Biomedical subjects

David Piquemal

Publications and source records attributed to David Piquemal.

At least 19 recordsLinked to original sources

PubMed2007

Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity.

Disease relapse sometimes occurs after acute promyelocytic leukemia (APL) therapy with all-trans retinoic acid (ATRA). Among the diagnostic parameters predicting relapse, heterogeneity in the in vitro differentiation rate of blasts is an independent factor. To identify biologic networks involved in resistance, we conducted pharmacogenomic studies in APL blasts displaying distinct ATRA sensitivities. Although the expression profiles of genes invested in differentiation were similarly modulated in low- and high-sensitive blasts, low-sensitive cells showed higher levels of transcription of ATRA-target genes, transcriptional regulators, chromatin remodelers, and transcription factors. In opposition, only high-sensitive blasts expressed the CYP26A1 gene, encoding the p450 cytochrome which is known to be involved in retinoic acid catabolism. In NB4 cells, ATRA treatment activates a novel signaling pathway, whereby interleukin-8 stimulates the expression of the homeobox transcription factor HOXA10v2, an effective enhancer of CYP26A1 transcription. These data were corroborated in primary APL cells, as maturation levels correlated with CYP26A1 expression. Treatment with a retinoic acid metabolism blocking agent (RAMBA) results in high-nucleoplasmic concentrations of retinoid and growth of NB4-resistant subclones. Hence, for APL blasts associated with poor prognosis, the low CYP26A1 expression may explain high risk of resistance installation, by increased retinoid pressure. Pharmacogenomic profiles of genes involved in retinoid acid metabolism may help to optimize anticancer therapies, including retinoids.

Cell Proliferation↗

PubMed2006

The tumor metastasis suppressor gene Drg-1 down-regulates the expression of activating transcription factor 3 in prostate cancer.

The tumor metastasis suppressor gene Drg-1 has been shown to suppress metastasis without affecting tumorigenicity in immunodeficient mouse models of prostate and colon cancer. Expression of Drg-1 has also been found to have a significant inverse correlation with metastasis or invasiveness in various types of human cancer. However, how Drg-1 exerts its metastasis suppressor function remains unknown. In the present study, to elucidate the mechanism of action of the Drg-1 gene, we did a microarray analysis and found that induction of Drg-1 significantly inhibited the expression of activating transcription factor (ATF) 3, a member of the ATF/cyclic AMP-responsive element binding protein family of transcription factors. We also showed that Drg-1 attenuated the endogenous level of ATF3 mRNA and protein in prostate cancer cells, whereas Drg-1 small interfering RNA up-regulated the ATF3 expression. Furthermore, Drg-1 suppressed the promoter activity of the ATF3 gene, indicating that Drg-1 regulates ATF3 expression at the transcriptional level. Our immunohistochemical analysis on prostate cancer specimens revealed that nuclear expression of ATF3 was inversely correlated to Drg-1 expression and positively correlated to metastases. Consistently, we have found that ATF3 overexpression promoted invasiveness of prostate tumor cells in vitro, whereas Drg-1 suppressed the invasive ability of these cells. More importantly, overexpression of ATF3 in prostate cancer cells significantly enhanced spontaneous lung metastasis of these cells without affecting primary tumorigenicity in a severe combined immunodeficient mouse model. Taken together, our results strongly suggest that Drg-1 suppresses metastasis of prostate tumor cells, at least in part, by inhibiting the invasive ability of the cells via down-regulation of the expression of the ATF3 gene.

Activating Transcription Factor 3↗

PubMed2006

PenBase, the shrimp antimicrobial peptide penaeidin database: sequence-based classification and recommended nomenclature.

Antimicrobial peptides play a major role in innate immunity. The penaeidins, initially characterized from the shrimp Litopenaeus vannamei, are a family of antimicrobial peptides that appear to be expressed in all penaeid shrimps. As of recent, a large number of penaeid nucleotide sequences have been identified from a variety of penaeid shrimp species and these sequences currently reside in several databases under unique identifiers with no nomenclatural continuity. To facilitate research in this field and avoid potential confusion due to a diverse number of nomenclatural designations, we have made a systematic effort to collect, analyse, and classify all the penaeidin sequences available in every database. We have identified a common penaeidin signature and subsequently established a classification based on amino acid sequences. In order to clarify the naming process, we have introduced a 'penaeidin nomenclature' that can be applied to all extant and future penaeidins. A specialized database, PenBase, which is freely available at , has been developed for the penaeidin family of antimicrobial peptides, to provide comprehensive information about their properties, diversity and nomenclature.

