bluuebunny/crossref_metadata_2025_split huggingface dataset:
The drosophila ortholog of the endolysosomal membrane protein, endolyn, regulates cell proliferation
Authors: Zhou Guang‐Qian , Zhang Youyi , Ferguson David J.P. , Chen Sa , Rasmuson‐Lestander Åsa , Campbell Frederick C. , Watt Suzanne M. 
Published: August 2006

AbstractEndolyn (CD164) is a sialomucin that regulates the proliferation, adhesion, and migration of human haematopoietic stem and progenitor cells. This molecule is predominately localized in endocytotic compartments, where it may contribute to endolysosomal biogenesis and trafficking. In order to more closely define the function of endolyn from an evolutionary view‐point, we first analyzed endolyn orthologs in species ranging from insects, fish, and birds to mammals. The predicted molecular structures of the endolyn orthologs from these species are well conserved, particularly with respect to significant O‐linked glycosylation of the extracellular domain, and the high degree of amino acid similarities within their transmembrane and cytoplasmic domains, with the latter possessing the lysosomal target signal, YXXϕ. Focusing on Drosophila, our studies showed that the subcellular distribution of endolyn in non‐polarized Drosophila S2 cells resembles that of its human counterpart in hematopoietic cells, with its predominant localization being within intracellular vesicles, while a small fraction occurs on the cell surface. Both Y → A and L → A mutations in the YHTL motif perturbed the normal subcellular distribution of Drosophila endolyn. Interestingly, embryonic and early larval development was often arrested in endolyn‐deficient Drosophila mutants. This may partly be due to the role of endolyn in regulating cell proliferation, since knock‐down of endolyn expression in S2 cells resulted in up to 50% inhibition of cell growth, with a proportion of cells undergoing apoptosis. Taken together, these results demonstrate that endolyn is an evolutionarily conserved sialomucin fundamentally involved in cell proliferation in both the human and Drosophila melanogaster. J. Cell. Biochem. 99: 1380–1396, 2006. © 2006 Wiley‐Liss, Inc.
A proteomic approach to the identification of early molecular targets changed by L‐ascorbic acid in NB4 human leukemia cells
Authors: Park Seyeon , Lee Joomin , Yeom Chang‐Hwan 
Published: August 2006

AbstractThe pro‐oxidant effect of L‐ascorbic acid (LAA) is toxic to leukemia cells. LAA induces the oxidation of glutathione to its oxidized form (GSSG) and this is followed by a concentration‐dependent H2O2 accumulation, which occurs in parallel to the induction of apoptosis. To identify early protein targets of LAA in leukemia cells, we used a differential proteomics approach in NB4 human leukemia cells treated with 0.5 mM of LAA for 30 min. This exposure was determined to efficiently block cellular proliferation and to activate oxidative stress‐inducible apoptosis. We identified nine proteins that sensitively reacted to LAA treatment by using two‐dimensional (2‐D) gel electrophoresis and matrix‐assisted laser desorption ionization time‐of‐flight‐MS. A subunit of protein‐disulfide isomerase (a thiol/disulfide exchange catalyst) and immunoglobulin‐heavy‐chain binding protein (BiP, identical to Hsp70 chaperone) showed quantitative expression profile differences. A myeloid leukemia associated antigen protein (a tropomyosin isoform) showed changes in pI as a result of phosphorylation. Our studies demonstrate for the first time that the addition of LAA to cells results in an immediate change in the intracellular thiol/disulfide condition and that this includes an increase in the GSH oxidation with changes in the superfamily of thiol/disulfide exchange catalysts. These results suggest that LAA oxidizes intracellular reduced glutathione and modulates disulfide bond formation in proteins. J. Cell. Biochem. 99: 1628–1641, 2006. © 2006 Wiley‐Liss, Inc.
Downregulation of miR‐122 in the rodent and human hepatocellular carcinomas
Authors: Kutay Huban , Bai Shoumei , Datta Jharna , Motiwala Tasneem , Pogribny Igor , Frankel Wendy , Jacob Samson T. , Ghoshal Kalpana 
Published: August 2006

