Matches in Nanopublications for { ?s <http://www.w3.org/ns/prov#value> ?o ?g. }
- _5 value "IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells" provenance.
- _3 value "Starvation and streptozotocin-induced diabetes cause decreases in PDP2 mRNA abundance, PDP2 protein amount, and PDP activity in rat heart and kidney. Refeeding and insulin treatment effectively reversed these effects of starvation and diabetes, respectively." provenance.
- _7 value "hetero-dimerization of MAX with other HLH-LZ proteins, such as MAD, Mxi-1 and Mnt, which are antagonists of c-MYC-induced transformation" provenance.
- _4 value "Surprisingly, Skp2 enhances c-Myc-induced S phase transition and activates c-Myc target genes in a Myc-dependent manner." provenance.
- _3 value "Table 3. Transcripts upregulated by aldosterone" provenance.
- _7 value "We show that SMRT and DAX-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases." provenance.
- _6 value "We show that SMRT and DAX-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases." provenance.
- _6 value "We show that SMRT and DAX-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases." provenance.
- _4 value "Treatment of melanoma cells with either TRAIL or U0126, a MEK inhibitor could not induce significant reduction in XIAP expression levels, but when the agents were combined there was marked decrease in the percentage of XIAP-positive cells, suggesting that TRAIL-induced XIAP was upregulated by ERK2." provenance.
- _5 value "These data suggest that RhoE induces stress fiber disassembly by directly binding ROCK I and inhibiting it from phosphorylating downstream targets." provenance.
- _3 value "hypoxia rapidly and reversibly triggers hypophosphorylation of mTOR and its effectors 4E-BP1, p70S6K, rpS6, and eukaryotic initiation factor 4G." provenance.
- _4 value "As soon as these tumours are re-vascularized, they become extremely aggressive - patients who are diagnosed with glioblastomas have a median survival of only 1 year. In summary, microvessel density is only a useful prognostic marker for some cancer types. Overcoming angiogenic dependency? In contrast to tumour cells that are, by nature, genetically unstable and heterogeneous, endothelial cells are normal diploid cells that do not acquire mutations, and therefore should not become resistant to therapy. This rationale stimulated researchers to dream of a pantumour therapy focused on blood-vessel ablation. This dream, however, seems to be naive. Both animal and preliminary human clinical trials revealed that different tumours respond differently to anti-angiogenic therapy. Do these differences in response depend on the type or amount of angiogenic molecules that are expressed, or on other intrinsic tumour-cell characteristics, such as oncogene expression or resistance to hypoxia? Does anti-angiogenic therapy simply select for tumour cells that can grow at very low oxygen levels,without initiating neoangiogenesis or that use alternative pathways to circumvent neovascularization? Initial findings indicate that these effects might indeed happen in some tumour types.Anti-VEGF therapy in a rat model of glioblastoma resulted in decreased tumour vessel density and increased apoptosis.However, treatment also led to the increased co-option of existing blood vessels, circumventing the necessity of the tumour to initiate angiogenesis62. Examples of emerging resistance to anti-angiogenesis therapy include studies that showed that glioblastomas become resistant to TSP1 therapy63, renal-cell carcinomas become insenstitive to thalidomide64 and tumours that lose p53 expression become less responsive to combinations of low-dose cytotoxic and anti-angiogenic agents65." provenance.
- _3 value "activators of endothelial-cell proliferation and migration are mainly receptor tyrosine kinase ligands, such as VEGF, FGFs, PDGF and EGF, but can also be of very different origin, such as lysophosphatidic acid" provenance.
- _6 value "Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCtheta primarily abrogates NFAT transactivation" provenance.
- _6 value "Modified assertion" provenance.
- _4 value "ZD1839 (\"Iressa\") is an adenosine triphosphate-competitive inhibitor specific to the EGFR tyrosine kinase currently under evaluation as a chemotherapeutic agent in HNSCC." provenance.
- _4 value "The reduced p27Kip1 protein expression level in PGI-overexpressing cells could be restored to control levels by treatment with proteasome inhibitor." provenance.
- _3 value "Tables 2-7. Some differentially expressed genes (P <= 0.01 by t-test or rank sum test, q < 10%, and >= 1.3-fold difference) ratio old/young upregulated" provenance.
- _3 value "Tables 2-7. Some differentially expressed genes (P <= 0.01 by t-test or rank sum test, q < 10%, and >= 1.3-fold difference) ratio old/young upregulated" provenance.