Amino Acid Sequence↗

PubMed2006

Gene profiling during development and after a peripheral nerve traumatism reveals genes specifically induced by injury in dorsal root ganglia.

In order to shed light on transcriptional networks involved in adult peripheral nerve repair program, we propose for the first time an organization of the transcriptional dynamics of the mouse dorsal root ganglia (DRG) following a sciatic nerve lesion. This was done by a non-hierarchical bioinformatical clustering of four Serial Analysis of Gene Expression libraries performed on DRG at embryonic day E13, neonatal day P0, adult and adult 3 days post-sciatic nerve section. Grouping genes according to their expression profiles shows that a combination of down-regulation of genes expressed at the adult stages, re-expression of embryonic genes and induction of a set of de novo genes takes place in injured neurons. Focusing on this latter event highlights Ddit3, Timm8b and Oazin as potential new injury-induced molecular actors involved in a stress response pathway. Their association with the traumatic state was confirmed by real-time PCR and in situ hybridization investigations. Clustering analysis allows us to distinguish developmental re-programming events from nerve-injury-induced processes and thus provides a basis for molecular understanding of transcriptional alterations taking place in the DRG after a sciatic nerve lesion.

Animals↗

PubMed2006

Bovine transcriptome analysis by SAGE technology during an experimental Trypanosoma congolense infection.

In central and sub-Saharan Africa, trypanosomosis is a tsetse fly-transmitted disease, which is considered as the most important impediment to livestock production in the region. However, several indigenous West African taurine breeds (Bos taurus) present remarkable tolerance to the infection. This genetic capability, named trypanotolerance, results from numerous biological mechanisms most probably under multigenic dependences, among which are control of the trypanosome infection by limitation of parasitemia and control of severe anemia due to the pathogenic effects. Today, some postgenomic biotechnologies, such as transcriptome analyses, allow characterization of the full expressed genes involved in the majority of animal diseases under genetic control. One of them is serial analysis of gene expression (SAGE) technology, which consists of the construction of mRNA transcript libraries for qualitative and quantitative analysis of the entire genes expressed or inactivated at a particular step of cellular activation. We developed four different mRNA transcript libraries from white blood cells on a N'Dama trypanotolerant animal during an experimental Trypanosoma congolense (T. congolense) infection: one before experimental infection (ND0), one at the parasitemia peak (NDm), one at the minimal packed cell volume (NDa), and the last one at the end of the experiment after normalization (NDf). Bioinformatic comparisons in bovine genomic databases allowed us to obtain more than 75,000 sequences, among which are several known genes, some others are already described as expressed sequence tags (ESTs), and the last are completely new, but probably functional in trypanotolerance. The knowledge of all identified named or unnamed genes involved in trypanotolerance characteristics will allow us to use them in a field marker-assisted selections strategy and in microarrays prediction sets for bovine trypanotolerance.

Animals↗

PubMed2005

Identification of differentially expressed genes between fetal and adult mouse kidney: candidate gene in kidney development.

BACKGROUND: The kidney development involves a wide variety of developmental processes requiring a lot of genes expressed in a sequential manner. The aim of the present study is to identify new genes involved in these processes. METHODS: To obtain a view of the mouse embryonic kidney transcriptome we used the SADE method, which allows large-scale quantitative gene expression measurements. RESULTS: 7,689 tags were sequenced from our library. Among the 4,507 unique transcripts yielded, 64% correspond to known genes, 22% ESTs, 12% unidentified genes. 472 genes were differentially expressed as compared to published adult kidney library. Among these, we identified several candidate genes and focused on a particular one: thymosin beta4 (Tbeta4), an actin-sequestering protein more highly expressed in fetal kidney. First we studied the in vivo expression patterns of Tbeta4 transcript during kidney development. Tbeta4 increases throughout the kidney development and remains high during active nephrogenesis. Moreover, the spatial distribution of Tbeta4 mRNA was analysed and reveals that during active nephrogenesis (i.e., 18 dpc) Tbeta4 is localised in differentiating glomeruli. In adult kidney, Tbeta4 remains expressed in podocytes and collecting ducts. CONCLUSION: Our results provide the first demonstration of Tbeta4 production in vivo by embryonic kidney and further show that Tbeta4 is implicated in kidney organogenesis.