AbstractMicroRNAs (miRs) are conserved small non‐coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats‐fed folic acid, methionine, and choline‐deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age‐matched rats on the normal diet. While let‐7a, miR‐21, miR‐23, miR‐130, miR‐190, and miR‐17‐92 family of genes was upregulated, miR‐122, an abundant liver‐specific miR, was downregulated in the tumors. The decrease in hepatic miR‐122 was a tumor‐specific event because it did not occur in the rats switched to the folate and methyl‐adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR‐122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR‐122 expression was significantly (P = 0.013) reduced in 10 out of 20 tumors compared to the pair‐matched control tissues. These findings suggest that the downregulation of miR‐122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers. J. Cell. Biochem. 99: 671–678, 2006. © 2006 Wiley‐Liss, Inc.
Generation of reactive oxygen species is an early event in dolichyl phosphate‐induced apoptosis
Authors: Yokoyama Yoshiko , Nohara Kazunari , Okubo Tomoko , Kano Itsu , Akagawa Keisuke , Kano Kazutaka 
Published: August 2006

AbstractThe mechanism of induction of apoptosis by dolichyl phosphate (Dol‐P) was investigated in U937 cells. Studies using isolated mitochondria revealed that the respiratory complex II activity was almost completely inhibited by 20 µg/ml of Dol‐P but not by the same concentration of dolichol. Activities of complex I and III were also inhibited by Dol‐P, but nearly 50% of activity still remained at 20 µg/ml. Dol‐P induced release of cytochrome‐c from the isolated mitochondria. Fluorometric microtiter plate assay revealed that generation of reactive oxygen species (ROS) increased in a time‐dependent manner. Flow cytometric analysis also indicated that Dol‐P caused loss of mitochondrial membrane potential (Δψm) and increased ROS generation. The addition of the antioxidant pyrrolidine dithiocarbamate (PDTC) significantly inhibited Dol‐P‐induced ROS generation and activation of caspase‐3. A specific inhibitor of respiratory complex II, thenoyltrifluoroacetone (TTFA), increased ROS generation, potentially mimicking the consequence of inhibition of electron flow at complex II by Dol‐P in U937 cells. Electron microscopy revealed that mitochondria became swollen and spherical in shape by the treatment with Dol‐P. Neither the tyrosine kinase inhibitor k252a nor mitogen activated protein kinase/extracellular signal‐regulated kinase kinase (MEK) inhibitors PD98059 and U0126 inhibited the Dol‐P‐induced apoptosis. Together, these results suggest that the direct disruption of mitochondrial respiratory complexes and the consequent ROS generation play a critical role in the initiation of Dol‐P‐induced apoptosis. J. Cell. Biochem. 100: 349–361, 2007. © 2006 Wiley‐Liss, Inc.
Epigenetic modifiers promote efficient generation of neural‐like cells from bone marrow‐derived mesenchymal cells grown in neural environment
Authors: Alexanian Arshak R. 
Published: August 2006

AbstractUnderstanding mechanisms that govern cell fate decisions will lead to developing techniques for induction of adult stem cell differentiation to desired cell outcomes and, thus, production of an autologos source of cells for regenerative medicine. Recently, we demonstrated that stem cells derived from adult central nervous system or bone marrow grown with other cell lineages or with more undifferentiated cells sometimes take on those characteristics. This indicates that manipulating extracellular factors may be sufficient to alter some developmental restrictions regulated by the epigenetic system. In this study, using pharmacological agents that interfere with the main components of the epigenetic program such as DNA methylation and histone deacetylation, we induce high‐level expression of embryonic and neural stem cell (NSC) marker Sox2 in bone marrow‐derived mesenchymal stem cells (MSCs). Exposure of these modified cells to a neural environment via juxtacrine and paracrine interactions promote efficient generation of neural stem‐like cells as well as cells with neuronal and glial characteristics. We concluded that the manipulation strategy used in this study can be a useful method for efficient production of NSC‐like cells from MSCs. J. Cell. Biochem. 100: 362–371, 2007. © 2006 Wiley‐Liss, Inc.
Novel identification of peripheral dopaminergic D2 receptor in male germ cells
Authors: Otth Carola , Torres Mauricio , Ramírez Alfredo , Fernandez Juan Carlos , Castro Maite , Rauch M. Cecilia , Brito Mónica , Yañez Alejandro J. , Rodríguez‐Gil Joan‐Enric , Slebe Juan Carlos , Concha Ilona I. 
Published: August 2006