- _3 value "Tables 2-7. Some differentially expressed genes (P <= 0.01 by t-test or rank sum test, q < 10%, and >= 1.3-fold difference) ratio old/young upregulated" provenance.
- _3 value "downregulated" provenance.
- _3 value "downregulated" provenance.
- _3 value "downregulated" provenance.
- _6 value "Phosphorylation at Thr 125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation" provenance.
- _3 value "To identify genes that might be associated with sensitivity to this drug we used a cDNA microarray representing 23,040 genes to analyze expression profiles of the 13 xenografts and identified 114 genes whose expression levels correlated significantly with sensitivity of the tumors to ZD1839." provenance.
- _3 value "To identify genes that might be associated with sensitivity to this drug we used a cDNA microarray representing 23,040 genes to analyze expression profiles of the 13 xenografts and identified 114 genes whose expression levels correlated significantly with sensitivity of the tumors to ZD1839." provenance.
- _3 value "To identify genes that might be associated with sensitivity to this drug we used a cDNA microarray representing 23,040 genes to analyze expression profiles of the 13 xenografts and identified 114 genes whose expression levels correlated significantly with sensitivity of the tumors to ZD1839." provenance.
- _3 value "To identify genes that might be associated with sensitivity to this drug we used a cDNA microarray representing 23,040 genes to analyze expression profiles of the 13 xenografts and identified 114 genes whose expression levels correlated significantly with sensitivity of the tumors to ZD1839." provenance.
- _3 value "To identify genes that might be associated with sensitivity to this drug we used a cDNA microarray representing 23,040 genes to analyze expression profiles of the 13 xenografts and identified 114 genes whose expression levels correlated significantly with sensitivity of the tumors to ZD1839." provenance.
- _6 value "alpha2beta1 is upregulated by VEGF, alphaVbeta3 and alpha5beta1 are not, but instead are induced by bFGF, TNF and other angiogenic cytokines" provenance.
- _5 value "alphaVbeta3 integrin, which is not expressed on resting quiescent endothelial cells but is markedly upregulated in endothelial cells at sites of angiogenesis, including wound repair and angiogenesis induced in response to human breast tumor cells" provenance.
- _3 value "We originally identified N4WBP5A as an unknown expressed sequence tag (AA770150) represented in a cDNA microarray analysis that was up-regulated upon activation of T cells and inhibited by cell treatment with the calcineurin phosphatase inhibitors, cyclosporine (CsA) and tacrolimus (FK506). " provenance.
- _5 value "This report describes the identification of a consensus ERK phosphorylation site in the linker region of Smad4 at Thr276." provenance.
- _3 value "Ovariectomized rats treated for 3 days twice daily s.c. with estradiol-17beta (2.5 microg/injection), progesterone (2 mg/injection), and the combination of estradiol-17beta and progesterone (same doses as above) were also examined for the expression of various receptor components. progesterone caused significant increases in CRLR (P < 0.001), RAMP1 (P < 0.05), and RAMP2 (P <" provenance.
- _3 value "Because of their function as regulators of proliferation and apoptosis, CD24, insulin-like growth factor-binding protein 2, and Fas/Fas ligand were examined further by immunohistochemical expression and tissue localization analysis. Our analysis confirms a contrasting regulation of these gene products by ovariectomy and estrogen treatment." provenance.
- _4 value "Here we show that CRIM1 can interact with both BMP4 and BMP7 via the CRR-containing portion of the protein and in so doing acts as an antagonist in three ways. CRIM1 binding of BMP4 and -7 occurs when these proteins are co-expressed within the Golgi compartment of the cell and leads to (i) a reduction in the production and processing of preprotein to mature BMP, (ii) tethering of pre-BMP to the cell surface, and (iii) an effective reduction in the secretion of mature BMP." provenance.
- _3 value "We have recently shown that transient expression of 10-formyltetrahydrofolate dehydrogenase (FDH) strongly inhibits proliferation of several cancer cell lines and ultimately results in cell death. expression results in initiation of apoptosis beginning 24 h post-induction." provenance.
- _5 value "Infection of the cultures with H. pylori (strain 26695) induced NF-kappa B activity in cells transfected with TLR2 and TLR5, but not TLR4." provenance.
- _3 value "in the liver of mice, SCALD is suppressed by fasting and induced by refeeding, consistent with regulation by Srebps" provenance.