Aging↗

PubMed2005

Efficiency and limits of the Serial Analysis of Gene Expression (SAGE) method: discussions based on first results in bovine trypanotolerance.

Post genomic biotechnologies, such as transcriptome analysis, are now efficient enough to characterize the full complement of genes involved in the expression of specific biological functions. One of them is the Serial Analysis of Gene Expression (SAGE) technique. SAGE involves the construction of transcript libraries for a quantitative analysis of the entire set of genes expressed or inactivated at particular stages of cellular activation. Bioinformatic comparisons in hosts and pathogens genomic databases allow the identification of several up- and down-regulated genes, ESTs and unknown transcripts directly involved in the host-pathogen immunological interaction mechanisms. Based on the first results obtained during an experimental Trypanosoma congolense infection in trypanotolerant cattle, the efficiency and limits of such a technique, from the data acquisition level to the data analysis level, is discussed in this analysis.

Animals↗

PubMed2004

Mining SAGE data allows large-scale, sensitive screening of antisense transcript expression.

As a growing number of complementary transcripts, susceptible to exert various regulatory functions, are being found in eukaryotes, high throughput analytical methods are needed to investigate their expression in multiple biological samples. Serial Analysis of Gene Expression (SAGE), based on the enumeration of directionally reliable short cDNA sequences (tags), is capable of revealing antisense transcripts. We initially detected them by observing tags that mapped on to the reverse complement of known mRNAs. The presence of such tags in individual SAGE libraries suggested that SAGE datasets contain latent information on antisense transcripts. We raised a collection of virtual tags for mining these data. Tag pairs were assembled by searching for complementarities between 24-nt long sequences centered on the potential SAGE-anchoring sites of well-annotated human expressed sequences. An analysis of their presence in a large collection of published SAGE libraries revealed transcripts expressed at high levels from both strands of two adjacent, oppositely oriented, transcription units. In other cases, the respective transcripts of such cis-oriented genes displayed a mutually exclusive expression pattern or were co-expressed in a small number of libraries. Other tag pairs revealed overlapping transcripts of trans-encoded unique genes. Finally, we isolated a group of tags shared by multiple transcripts. Most of them mapped on to retroelements, essentially represented in humans by Alu sequences inserted in opposite orientations in the 3'UTR of otherwise different mRNAs. Registering these tags in separate files makes possible computational searches focused on unique sense-antisense pairs. The method developed in the present work shows that SAGE datasets constitute a major resource of rapidly investigating with high sensitivity the expression of antisense transcripts, so that a single tag may be detected in one library when screening a large number of biological samples.

Computational Biology↗

PubMed2004

PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer.

PTEN (phosphatase and tensin homologue deleted on chromosome 10) has been shown to be inactivated in a wide variety of cancers, and the role of this gene as a tumor suppressor has been well established. On the other hand, results of recent animal studies as well as clinical evidence indicate that PTEN is also involved in tumor metastasis suppression. Although PTEN is known to play a key role in controlling cell growth and apoptosis, how PTEN exerts the metastasis suppressor function remains largely unknown. Recently, a microarray analysis identified the Drg-1 gene (differentiation related gene 1) as one of the potential targets of PTEN. The Drg-1 gene has been shown to suppress tumor metastasis in animal models of prostate and colon cancer, and the expression of this gene is significantly reduced with advancement of prostate and breast cancers in clinical setting. In this study, we explored the possibility that PTEN controls tumor metastasis by regulating the expression of the Drg-1 gene. Our results indicate that overexpression of PTEN significantly augments the endogenous expression of Drg-1 protein, whereas inhibition of PTEN by small interfering RNA decreases Drg-1 in a dose- and time-dependent manner. We also found that the control of the Drg-1 gene by PTEN seems to be at the transcriptional level, and that a phospho-Akt inhibitor restores the Drg-1 expression, indicating that PTEN controls Drg-1 by an Akt-dependent pathway. Consistent with these results, our immunohistochemical analysis revealed that PTEN expression correlates significantly with Drg-1 in both prostate and breast cancer cases. Furthermore, combination of the two markers, PTEN and Drg-1, emerged as a significantly better predictor of prostate and breast cancer patient survival than either marker alone.