AbstractDopamine is a recognized modulator in the central nervous system (CNS) and peripheral organ functions. The presence of peripheral dopamine receptors outside the CNS has suggested an intriguing interaction between the nervous system and other functional systems, such as the reproductive system. In the present study we analyzed the expression of D2R receptors in rat testis, rat spermatogenic cells and spermatozoa, in different mammals. The RT‐PCR analysis of rat testis mRNA showed specific bands corresponding to the two dopamine receptor D2R (L and S) isoforms previously described in the brain. Using Western blot analysis, we confirmed that the protein is present in rat testis, isolated spermatogenic cells and also in spermatozoa of a range of different mammals, such as rat, mouse, bull, and human. The immunohistochemistry analysis of rat adult testis showed that the receptor was expressed in all germ cells (pre‐ and post‐meiotic phase) of the tubule with staining predominant in spermatogonia. Confocal analysis by indirect immunofluorescence revealed that in non‐capacitated spermatozoa of rat, mouse, bull, and human, D2R is mainly localized in the flagellum, and is also observed in the acrosomal region of the sperm head (except in human spermatozoa). Our findings demonstrate that the two D2 receptor isoforms are expressed in rat testis and that the receptor protein is present in different mammalian spermatozoa. The presence of D2R receptors in male germ cells implies new and unsuspected roles for dopamine signaling in testicular and sperm physiology. J. Cell. Biochem. 100: 141–150, 2007. © 2006 Wiley‐Liss, Inc.
Salvianolic acid B attenuates MMP‐2 and MMP‐9 expression in vivo in apolipoprotein‐E‐deficient mouse aorta and in vitro in LPS‐treated human aortic smooth muscle cells
Authors: Lin Shing‐Jong , Lee I‐Ta , Chen Yung‐Hsiang , Lin Feng‐Yen , Sheu Li‐Min , Ku Hung‐Hai , Shiao Ming‐Shi , Chen Jaw‐Wen , Chen Yuh‐Lien 
Published: August 2006

AbstractSalvianolic acid B (Sal B), a water‐soluble antioxidant derived from a Chinese medicinal herb, is believed to have multiple therapeutic and preventive against human vascular diseases, including atherosclerosis and restenosis. To elucidate the underlying cellular mechanisms, we produced hypercholesterolemia by feeding apo‐E‐deficient mice a 0.15% cholesterol diet and inflammation in human aortic smooth muscle cells (HASMCs) with the endotoxin lipopolysaccharide (LPS), focusing on the metallopreteinases MMP‐2 and MMP‐9, the relevant signal transduction pathways and the effects of Sal B. Immunohistochemical analyses indicated apo‐E‐deficient mice fed a 0.15% cholesterol diet for 12 weeks exhibited thickened intima and elevated levels of MMP‐2 and MMP‐9 in aortic sections, both of which were attenuated by 0.3% Sal B dietary supplement. Western blotting and zymography analyses indicated that unstimulated HASMCs exhibited basal levels of protein and activity levels for MMP‐2 and barely detectable levels for MMP‐9, both of which were markedly upregulated by LPS, which also induced cell migration. Sal B significantly attenuated upregulations of both MMPs as well as the LPS‐induced cell migration through the inactivation of MMP‐2 and MMP‐9 protein synthesis as well as the downregulation of the extracellular‐signal‐regulated kinase 1/2 (ERK1/2) and c‐Jun NH2‐terminal kinase (JNK). These results demonstrate that Sal B has anti‐migration properties on smooth muscle cells and may explain its anti‐atherosclerotic properties. This novel mechanism of action of Sal B, in addition to its previously reported inhibition of LDL oxidation, may help explain its efficacy in the treatment of atherosclerosis. J. Cell. Biochem. 100: 372–384, 2007. © 2006 Wiley‐Liss, Inc.
Establishment and characterization of an immortomouse‐derived odontoblast‐like cell line to evaluate the effect of insulin‐like growth factors on odontoblast differentiation
Authors: Catón Javier , Bringas Pablo , Zeichner‐David Margarita 
Published: August 2006