- _3 value "TSP1/hep I-induced focal adhesion disassembly is associated with reduced chemotaxis to basic fibroblast growth factor (bFGF) but enhanced chemotaxis to acidic (a)FGF, suggesting differential modulation of growth factor-induced migration." provenance.
- _3 value "PED/PEA-15 was phosphorylated by Akt Akt phosphorylation of PED/PEA-15 occurred mainly at Ser(116). PED/PEA-15 specifically bound Akt, independently of Akt activity." provenance.
- _5 value "Modified assertion" provenance.
- _5 value "ALK3 and Alk6 are activated by BMP2, BMP4, and BMP7 whereas ALK2 binds BMP6 and BMP7" provenance.
- _5 value "table II - genes upregulated in TTF-1 mutant mice" provenance.
- _5 value "table II - genes upregulated in TTF-1 mutant mice" provenance.
- _5 value "table II - genes upregulated in TTF-1 mutant mice" provenance.
- _5 value "table II - genes upregulated in TTF-1 mutant mice" provenance.
- _5 value "table III - genes downregulated in TTF-1 mutant mice" provenance.
- _5 value "table III - genes downregulated in TTF-1 mutant mice" provenance.
- _5 value "table III - genes downregulated in TTF-1 mutant mice" provenance.
- _5 value "table III - genes downregulated in TTF-1 mutant mice" provenance.
- _5 value "table III - genes downregulated in TTF-1 mutant mice" provenance.
- _5 value "table III - genes downregulated in TTF-1 mutant mice" provenance.
- _4 value "IGF1 incudes keratinocyte migration via RAC1" provenance.
- _5 value "Although NRF-1 expression is decreased only in diabetic subjects, expression of both PPAR gamma coactivator 1-alpha and-beta (PGC1-alpha/PPARGC1 and PGC1-beta/PERC), coactivators of NRF-1 and PPAR gamma-dependent transcription, is decreased in both diabetic subjects and family history-positive nondiabetic subjects." provenance.
- _4 value "To study the interdependence of the two proteins, we generated a rat cell line that expressed a dexamethasone-inducible c-H-ras construct. Induction of c-H-Ras expression was followed by rapid upregulation of survivin. Conversely, downregulation of the oncoprotein resulted in prompt reduction of survivin to baseline value." provenance.
- _4 value "Although there are now four known adenosine receptors, and the nomenclature has been changed and refined, the early classification scheme still mirrors the generally accepted profile of adenosine receptor G protein coupling (Table 1)" provenance.
- _6 value "Although there are now four known adenosine receptors, and the nomenclature has been changed and refined, the early classification scheme still mirrors the generally accepted profile of adenosine receptor G protein coupling (Table 1)" provenance.
- _4 value "SphK2 enhanced apoptosis in diverse cell types and also suppressed cellular proliferation." provenance.
- _3 value "The phytochemical resveratrol, found in grapes, berries and peanuts, has been found to possess cancer chemopreventive effects by inhibiting diverse cellular events associated with tumour initiation, promotion and progression. Resveratrol is also a phyto-oestrogen, binds to and activates oestrogen receptors that regulate the transcription of oestrogen-responsive target genes such as the breast cancer susceptibility genes BRCA1 and BRCA2. We investigated the effects of resveratrol on BRCA1 and BRCA2 expression in human breast cancer cell lines (MCF7, HBL 100 and MDA-MB 231) using quantitative real-time RT-PCR, and by perfusion chromatography of the proteins. All cell lines were treated with 30 microM resveratrol. The expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found. These data indicate that resveratrol at 30 micro M can increase expression of genes involved in the aggressiveness of human breast tumour cell lines." provenance.
- _5 value "BBS stimulation of GRP-R resulted in the up-regulation of IL-8 and VEGF expression through a NF kappa B-dependent pathway" provenance.
- _3 value "A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts)" provenance.
- _3 value "A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts)" provenance.
- _4 value "Remarkably, A-CREB severely disrupted expression of IRS2, an insulin signaling pathway component that is shown here to be a direct target for CREB action in vivo As induction of IRS2 by cAMP enhanced activation of the survival kinase Akt in response to insulin and IGF-1, our results demonstrate a novel mechanism by which opposing pathways cooperate in promoting cell survival." provenance.
- _3 value "Gene array experiments indicated that GM-CSF selectively restored a variety of dexamethasone-suppressed, LPS-inducible genes relevant for innate immunity." provenance.
