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排序方式: 共有198条查询结果,搜索用时 203 毫秒
101.
Ozpolat B Akar U Steiner M Zorrilla-Calancha I Tirado-Gomez M Colburn N Danilenko M Kornblau S Berestein GL 《Molecular cancer research : MCR》2007,5(1):95-108
Programmed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. We investigated the role and the regulation of PDCD4 in the terminal differentiation of acute myeloid leukemia (AML) cells. Expression of PDCD4 was markedly up-regulated during all-trans retinoic acid (ATRA)-induced granulocytic differentiation in NB4 and HL60 AML cell lines and in primary human promyelocytic leukemia (AML-M3) and CD34(+) hematopoietic progenitor cells but not in differentiation-resistant NB4.R1 and HL60R cells. Induction of PDCD4 expression was associated with nuclear translocation of PDCD4 in NB4 cells undergoing granulocytic differentiation but not in NB4.R1 cells. Other granulocytic differentiation inducers such as DMSO and arsenic trioxide also induced PDCD4 expression in NB4 cells. In contrast, PDCD4 was not up-regulated during monocytic/macrophagic differentiation induced by 1,25-dihydroxyvitamin D3 or 12-O-tetradecanoyl-phorbol-13-acetate in NB4 cells or by ATRA in THP1 myelomonoblastic cells. Knockdown of PDCD4 by RNA interference (siRNA) inhibited ATRA-induced granulocytic differentiation and reduced expression of key proteins known to be regulated by ATRA, including p27(Kip1) and DAP5/p97, and induced c-myc and Wilms' tumor 1, but did not alter expression of c-jun, p21(Waf1/Cip1), and tissue transglutaminase (TG2). Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. In conclusion, our data suggest that PDCD4 expression contributes to ATRA-induced granulocytic but not monocytic/macrophagic differentiation. The PI3K/Akt/mTOR pathway constitutively represses PDCD4 expression in AML, and ATRA induces PDCD4 through inhibition of this pathway. 相似文献
102.
Akar U Ozpolat B Mehta K Fok J Kondo Y Lopez-Berestein G 《Molecular cancer research : MCR》2007,5(3):241-249
Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes. However, the role and the mechanisms that regulate TG2 expression remain elusive. Here, we provide evidence that protein kinase Cdelta (PKCdelta) regulates TG2 expression, which in turn inhibits autophagy, a type II programmed cell death, in pancreatic cancer cells that are frequently insensitive to standard chemotherapeutic agents. Rottlerin, a PKCdelta-specific inhibitor, and PKCdelta small interfering RNA (siRNA) down-regulated the expression of TG2 mRNA and protein and induced growth inhibition without inducing apoptosis in pancreatic cancer cells. Inhibition of PKCdelta by rottlerin or knockdown of TG2 protein by a TG2-specific siRNA resulted in a marked increase in autophagy shown by presence of autophagic vacuoles in the cytoplasm, formation of the acidic vesicular organelles, membrane association of microtubule-associated protein 1 light chain 3 (LC3) with autophagosomes, and a marked induction of LC3-II protein, important hallmarks of autophagy, and by electron microscopy. Furthermore, inhibition of TG2 by rottlerin or by the siRNA led to accumulation of green fluorescent protein (GFP)-LC3-II in autophagosomes in pancreatic cancer cells transfected with GFP-LC3 (GFP-ATG8) expression vector. Knockdown of Beclin-1, a specific autophagy-promoting protein and the product of Becn1 (ATG6), inhibited rottlerin-induced and TG2 siRNA-induced autophagy, indicating that Beclin-1 is required for this process. These results revealed that PKCdelta plays a critical role in the expression of TG2, which in turn regulates autophagy. In conclusion, these results suggest a novel mechanism of regulation of TG2 and TG2-mediated autophagy in pancreatic cancer cells. 相似文献
103.
