results suggest that NCAM is an important molecule in the cystogenesis induced by PKD2 overexpression. 相似文献
973.
The objective of the present study was to identify mitochondrial components associated with the damage caused by iron to the rat heart. Decreased cell viability was assessed by increased presence of lactate dehydrogenase (LDH) in serum. To assess the functional integrity of mitochondria, Reactive Oxygen Species (ROS), the Respiratory Control Ratio (RCR), ATP and chelatable iron content were measured in the heart. Chelatable iron increased 15-fold in the mitochondria and ROS increased by 59%. Deterioration of mitochondrial function in the presence of iron was demonstrated by low RCR (46% decrease) and low ATP content (96% decrease). Using two dimensional gel electrophoresis (2DE), we identified alterations in 21 mitochondrial proteins triggered by iron overload. Significantly, expression of the alpha, beta, and d subunits of F(1)F(o) ATP synthase increased along with the loss of ATP. This suggests that the F(1)F(o) ATP synthase participates in iron metabolism. 相似文献
974.
975.
Lee K Song EH Kim HS Yoo JH Han HJ Jung MS Lee SM Kim KE Kim MC Cho MJ Chung WS 《The Journal of biological chemistry》2008,283(35):23581-23588
The mitogen-activated protein kinases (MAPKs) are key signal transduction molecules, which respond to various external stimuli. The MAPK phosphatases (MKPs) are known to be negative regulators of MAPKs in eukaryotes. We screened an Arabidopsis cDNA library using horseradish peroxidase-conjugated calmodulin (CaM), and isolated AtMKP1 as a CaM-binding protein. Recently, tobacco NtMKP1 and rice OsMKP1, two orthologs of Arabidopsis AtMKP1, were reported to bind CaM via a single putative CaM binding domain (CaMBD). However, little is known about the regulation of phosphatase activity of plant MKP1s by CaM binding. In this study, we identified two Ca(2+)-dependent CaMBDs within AtMKP1. Specific binding of CaM to two different CaMBDs was verified using a gel mobility shift assay, a competition assay with a Ca(2+)/CaM-dependent enzyme, and a split-ubiquitin assay. The peptides for two CaMBDs, CaMBDI and CaMBDII, bound CaM in a Ca(2+)-dependent manner, and the binding affinity of CaMBDII was found to be higher than that of CaMBDI. CaM overlay assays using mutated CaMBDs showed that four amino acids, Trp(453) and Leu(456) in CaMBDI and Trp(678) and Ile(684) in CaMBDII, play a pivotal role in CaM binding. Moreover, the phosphatase activity of AtMKP1 was increased by CaM in a Ca(2+)-dependent manner. Our results suggest that two important signaling pathways, Ca(2+) signaling and the MAPK signaling cascade, are connected in plants via the regulation of AtMKP1 activity. To our knowledge, this is the first report to show that the biochemical activity of MKP1 in plants is regulated by CaM. 相似文献
976.
977.
Song S Lee H Kam TI Tai ML Lee JY Noh JY Shim SM Seo SJ Kong YY Nakagawa T Chung CW Choi DY Oubrahim H Jung YK 《The Journal of cell biology》2008,182(4):675-684
Amyloid-beta (Abeta) neurotoxicity is believed to contribute to the pathogenesis of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates Abeta neurotoxicity. Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. Levels of endoplasmic reticulum (ER)-resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. Abeta increases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2-mediated cell death. Finally, we find that E2-25K/Hip-2-deficient cortical neurons are resistant to Abeta toxicity and to the induction of ER stress and caspase-12 expression by Abeta. E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress-mediated Abeta neurotoxicity. 相似文献
978.
Liu ZL Moon J Andersh BJ Slininger PJ Weber S 《Applied microbiology and biotechnology》2008,81(4):743-753
Furfural and 5-hydroxymethylfurfural (HMF) are representative inhibitors generated from biomass pretreatment using dilute
acid hydrolysis that interfere with yeast growth and subsequent fermentation. Few yeast strains tolerant to inhibitors are
available. In this study, we report a tolerant strain, Saccharomyces cerevisiae NRRL Y-50049, which has enhanced biotransformation ability to convert furfural to furan methanol (FM), HMF to furan di-methanol
(FDM), and produce a normal yield of ethanol. Our recent identification of HMF and development of protocol to synthesize the
HMF metabolic conversion product FDM allowed studies on fermentation metabolic kinetics in the presence of HMF and furfural.