AbstractInsulin‐like growth factors (IGF‐I and IGF‐II) play important roles in regulating growth and differentiation of many different organs including teeth. The presence of these factors in the developing tooth has been demonstrated. In vitro studies using tooth explants grown in the presence of IGFs suggest that they promote differentiation of ameloblast and odontoblasts cells. This is achieved by inducing or repressing gene expression associated with these cells. Since some of the genes involved in tooth differentiation are expressed by both cells, to determine the effect of IGF on odontoblast cell differentiation we first need a cell line in which a controlled environment can be created. In this study, we report the establishment and characterization of an Immortomouse‐derived odontoblast‐like cell line. This conditional cell line can grow indefinitely under permissive conditions in the presence of INF‐γ at 33°C, differentiate into odontoblast‐like cells and produce a mineralized extracellular matrix when the INF‐γ is removed and cell maintained at 39°C. Addition of exogenous IGFs to the media results in an accelerated production of a mineralized matrix. This is the result of increased transcription of genes associated with bone mineralization while down regulating genes associated with dentin formation like DSPP. This data suggest that IGFs induce dental papillae mesenchyme cells to produce a bone‐like mineralized extracellular matrix. J. Cell. Biochem. 100: 450–463, 2007. © 2006 Wiley‐Liss, Inc.
Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell‐like
Authors: Jin Jun‐O , Park Hae‐Young , Kim Ja‐Woong , Park Joo‐In , Hong Young‐Seoub , Min Do Sik , Kwak Jong‐Young 
Published: August 2006

AbstractWe investigated whether phosphatidic acid (PA) can differentiate the promyelocytic leukemia (PML)‐retinoic acid receptor α (RARα)‐expressing acute promyelocytic leukemic cell line, NB4, to dendritic cell (DC)‐like cells. Dioctanoyl‐PA alone upregulated the expression of DC markers. The expression of DC markers on NB4 cells was potentiated by the overexpression of phospholipase D and upregulation was blocked by the addition of n‐butanol, an inhibitor of PA production. The expression of CD11c, CD83, and CCR7 in PA‐treated NB4 cells was further increased by tumor necrosis factor (TNF)‐α treatment. Increased functional capacities were also found in PA‐differentiated and TNF‐α‐activated NB4 cells with respect to changes in T‐cell proliferation, cytokine production, endocytic activity, and cytolytic capacity against undifferentiated NB4 cells. PA alone increased the phosphorylation of extracellular signal‐regulated kinase (ERK)‐1/2. The expression of DC markers was downregulated by PD98059, a specific inhibitor of ERK kinase or transient transfection of mutant‐ERK. The level of PML‐RARα fusion protein was decreased by PA treatment and PD98059 blocked the decrease of PML‐RARα. These results suggest that PA induces differentiation of NB4 cells into DC‐like cells and that the upregulation of antigen presenting cell markers is mediated by the activation of ERK and the downregulation of PML‐RARα levels. J. Cell. Biochem. 100: 191–203, 2007. © 2006 Wiley‐Liss, Inc.
Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio
Authors: Rucci Nadia , Rufo Anna , Alamanou Marina , Teti Anna 
Published: August 2006