Ozpolat B Akar U Zorrilla-Calancha I Vivas-Mejia P Acevedo-Alvarez M Lopez-Berestein G 《Apoptosis : an international journal on programmed cell death》2008,13(7):915-928
All-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) induce differentiation and apoptosis in acute promyelocytic leukemia (APL)
cells. Here we investigated the role and regulation of death-associated protein-5 (DAP5/p97/NAT1), a novel inhibitor of translational
initiation, in APL cell differentiation and apoptosis. We found that ATRA markedly induced DAP5/p97 protein and gene expression
and nuclear translocation during terminal differentiation of APL (NB4) and HL60 cells but not differentiation-resistant cells
(NB4.R1 and HL60R), which express very low levels of DAP5/p97. At the differentiation inducing concentrations, ATO (<0.5 μM),
dimethyl sulfoxide, 1,25-dihydroxy-vitamin-D3, and phorbol-12-myristate 13-acetate also significantly induced DAP5/p97 expression
in NB4 cells. However, ATO administered at apoptotic doses (1–2 μM) induced expression of DAP5/p86, a proapoptotic derivative
of DAP5/p97. ATRA and ATO-induced expression of DAP5/p97 was associated with inhibition of the phosphatidylinositol 3-kinase
(PI3K)/Akt pathway. Furthermore, DAP5/p97 expression was upregulated by inhibition of the PI3K/Akt/mammalian target of rapamycin
(mTOR) pathway via LY294002 and via rapamycin. Finally, knockdown of DAP5/p97 expression by small interfering RNA inhibited
ATRA-induced granulocytic differentiation and ATO-induced apoptosis. Together, our data reveal new roles for DAP5/p97 in ATRA-induced
differentiation and ATO-induced apoptosis in APL and suggest a novel regulatory mechanism by which PI3K/Akt/mTOR pathway inhibition
mediates ATRA- and ATO-induced expression of DAP5/p97.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
B. Ozpolat and U. Akar contributed equally. 相似文献
104.
105.
Monoclonal antibodies have been used to study the distribution of several proteins in cleavage and blastoderm stages of Drosophila melanogaster. These antigens are known to be associated with hnRNA-containing particles in tissue culture cells. Protein blotting shows that they are present in the embryo 1 hr after egg deposition. A redistribution from the cytoplasm into the somatic nuclei can be observed during developmental stage , one stage prior to the formation of the cellular blastoderm. Yolk nuclei become stained by these antibodies at about the same time. The shift into pole cell nuclei, however, occurs hr later, during the migration of these cells into the posterior midgut rudiment. 相似文献
106.
Dilek B. Donmez Sedat Kacar Ridvan Bagci Varol Sahinturk 《Journal of biochemical and molecular toxicology》2020,34(9)
Acrylamide is a food contaminant with a range of toxic effects. Carnosic acid (C20H28O4) is a phenolic compound found in plants and has many beneficial effects. In this study, we aimed at investigating the effect of carnosic acid on acrylamide‐induced liver damage. Rats (n = 7) were allotted to control, carnosic acid, acrylamide, acrylamide + carnosic acid groups. Animals were euthanized. Their blood was taken for biochemical analysis, and liver tissue was excised for morphological, immunohistochemical, and immunoblotting analyses. As a result, acrylamide reduced bodyweight, liver weight, catalase, and total antioxidant capacity levels but increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total oxidant status, oxidative stress index levels, Nrf2, and Keap1 protein levels. In addition, acrylamide disrupted liver histology leading to vascular congestion, cellular infiltration, necrotic cells, and so forth. Carnosic acid cotreatment ameliorated the altered biochemical parameters, liver histology, Nrf2, and Keap1 enzyme levels. In conclusion, carnosic acid has the potential to be used as a protective agent against acrylamide‐induced liver damage. 相似文献
107.
108.