Breast Neoplasms↗

PubMed2004

Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression.

The differentiation-related gene-1 (Drg-1) was first identified as a gene strongly upregulated by induction of differentiation in colon carcinoma cells in vitro, and later the same gene was shown to suppress tumorigenicity of human bladder cancer cells in vivo. On the other hand, we and others have demonstrated that the Drg-1 gene suppresses prostate and colon cancer metastases in mouse models. In the context of such potential organ-specific differential function of the Drg-1 gene, the present study was designed to clarify the expression status, regulation and function of Drg-1 in the case of human breast cancer. We found that the expression of the Drg-1 protein was significantly reduced in breast tumor cells, particularly in patients with lymph node or bone metastasis as compared to those with localized breast cancer. Drg-1 expression also exhibited significant inverse correlation with the disease-free survival rate of patients and emerged as an independent prognostic factor. The downregulation of the Drg-1 gene appeared to be largely at the RNA level, and the DNA methylation inhibitor, 5-Azacytidine, significantly elevated the Drg-1 gene expression in various breast tumor cell lines. Furthermore, we found that overexpression of the Drg-1 gene suppresses the invasiveness of breast cancer cells in vitro, and this suppression was also achieved by treatment of cells with 5-Azacytidine. Together, our results strongly suggest functional involvement of the Drg-1 gene in suppressing the metastatic advancement of human breast cancer.

Breast Neoplasms↗

PubMed2004

The Arabidopsis root transcriptome by serial analysis of gene expression. Gene identification using the genome sequence.

Large-scale identification of genes expressed in roots of the model plant Arabidopsis was performed by serial analysis of gene expression (SAGE), on a total of 144,083 sequenced tags, representing at least 15,964 different mRNAs. For tag to gene assignment, we developed a computational approach based on 26,620 genes annotated from the complete sequence of the genome. The procedure selected warrants the identification of the genes corresponding to the majority of the tags found experimentally, with a high level of reliability, and provides a reference database for SAGE studies in Arabidopsis. This new resource allowed us to characterize the expression of more than 3,000 genes, for which there is no expressed sequence tag (EST) or cDNA in the databases. Moreover, 85% of the tags were specific for one gene. To illustrate this advantage of SAGE for functional genomics, we show that our data allow an unambiguous analysis of most of the individual genes belonging to 12 different ion transporter multigene families. These results indicate that, compared with EST-based tag to gene assignment, the use of the annotated genome sequence greatly improves gene identification in SAGE studies. However, more than 6,000 different tags remained with no gene match, suggesting that a significant proportion of transcripts present in the roots originate from yet unknown or wrongly annotated genes. The root transcriptome characterized in this study markedly differs from those obtained in other organs, and provides a unique resource for investigating the functional specificities of the root system. As an example of the use of SAGE for transcript profiling in Arabidopsis, we report here the identification of 270 genes differentially expressed between roots of plants grown either with NO3- or NH4NO3 as N source.

Arabidopsis↗

PubMed2004

Use of the Serial Analysis of Gene Expression (SAGE) method in veterinary research: A concrete application in the study of the bovine trypanotolerance genetic control.

New postgenomic biotechnologies, such as transcriptome analyses, are now able to characterize the full complement of genes involved in the expression of specific biological functions. One of these is the Serial Analysis of Gene Expression (SAGE) technique, which consists of the construction of transcripts libraries for a quantitative analysis of the entire gene(s) expressed or inactivated at a particular step of cellular activation. Bioinformatic comparisons in the bovine genomic databases allow the identification of several up- and downregulated genes, expressed sequence tags, and unknown functional genes directly involved in the genetic control of the studied biological mechanism. We present and discuss the preliminary results in comparing the expressed genes in two total mRNA transcripts libraries obtained during an experimental Trypanosoma congolense infection in one trypanotolerant N'Dama animal cow. Knowing all the functional genes involved in the trypanotolerance control will permit validation of some results obtained with the quantitative trait locus approach, to set up specific microarrays sets for further metabolic and pharmacological studies, and to design field marker-assisted selection by introgression programs.