- _3 value "400, 800 mg/kg/day treatment gene changes" provenance.
- _3 value "400, 800 mg/kg/day treatment gene changes" provenance.
- _3 value "List of genes changed upon Clofibrate (800mg/kg/day) treatment." provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. " provenance.
- _3 value "Fibrate class hypolipidemic drugs such as ciprofibrate activate the peroxisome proliferator-activated receptor-alpha (PPARalpha), which is involved in processes including lipid metabolism and hepatocyte proliferation in rodents. We examined the effects of ciprofibrate (50 mg/kg body wt per day for 60 days) on liver gene expression in rats using cDNA microarrays. The 60-day dosing period was chosen to elucidate both the metabolic and proliferative actions of this substance, while avoiding confounding effects from the hepatic carcinogenesis seen during more long-term stimulation. Ciprofibrate changed the expression of many genes including previously known PPARalpha agonist-responsive genes involved in processes such as lipid metabolism and inflammatory responses. In addition, many novel candidate genes involved in sugar metabolism, transcription, signal transduction, cell proliferation, and stress responses appeared to be differentially regulated in ciprofibrate-dosed rats. Ciprofibrate also resulted in significant increases in liver weight and hepatocyte proliferation. The cDNA microarray results were confirmed by Northern blot analysis for selected genes. This study thus identifies many genes that appear to be differentially regulated in ciprofibrate-dosed rats, and some of these are potential targets of PPARalpha. The functional diversity of these candidate genes suggests that most of them are likely to be differentially regulated as indirect consequence of the many processes affected by ciprofibrate in rodent liver. Although caution is advisable in the interpretation of genome-wide expression data, the genes identified in the present study provide candidates for further studies that may give new insight into the mechanisms of action of peroxisome proliferators." provenance.
- _3 value "Fibrate class hypolipidemic drugs such as ciprofibrate activate the peroxisome proliferator-activated receptor-alpha (PPARalpha), which is involved in processes including lipid metabolism and hepatocyte proliferation in rodents. We examined the effects of ciprofibrate (50 mg/kg body wt per day for 60 days) on liver gene expression in rats using cDNA microarrays. The 60-day dosing period was chosen to elucidate both the metabolic and proliferative actions of this substance, while avoiding confounding effects from the hepatic carcinogenesis seen during more long-term stimulation. Ciprofibrate changed the expression of many genes including previously known PPARalpha agonist-responsive genes involved in processes such as lipid metabolism and inflammatory responses. In addition, many novel candidate genes involved in sugar metabolism, transcription, signal transduction, cell proliferation, and stress responses appeared to be differentially regulated in ciprofibrate-dosed rats. Ciprofibrate also resulted in significant increases in liver weight and hepatocyte proliferation. The cDNA microarray results were confirmed by Northern blot analysis for selected genes. This study thus identifies many genes that appear to be differentially regulated in ciprofibrate-dosed rats, and some of these are potential targets of PPARalpha. The functional diversity of these candidate genes suggests that most of them are likely to be differentially regulated as indirect consequence of the many processes affected by ciprofibrate in rodent liver. Although caution is advisable in the interpretation of genome-wide expression data, the genes identified in the present study provide candidates for further studies that may give new insight into the mechanisms of action of peroxisome proliferators." provenance.
- _3 value "Fibrate class hypolipidemic drugs such as ciprofibrate activate the peroxisome proliferator-activated receptor-alpha (PPARalpha), which is involved in processes including lipid metabolism and hepatocyte proliferation in rodents. We examined the effects of ciprofibrate (50 mg/kg body wt per day for 60 days) on liver gene expression in rats using cDNA microarrays. The 60-day dosing period was chosen to elucidate both the metabolic and proliferative actions of this substance, while avoiding confounding effects from the hepatic carcinogenesis seen during more long-term stimulation. Ciprofibrate changed the expression of many genes including previously known PPARalpha agonist-responsive genes involved in processes such as lipid metabolism and inflammatory responses. In addition, many novel candidate genes involved in sugar metabolism, transcription, signal transduction, cell proliferation, and stress responses appeared to be differentially regulated in ciprofibrate-dosed rats. Ciprofibrate also resulted in significant increases in liver weight and hepatocyte proliferation. The cDNA microarray results were confirmed by Northern blot analysis for selected genes. This study thus identifies many genes that appear to be differentially regulated in ciprofibrate-dosed rats, and some of these are potential targets of PPARalpha. The functional diversity of these candidate genes suggests that most of them are likely to be differentially regulated as indirect consequence of the many processes affected by ciprofibrate in rodent liver. Although caution is advisable in the interpretation of genome-wide expression data, the genes identified in the present study provide candidates for further studies that may give new insight into the mechanisms of action of peroxisome proliferators." provenance.