Salih Terzioğlu Emin Zeki Başkent Fatih Sivrikaya Günay Çakir Ali Ihsan Kadioğullari Şağdan Başkaya Sedat Keleş 《Biologia》2010,65(5):843-852
This study was carried out in forestland of Camili Biosphere Reserve (CBR) area in NE Turkey. It was designed to evaluate
the consequences of disturbances on changes in secondary forest succession from 1985 to 2005 for monitoring forest plant biodiversity
changes and developing conservation strategies. The successional stages were mapped using Geographic Information System (GIS),
Global Positioning System (GPS), aerial photos and high resolution satellite images (IKONOS). The results showed that stable
stage decreased about 77.96% over the last 20-year time period. Although 701.6 ha conifer forests existed in competition and
reaction stages in 1985, none existed in 2005. In overall, about 33.23% of the area decreased, 42.36% did not change and 24.41%
increased in different seral stages. Consequently, 8.83% of the area decreased as a whole to indicate that the forest has
been developing from stable to nudation stage, that is to say, retrogressive succession is going on in the area. Forest structure
and its relationship with plant biodiversity along with its changes over time were determined using FRAGSTATS. We also investigated
spatio-temporal configuration of six secondary forest successional stages and generated structural diversity measures. These
measures revealed that the landscape has been fragmented, posing a danger to lose the important components of plant biodiversity.
Sustainable management of such degraded forests is of crucial importance for plant biodiversity conservation. In conclusion,
the study contributes to the development of a framework for effective conservation of plant biodiversity through plant biodiversity
integrated Multiple Use Forest Management (MUFM) plans by using the successional stages and plant biodiversity changes. 相似文献
109.
Akar A Akkaya EU Yesiladali SK Celikyilmaz G Cokgor EU Tamerler C Orhon D Cakar ZP 《Journal of industrial microbiology & biotechnology》2006,33(3):215-220
Microlunatus phosphovorus is an activated-sludge bacterium with high levels of phosphorus-accumulating activity and phosphate uptake and release activities.
Thus, it is an interesting model organism to study biological phosphorus removal. However, there are no studies demonstrating
the polyhydroxyalkanoate (PHA) storage capability of M. phosphovorus, which is surprising for a polyphosphate-accumulating organism. This study investigates in detail the PHA storage behavior
of M. phosphovorus under different growth conditions and using different carbon sources. Pure culture studies in batch-growth systems were conducted
in shake-flasks and in a bioreactor, using chemically defined growth media with glucose as the sole carbon source. A batch-growth
system with anaerobic–aerobic cycles and varying concentrations of glucose or acetate as the sole carbon source, similar to
enhanced biological phosphorus removal processes, was also employed. The results of this study demonstrate for the first time
that M. phosphovorus produces significant amounts of PHAs under various growth conditions and with different carbon sources. When the PHA productions
of all cultivations were compared, poly(3-hydroxybutyrate) (PHB), the major PHA polymer, was produced at about 20–30% of the
cellular dry weight. The highest PHB production was observed as 1,421 mg/l in batch-growth systems with anaerobic–aerobic
cycles and at 4 g/l initial glucose concentration. In light of these key results regarding the growth physiology and PHA-production
capability of M. phosphovorus, it can be concluded that this organism could be a good candidate for microbial PHA production because of its advantages
of easy growth, high biomass and PHB yield on substrate and no significant production of fermentative byproducts. 相似文献
110.
The Mcp element mediates stable long-range chromosome-chromosome interactions in Drosophila
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Chromosome organization inside the nucleus is not random but rather is determined by a variety of factors, including interactions between chromosomes and nuclear components such as the nuclear envelope or nuclear matrix. Such interactions may be critical for proper nuclear organization, chromosome partitioning during cell division, and gene regulation. An important, but poorly documented subset, includes interactions between specific chromosomal regions. Interactions of this type are thought to be involved in long-range promoter regulation by distant enhancers or locus control regions and may underlie phenomena such as transvection. Here, we used an in vivo microscopy assay based on Lac Repressor/operator recognition to show that Mcp, a polycomb response element from the Drosophila bithorax complex, is able to mediate physical interaction between remote chromosomal regions. These interactions are tissue specific, can take place between multiple Mcp elements, and seem to be stable once established. We speculate that this ability to interact may be part of the mechanism through which Mcp mediates its regulatory function in the bithorax complex. 相似文献