Animals↗

PubMed2004

Analysis of human reticulocyte genes reveals altered erythropoiesis: potential use to detect recombinant human erythropoietin doping.

BACKGROUND AND OBJECTIVES: Enhancement of oxygen delivery to tissues is associated with improved sporting performance. One way of enhancing oxygen delivery is to take recombinant human erythropoietin (rHuEpo), which is an unethical and potentially dangerous practice. However, detection of the use of rHuEpo remains difficult in situations such as: i) several days after the end of treatment ii) when a treatment with low doses is conducted iii) if the rHuEpo effect is increased by other substances. In an attempt to detect rHuEpo abuse, we selected erythroid gene markers from a SAGE library and analyzed the effects of rHuEpo administration on expression of the HBB, FTL and OAZ genes. DESIGN AND METHODS: Ten athletes were assigned to the rHuEpo or placebo group. The rHuEpo group received subcutaneous injections of rHuEpo (50 UI/kg three times a week, 4 weeks; 20 UI/kg three times a week, 2 weeks). HBB, FTL and OAZ gene profiles were monitored by real time-polymerase chain reaction (PCR) quantification during and for 3 weeks after drug administration. RESULTS: The global analysis of these targeted genes detected in whole blood samples showed a characteristic profile of subjects misusing rHuEpo with a increase above the threshold levels. The individual analysis of OAZ mRNA seemed indicative of rHuEpo treatment. INTERPRETATION AND CONCLUSIONS: The performance-enhancing effect of rHuEpo treatment is greater than the duration of hematologic changes associated with rHuEpo misuse. Although direct electrophoretic methods to detect rHuEpo have been developed, recombinant isoforms of rHuEpo are not detectable some days after the last subcutaneous injection. To overcome these limitations indirect OFF models have been developed. Our data suggest that, in the near future, it will be possible to consolidate results achievable with the OFF models by analyzing selected erythroid gene markers as a supplement to indirect methods.

Adolescent↗

PubMed2004

Analysis of remnant reticulocyte mRNA reveals new genes and antisense transcripts expressed in the human erythroid lineage.

BACKGROUND AND OBJECTIVES: We studied the gene expression profile of human purified reticulocytes to provide a transcriptional basis for the study of erythroid biology, differentiation and hematologic disorders. DESIGN AND METHODS: We screened highly purified blood reticulocytes from ten healthy adult volunteers. We chose a modified protocol of serial analysis of gene expression (SAGE), the serial analysis of downsized extracts (SADE). RESULTS: Data analysis revealed that 64% of gene signatures (tags) matched with known genes; mainly hemoglobin. In addition to the abundant globin mRNA, SAGE analysis identified previously described genes and new transcripts. In reticulocytes, which are poor in mRNA, we also identified 9% of EST and 27% of tags that did not match with any known genes. Mining our data, 70% of the unknown tags and 39% of tags identifying EST were found to be specific to the reticulocyte. We demonstrated the presence of a mRNA that matched with the reverse sequence of the hemoglobin b (HBB) transcript. INTERPRETATION AND CONCLUSIONS: This is the first description of an antisense transcript of the human HBB gene suggesting regulation by way of sense-antisense pairing. The well-characterized genes found in the SAGE library were genes specific to the blood cell lineage, housekeeping genes and, interestingly, genes not previously described in the reticulocyte. Furthermore the study provides markers of the erythroid lineage regulated during the differentiation process as observed in in vitro experiments.

Adult↗

PubMed2003

Serial analysis of gene expression (SAGE) in bovine trypanotolerance: preliminary results.

In Africa, trypanosomosis is a tsetse-transmitted disease which represents the most important constraint to livestock production. Several indigenous West African taurine Bos taurus) breeds, such as the Longhorn (N'Dama) cattle are well known to control trypanosome infections. This genetic ability named "trypanotolerance" results from various biological mechanisms under multigenic control. The methodologies used so far have not succeeded in identifying the complete pool of genes involved in trypanotolerance. New post genomic biotechnologies such as transcriptome analyses are efficient in characterising the pool of genes involved in the expression of specific biological functions. We used the serial analysis of gene expression (SAGE) technique to construct, from Peripheral Blood Mononuclear Cells of an N'Dama cow, 2 total mRNA transcript libraries, at day 0 of a Trypanosoma congolense experimental infection and at day 10 post-infection, corresponding to the peak of parasitaemia. Bioinformatic comparisons in the bovine genomic databases allowed the identification of 187 up- and down- regulated genes, EST and unknown functional genes. Identification of the genes involved in trypanotolerance will allow to set up specific microarray sets for further metabolic and pharmacological studies and to design field marker-assisted selection by introgression programmes.