- _3 value "OxLDL can promote immune activation as determined by enhanced secretion of IFN-gamma and TNF by immune competent cells OxLDL had the capacity to induce IL-12, IL-10 and TNF" provenance.
- _5 value "Although phosphatidylinositol 3-kinase pathway inhibition by LY294004 blocked both PHAS-1 Ser-65 and Thr-70 phosphorylation (3.8 +/- 0.1 versus 0.8 +/- 0.1 and 3.2 +/- 0.2 versus 1.0 +/- 0.01, respectively), protein phosphatase 2A inhibition by okadaic acid selectively increased (3.3 +/- 0.1 versus 5.2 +/- 0.1) and p38 mitogen-activated protein kinase inhibition by SB203580 selectively decreased (3.8 +/- 0.1 versus 1.4 +/- 0.3) Ser-65 phosphorylation." provenance.
- _4 value "From Full Paper Introduction The TLRs agonist include LPS for Tlr4, peptidglycan for Tlr2 and 6..." provenance.
- _3 value "Heme oxygenase-1 (HO-1) is a stress response protein that is highly inducible under various conditions, such as oxidative or heat stress." provenance.
- _4 value "BTC induced phosphorylation of all four EGF receptors present on HTASMCs: ErbB1, ErbB2, ErbB3, and ErbB4." provenance.
- _3 value "We examined how BTC and AR induced DNA synthesis activity in primary cultures of human thoracic aortic smooth muscle cells (HTASMCs)." provenance.
- _3 value " View this table: [in this window] [in a new window] TABLE 1 Summary of the various functions of HO isoforms, their tissue distribution, and gene regulation Maines et al. (1986) were the first to report the identification of a second form of HO from rat liver microsomes, designated HO-2. Only recently, a third isoform, HO-3, was discovered (McCoubrey et al., 1997). HO-1 and HO-2 share little similarity in amino acid sequence (40%), whereas the HO-2 and HO-3 isoform are far more homologous (90%). All HO isoforms are highly conserved among species in evolution. HO is expressed in virtually all life forms; in prokaryotic bacteria as well as in fungi, plants, and humans, regulating a wide spectrum of cellular processes (Terry et al., 2002). The homology between rat, mouse, and human is for HO-1 and HO-2 proteins higher than 80% and 90%, respectively. Under normal physiological conditions, most cells express low or undetectable levels of HO-1 protein, whereas HO-2 proteins are constitutively expressed. HO-3 protein expression awaits further characterization. HO-2 transcription is only up-regulated by few agents, such as opiates and adrenal glucocorticoids (Li and David Clark, 2000; Liu et al., 2000). HO-1 gene expression is highly inducible by more diverse stimuli than any other enzyme described to date (Maines, 1997) and involves a multitude of signaling pathways (Table 2) (Immenschuh and Ramadori, 2000). HO-1 expression is mainly regulated at the transcriptional level. View this table: [in this window] [in a new window] TABLE 2 Selection of different inducers of HO-1 gene expression " provenance.
- _3 value " View this table: [in this window] [in a new window] TABLE 1 Summary of the various functions of HO isoforms, their tissue distribution, and gene regulation Maines et al. (1986) were the first to report the identification of a second form of HO from rat liver microsomes, designated HO-2. Only recently, a third isoform, HO-3, was discovered (McCoubrey et al., 1997). HO-1 and HO-2 share little similarity in amino acid sequence (40%), whereas the HO-2 and HO-3 isoform are far more homologous (90%). All HO isoforms are highly conserved among species in evolution. HO is expressed in virtually all life forms; in prokaryotic bacteria as well as in fungi, plants, and humans, regulating a wide spectrum of cellular processes (Terry et al., 2002). The homology between rat, mouse, and human is for HO-1 and HO-2 proteins higher than 80% and 90%, respectively. Under normal physiological conditions, most cells express low or undetectable levels of HO-1 protein, whereas HO-2 proteins are constitutively expressed. HO-3 protein expression awaits further characterization. HO-2 transcription is only up-regulated by few agents, such as opiates and adrenal glucocorticoids (Li and David Clark, 2000; Liu et al., 2000). HO-1 gene expression is highly inducible by more diverse stimuli than any other enzyme described to date (Maines, 1997) and involves a multitude of signaling pathways (Table 2) (Immenschuh and Ramadori, 2000). HO-1 expression is mainly regulated at the transcriptional level. View this table: [in this window] [in a new window] TABLE 2 Selection of different inducers of HO-1 gene expression " provenance.