Individual gene-encoding enzymes possessing aldehyde reduction activities demonstrated cofactor preference for NADH or NADPH.
However, protein extract from whole yeast cells showed equally strong aldehyde reduction activities coupled with either cofactor.
Deletion of a single candidate gene did not affect yeast growth in the presence of the inhibitors. Our results suggest that
detoxification of furfural and HMF by the ethanologenic yeast S. cerevisiae strain Y-50049 likely involves multiple gene mediated NAD(P)H-dependent aldehyde reduction. Conversion pathways of furfural
and HMF relevant to glycolysis and ethanol production were refined based on our findings in this study.
The mention of trade names or commercial products in this article is solely for the purpose of providing specific information
and does not imply recommendation or endorsement by the U.S. Department of Agriculture. 相似文献
979.
Seung Hyung Lee Prashant Shinde Jaeyong Choi Munsu Park Seho Ohh Ill Kyong Kwon Son Il Pak Byung Jo Chae 《Biological trace element research》2008,126(1):57-68
An experiment was conducted in weanling pigs (Landrace × Yorkshire × Duroc) to evaluate the effects of dietary iron levels on growth performance, hematological status, liver mineral concentration, fecal microflora, and diarrhea incidence. One hundred and forty-four piglets (initial BW 5.96 ± 0.93kg) were randomly allotted to one of the four dietary treatments on the basis of their body weights. The basal diets for each phase (phase 1: days0 to 14; phase 2: days15 to 28) were formulated to contain minimal Fe and then supplemented with gradient levels of Fe (0, 50, 100, and 250mg/kg) from ferrous sulfate. Feces were collected on days14 and 28 and used for the analysis of microbial count and trace minerals. Eight piglets from each treatment (two piglets per pen) were bled at 0, 7, 14, 21, and 28days to determine their hematological and plasma Fe status. In addition, two piglets from each pen (eight piglets per treatment) were killed at days14 and 28 to determine liver mineral concentrations. Pigs fed supplemental 250ppm Fe showed lowest overall average daily gain (linear, p = 0.036). Diarrhea incidence was linearly increased (p < 0.001) with supplemental Fe level. On days14, coliform population in normal feces was increased (p = 0.036) linearly with supplemental Fe level, and there were higher (p = 0.043) coliform population and lower (p < 0.001) Bifidobacterium spp. in the diarrhea feces. Supplemental Fe linearly (p < 0.05) improved the total red blood cells, hemoglobin, plasma, and liver (p = 0.109) Fe status of pigs and also increased (linear and quadratic, p < 0.001) the fecal excretion of Fe on days14 and 28. It is concluded that increasing the dietary iron levels in piglets improved their hematological status and liver Fe content; however, higher dietary Fe levels might also be associated with the increased diarrhea incidence. 相似文献
980.
Plant receptor proteins are involved in the signaling networks required for defense against pathogens. The novel pepper pathogen-induced gene CaMRP1 was isolated from pepper leaves infected with Xanthomonas campestris pv. vesicatoria (Xcv). This gene is predicted to encode a membrane-located receptor-like protein that has an N-terminal signal peptide and a C-terminal transmembrane helix. A CaMRP1-GFP fusion protein localized primarily to the plasma membrane of plant cells. Strong and early induction of CaMRP1 expression occurred following exposure of pepper plants to Xcv, Colletotricum coccodes, methyl jasmonate (MeJA) and wounding stress. Virus-induced gene silencing (VIGS) of CaMRP1 in pepper conferred enhanced basal resistance to Xcv infection, accompanied by induction of genes encoding basic PR1 (CaBPR1), defensin (CaDEF1) and SAR8.2 (CaSAR82A). In contrast, CaMRP1 overexpression (OX) in transgenic Arabidopsis plants resulted in increased disease susceptibility to Hyaloperonospora parasitica infection. Arabidopsis plants overexpressing CaMRP1 exhibited insensitivity to MeJA by causing reduced expression of MeJA-responsive genes. Overexpression also resulted in tolerance to NaCl and during salt stress, the expression of several abscisic acid-responsive genes was induced. Together, these results suggest that pepper CaMRP1 may belong to a new subfamily of membrane-located receptor-like proteins that regulate disease susceptibility, MeJA-insensitivity and salt tolerance. 相似文献