AbstractMechanical unloading causes detrimental effects on the skeleton, but the underlying mechanisms are still unclear. We investigated the effect of microgravity on osteoblast ability to regulate osteoclastogenesis. Mouse osteoblast primary cultures were grown for 24 h at unit gravity or under simulated microgravity, using the NASA‐developed Rotating Wall Vessel bioreactor. Conditioned media (CM) from osteoblasts subjected to microgravity increased osteoclastogenesis and bone resorption in mouse bone marrow cultures. In these osteoblasts, the RANKL/OPG ratio was higher relative to 1g. Consistently, treatment with high concentrations of OPG‐inhibited osteoclastogenesis and bone resorption in the presence of CM arising from osteoblasts cultured under microgravity. Microgravity failed to affect osteoblast differentiation and function in the time frame of the experiment, as we found no effect on alkaline phosphatase mRNA and activity, nor on Runx2, osteocalcin, osteopontin, and collagen1A2 mRNA expression. In contrast, microgravity induced a time dependent increase of ERK‐1/2 phosphorylation, while phospho‐p38 and phospho‐JNK remained unchanged. Apoptosis, revealed by bis‐benzimide staining, was similar among the various gravity conditions, while it was increased under microgravity after treatment with the MEK‐1/2 inhibitor, PD98059, suggesting a protection role by ERK‐1/2 against cell death. In conclusion, microgravity is capable to indirectly stimulate osteoclast formation and activity by regulating osteoblast secretion of crucial regulatory factors such as RANKL and OPG. We hypothesize that this mechanism could contribute to bone loss in individuals subjected to weightlessness and other unloading conditions. J. Cell. Biochem. 100: 464–473, 2007. © 2006 Wiley‐Liss, Inc.
Hormonal induction of adipogenesis induces Skp2 expression through PI3K and MAPK pathways
Authors: Auld Corinth A. , Caccia Carla D. , Morrison Ron F. 
Published: August 2006

AbstractWe have previously shown that the F‐box protein, S‐phase kinase‐associated protein (Skp2) plays a mechanistic role in targeting the cell‐cycle inhibitor, p27 for degradation by the 26S proteasome during early stages of 3T3‐L1 adipocyte differentiation. Here, we demonstrate that protein levels of Skp2 and its accessory protein, Cks1 increased as density‐arrested preadipocytes re‐entered the cell cycle during clonal expansion, decreased with differentiation‐induced growth arrest, and became refractory to hormonal stimulation following the onset of terminal adipocyte differentiation. Component analysis revealed that while maximal Skp2/Cks1 protein accumulation required the complete differentiation cocktail, that insulin was principally involved. Skp2 mRNA accumulation was found to precede the increase in Skp2 protein and succeed the activation of Akt and Erk1/2, mediators of phosphatidylinositol‐3 kinase (PI3K) and mitogen‐activated protein kinase (MAPK) signal transduction pathways, respectively. Using specific inhibitors, we found that while activation of both pathways was required for maximal expression, PI3K signaling was primarily responsible for the increase in Skp2/Cks1 accumulation. The increase in Skp2 mRNA was notable 4 h following hormonal stimulation, plateaued by 12 h during mid‐G1 phase progression, and occurred without change to mRNA stability. We further demonstrate that luciferase activity, originating from a pGL3 vector containing 2.4 kb of the Skp2 promoter, increased 2.5‐fold with hormonal stimulation. This increase in promoter activity was markedly suppressed following PI3K and MAPK blockade. Deletion studies indicate that responsive elements were located within the proximal Skp2 promoter. These data demonstrate that Skp2 is transcriptionally regulated by PI3K and MAPK pathways as 3T3‐L1 preadipocytes transition from quiescence to proliferation during adipocyte hyperplasia. J. Cell. Biochem. 100: 204–216, 2007. © 2006 Wiley‐Liss, Inc.
Regulated expression of syndecan‐4 in rat calvaria osteoblasts induced by fibroblast growth factor‐2
Authors: Song Shu Jun , Cool Simon M. , Nurcombe Victor 
Published: August 2006