- _4 value " CO had no known physiological function until Marks and coworkers proposed that CO may play a role similar to nitric oxide (NO) in signal transduction (Marks et al., 1991). During the last decade, NO research has taken a prominent position into the pathogenesis of virtually all diseases. NO signaling prevents hypertension, ameliorates inflammation, and functions as an important messenger molecule (Ignarro, 1996). However, NO has not been able to fulfill the high expectations (Lane, 1998). The efficacy is hampered by the fact that NO is a reactive nitrogen species (RNS). Under oxidative conditions, NO reacts with other ROS resulting in the formation of the highly reactive ONOO- (peroxynitrite) (Wolin et al., 1998). Peroxynitrite does not prevent or ameliorate disease states like NO but, in contrast, exacerbates oxidative and inflammatory stress. CO, in contrast to NO, does not contain free electrons and is therefore relatively inert. Moreover, this simple molecule shares the ability of NO to activate the heme protein guanylyl cyclase by binding to its active site, the heme molecule, resulting in enhanced conversion of guanosine triphosphate (GTP) to guanosine 3,5-cyclic monophosphate (cGMP) and subsequently vasodilation" provenance.
- _2 value "The intracellular Ca2+ signal is the primary determinant of smooth muscle contraction [1, 2]. The elevation of cytosolic Ca2+ level induces phosphorylation of the 20 kDa regulatory myosin light chain (MLC20), which in turn activates myosin ATPase activity, and thereby induces smooth muscle contraction." provenance.
- _4 value "BAG-1 overexpression completely protected breast cancer cells from apoptosis and long-term growth inhibition induced by heat shock" provenance.
- _4 value "BAG-1-mediated resistance to stress-induced growth inhibition" provenance.
- _4 value "BAG-1S overexpression prevented induction of apoptosis after heat shock." provenance.
- _3 value "Furthermore, resistin upregulates adhesion molecules and chemokines and downregulates TRAF-3, an inhibitor of CD40 ligand signaling" provenance.
- _5 value "In comparison with the ubiquitously expressed bHLH protein E47, HEN1 is a very modest transcriptional activator and titration experiments indicate that HEN1, like TAL1, represses E47 mediated transcriptional activation." provenance.
- _7 value "In contrast to our prior finding with native TRL, LPL/LDL(-) did not preferentially activate any one PPAR isoform" provenance.
- _5 value "Also, an inactivating mutation of that residue severely impairs RelA transcriptional activity, blocks its anti-apoptotic function and abrogates the interaction of RelA with the co-activator CBP as well as its recruitment, and that of RNA polymerase II (Pol II) with the interleukin-6 (IL-6) promoter." provenance.
- _3 value "These data indicate that pathophysiological levels of Hcy can alter human monocyte function by upregulating MCP-1 and IL-8 expression and secretion via enhanced formation of intracellular ROS" provenance.
- _5 value "We present evidence that ellipticine can restore the transactivation function of several transfected p53 mutants (175 H, 248W, 249S, 273 H, 281G), resulting in the induction of p53-responsive genes (p21(WAF1),MDM2) and activation of a p53-responsive luciferase reporter. Ellipticine also activates mutant p53 function in tumor cells expressing endogenous 194F, 233L, 241F, and 273C mutants. " provenance.
- _4 value "Here, we show that both proapoptotic Bcl-2 family members Bak and Bax were activated by IFNalpha" provenance.
- _3 value "in vivo administration of tumor necrosis factor-alpha (1,000 units), interleukin-1beta (1,000 units), and interferon-gamma (2,000 units) into the rat pancreas through a bile duct cannula leads to the formation of lipid-derived free radicals in this tissue." provenance.
- _3 value "Glucose stimulation of TSP1 protein expression and TGF-beta bioactivity were also downregulated. TGF-beta-dependent fibronectin and type IV collagen expression under high glucose conditions were significantly reduced upon catalytic domain expression in transfected RMCs." provenance.