Africa South of the Sahara↗

PubMed2002

Transcriptome analysis of monocytic leukemia cell differentiation.

The human leukemia cell line U937 is a well-established model for studying monocytic cell differentiation. We used a modified protocol (SADE) of serial analysis of gene expression (SAGE) and developed a SADE linker-anchored PCR assay to investigate the pattern of expression of known genes and to identify new transcripts in proliferating cells and during cell growth arrest and differentiation. We implemented new informatic tools to compare expression profiles before and after exposure of cells to differentiation inducers. From the analysis of 47,388 tags, we identified 13,806 distinct transcripts, 265 of which showed significant variations (P<0.01). Among 1219 well-identified genes, major changes concerned transcription and translation components, cytoskeleton, and macrophage-specific genes. Nearly half of the tags, some of them expressed at high levels, matched partially characterized genes or ESTs, or revealed yet-unknown transcripts, providing a wealth of new candidate genes that may reveal novel aspects of terminal monocytic differentiation.

Cell Differentiation↗

PubMed2002

White spot syndrome virus and infectious hypodermal and hematopoietic necrosis virus simultaneous diagnosis by miniarray system with colorimetry detection.

Highly sensitive and specific diagnostic tools are essential for monitoring the health status of farmed species. After the development of genomic probe diagnostic systems in the 1990s, followed by PCR-based systems, a miniarray method has been developed allowing one-step multiple detection. The miniarray method was developed to enable the accessibility of powerful array technology. To use this system, hybridisation and washing process were modified, resulting into a significant increase in the test's rapidity and sensitivity. With miniarray technology, hybridisation time is reduced to 20 min, whereas other methods require a longer hybridisation time. Hybridisation of the PCR product on a nylon membrane and revelation of the hybrids by an antibody increase considerably the ability of pathogen's detection. A first application is developed for the diagnosis of two specific viruses which are, by their geographical range and their impact on the production, very important in shrimp pathology, namely, the White Spot Syndrome Virus (WSSV) and the Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV).

Animals↗

PubMed2002

The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia.

Hypoxia causes the accumulation of the transcription factor hypoxia-inducible factor 1 (HIF-1), culminating in the expression of hypoxia-inducible genes such as those for vascular endothelial growth factor (VEGF) and NDRG-1/Cap43. Previously, we have demonstrated that intracellular calcium (Ca(2+)) is required for the expression of hypoxia-inducible genes. Here we found that, unlike with hypoxia or hypoxia-mimicking conditions, the elevation of intracellular Ca(2+) neither induced the HIF-1alpha protein nor stimulated HIF-1-dependent transcription. Furthermore, the elevation of intracellular Ca(2+) induced NDRG-1/Cap43 mRNA in HIF-1alpha-deficient cells. It also increased levels of c-Jun protein, causing its phosphorylation. The protein kinase inhibitor K252a abolished c-Jun induction and activator protein 1 (AP-1)-dependent reporter expression caused by Ca(2+) ionophore or hypoxia. K252a also significantly decreased hypoxia-induced VEGF and NDRG-1/Cap43 gene expression in both human and mouse cells. Using a set of deletion VEGF-Luc promoter constructs, we found that both HIF-1 and two AP-1 sites contribute to hypoxia-mediated induction of transcription. In contrast, only AP-1 sites contributed to Ca(2+)-mediated VEGF-Luc induction. A dominant-negative AP-1 prevented Ca(2+)-dependent transcription and partially impaired hypoxia-mediated transcription. In addition, dominant-negative AP-1 diminished the expression of the NDRG-1/Cap43 gene following hypoxia. We conclude that during hypoxia, an increase in intracellular Ca(2+) activates a HIF-1-independent signaling pathway that involves AP-1-dependent transcription. Cooperation between the HIF-1 and AP-1 pathways allows fine regulation of gene expression during hypoxia.

Animals↗