AbstractFibroblast growth factor‐2 (FGF2) is a member of a prominent growth factor family that drives proliferation in a wide variety of cell types, including osteoblasts. The binding and signal transduction triggered by these mitogens is dependent on glycosaminoglycan (GAG) sugars, particularly of the heparan sulfate (HS) class. These are secreted in proteoglycan (PG) complexes, some of which become FGF co‐receptors. The syndecans, the transmembrane forms of HSPG of which there are four members, act as multifunctional receptors for a variety of ligands involved in cell‐extracellular matrix (ECM) adhesion as well as growth factor binding. To understand the role of syndecans in developing osteoblasts, the effects of exogenous FGF2 on syndecan expression were examined using primary rat calvarial osteoblasts. All four syndecan mRNAs were expressed in the osteoblasts, although only syndecan‐4 was upregulated by FGF2 treatment in a dose‐dependent manner. This upregulation could be abrogated by pretreatment with the protein synthesis inhibitor cycloheximide, suggesting that the upregulation of syndecan‐4 by FGF2 is not a primary response. Osteoblast proliferation and mineralization were enhanced by exogenous FGF2 treatment, but could be specifically diminished by anti‐syndecan‐4 antibody pretreatment. This treatment also blocked FGF2‐induced extracellular signal‐regulated kinase activation, but not the expression of the bone‐specific transcription factor Runx2. These results demonstrate that mitogen‐triggered syndecan‐4 expression is an intrinsic part of the pathways subtending osteoblast proliferation and mineralization. J. Cell. Biochem. 100: 402–411, 2007. © 2006 Wiley‐Liss, Inc.
Increase in β1‐6 GlcNAc branching caused by N‐acetylglucosaminyltransferase V directs integrin β1 stability in human hepatocellular carcinoma cell line SMMC‐7721
Authors: Wang Liying , Liang Yulong , Li Zengxia , Cai Xiumei , Zhang Wen , Wu Guoqiang , Jin Jiawei , Fang Zhengyu , Yang Yong , Zha Xiliang 
Published: August 2006

AbstractIn this study, an enzymatic inactive mutant of GnT‐V (ΔcGnT‐V) was constructed and transfected in SMMC 7721 cell line. Integrin β1 in ΔcGnT‐V transfectants (Δc‐7721) showed attenuation of the number of β1‐6 GlcNAc branching, whereas those in wtGnT‐V transfectants (wt‐7721) presented a β1‐6 GlcNAc‐rich pattern. High integrin β1 expression was observed in wt‐7721 compared with mock cells (7721 cell transfected with the vector pcDNA3), while transfection of ΔcGnT‐V decreased the integrin β1 expression, despite of no significant changes on integrin β1 mRNA level in these cell lines. Pulse‐chase experiment showed that Integrin β1 in Δc‐7721 was prone to quick degradation and its half‐life was less than 3 h, on the contrary, the alleviating degradation of β1 subunit was observed in wt‐7721 where the β1 subunit half‐life was about 16 h, meanwhile, the degradation rate of β1 subunit in mock cells was in between, about 10 h. More effective in promoting cell migration toward fibronectin and invasion through Matrigel was observed in wt‐7721 while this was almost suppressed in Δc‐7721. Our results suggest that the addition of β1‐6 GlcNAc branching caused more fully glycosylated mature form on integrin β1 and inhibited β1 protein degradation. Glycosylation caused by GnT‐V directs integrin β1 stability and more delivery to plasma membrane, subsequently promotes Fn‐based cell migration and invasion. J. Cell. Biochem. 100: 230–241, 2007. © 2006 Wiley‐Liss, Inc.