Fanja Rabenoelina - Academia.edu (original) (raw)

Papers by Fanja Rabenoelina

Diabetes, 2013

Although it has long been established that the extracellular matrix acts as a mechanical support,... more Although it has long been established that the extracellular matrix acts as a mechanical support, its degradation products, which mainly accumulate during aging, have also been demonstrated to play an important role in cell physiology and the development of cardiovascular and metabolic diseases. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels on the b-chain of the IR and reduction of IR signaling. In conclusion, this is the first study to demonstrate that EDPs, which mainly accumulate with aging, may be involved in the insidious development of IRES. Diabetes 62:3807-3816, 2013

Functional Plant Biology, 2011

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Environ Toxicol Chem, 2007

The steroid hormones estrone (E 1 ), 17␤-estradiol (E 2 ), estriol (E 3 ), 17␣-ethinylestradiol (... more The steroid hormones estrone (E 1 ), 17␤-estradiol (E 2 ), estriol (E 3 ), 17␣-ethinylestradiol (EE 2 ), and their conjugated forms were surveyed throughout an advanced sewage treatment plant (STP). The estrogen concentrations in water and sludge samples, collected in October 2004 and April 2005, were determined by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. Simultaneously, the estrogenic activity was quantified using estrogen-responsive reporter cell lines (MELN) to investigate the behavior of overall estrogenic compounds. The estrogen concentrations in the inlet ranged from 200 to 500 ng/L, with the contribution of conjugated forms being higher than 50%. The major estrogens in influent were E 1 and E 3 . The estrogenic activity was between 25 and 130 ng/L of E 2 equivalents (EEQs). Estrogen concentrations and estrogenicity measured in the inlet and in primary treated sewage were similar, showing a weak impact of primary treatment on hormone removal. In contrast, both estrogen concentration and estrogenicity decreased during biological treatment, with high removal efficiencies (Ͼ90%). Estrone, E 2 , and EE 2 persisted in the treated water below 10 ng/L, whereas the estrogenicity was lower than 5 ng/L of EEQs. Estrogen mass flux in the effluent and sludge represented less than 2 and 4%, respectively, of the inlet. Consequently, the fraction of estrogens sorbed into the sludge was very small, and biodegradation was the main vehicle for estrogen elimination. This dual approach, comparing chemical and biological analysis, allowed us to confirm that most of the estrogenic activity occurring in this STP, which receives mainly domestic sewage, resulted from sex hormones.

Frontiers in Plant Science, 2015

Bioresource technology, 2014

Designing more efficient mixtures of enzymes is necessary to produce molecules of interest from b... more Designing more efficient mixtures of enzymes is necessary to produce molecules of interest from biomass lignocellulosic fractionation. The present study aims to investigate the strategies used by the thermophilic and hemicellulolytic bacterium Thermobacillus xylanilyticus to fractionate wheat bran and wheat straw during its growth. Results demonstrated ratios and levels of hemicellulases produced varied during growth on both biomasses. Xylanase activity was mainly produced during stationary stages of growth whereas esterase and arabinosidase activities were detected earlier. This enzymatic profile is correlated with the expression pattern of genes encoding four hemicellulases (two xylanases, one arabinosidase and one esterase) produced by T. xylanilyticus during growth. Based on identification of the bacterial strategy, the synergistic efficiency of the four hemicellulases during the hydrolysis of both substrates was evaluated. The four hemicellulases worked together with high degre...

Phytopathology, 2010

Plant infection by pathogens generates various forms of symptoms. Most of them have been describe... more Plant infection by pathogens generates various forms of symptoms. Most of them have been described as soon as they become visible, whereas preceding, discrete signs during incubation are poorly or not understood. In Vitis vinifera, esca-related pathogenic fungi inhabit living trunk wood and induce the so-called apoplexy, a sudden wilting of leaves within a few days. To further understand the apoplexy expression, the period preceding symptom appearance was investigated by following physiological and molecular markers associated with photosynthetic mechanisms and stress responses. Within the week preceding symptoms, drastic physiological alterations of photosynthesis were registered in pre-apoplectic vines, as revealed by a decrease in gas exchange, changes in chlorophyll fluorescence, and repression of photosynthesis-related genes. In the meantime, expression of defense-related genes was induced and amplified during symptom expression. Water-stress-related genes were specifically inv...

Methodologies and Results in Grapevine Research, 2010

... Samples were ground in liquid nitrogen to a fine powder with a laboratory ball mill with inox... more ... Samples were ground in liquid nitrogen to a fine powder with a laboratory ball mill with inox grinding balls of 30 mm diameter (Prolabo ... One hundred and fifty ng of total RNA were reverse-transcribed by using the Verso SYBR Green 2-Step QRT-PCR Rox kit (ThermoElectron, ...

Pregnane X receptor (hPXR, NR1I2) is activated by various chemically unrelated compounds, includi... more Pregnane X receptor (hPXR, NR1I2) is activated by various chemically unrelated compounds, including environmental pollutants and drugs. We proceeded here to in vitro screening of 28 pesticides with a new reporter system that detects hPXR activators. The cell line was obtained by a two-step stable transfection of cervical cancer HeLa cells. The first transfected cell line, HG 5 LN, contained an integrated luciferase reporter gene under the control of a GAL4 yeast transcription factor binding site. The second cell line, HGPXR, was derived from HG 5 LN and stably expressed hPXR ligand binding domain (LBD) fused to GAL4 DNA binding domain (DBD). The HG 5 LN cells were used as a control to detect nonspecific activities. Pesticides from various chemical classes were demonstrated, for the first time, to be hPXR activators: i) herbicides: pretilachlor, metolachlor and alachlor chloracetanilides, oxadiazon oxyconazole, and isoproturon urea; ii) fungicides: bupirimate and fenarimol pyrimidines, propiconazole, fenbuconazole, prochloraz conazoles and imazalil triazole; and iii) insecticides: toxaphene organochlorine, permethrin pyrethroid, fipronil pyrazole, and diflubenzuron urea. Pretilachlor, metolachlor, bupirimate and oxadiazon had an affinity for hPXR equal to or greater than the positive control rifampicin.

Toxicological Sciences, 2006

Pregnane X receptor (PXR, NR1I2) is activated by various chemically unrelated compounds, includin... more Pregnane X receptor (PXR, NR1I2) is activated by various chemically unrelated compounds, including environmental pollutants and drugs. We proceeded here to in vitro screening of 28 pesticides with a new reporter system that detects human pregnane X receptor (hPXR) activators. The cell line was obtained by a two-step stable transfection of cervical cancer HeLa cells. The first transfected cell line, HG 5 LN, contained an integrated luciferase reporter gene under the control of a GAL4 yeast transcription factor-binding site. The second cell line HGPXR was derived from HG 5 LN and stably expressed hPXR ligand-binding domain fused to GAL4 DNA-binding domain (DBD). The HG 5 LN cells were used as a control to detect nonspecific activities. Pesticides from various chemical classes were demonstrated, for the first time, to be hPXR activators: (1) herbicides: pretilachlor, metolachlor, and alachlor chloracetanilides, oxadiazon oxiconazole, and isoproturon urea; (2) fungicides: bupirimate and fenarimol pyrimidines, propiconazole, fenbuconazole, prochloraz conazoles, and imazalil triazole; and (3) insecticides: toxaphene organochlorine, permethrin pyrethroid, fipronil pyrazole, and diflubenzuron urea. Pretilachlor, metolachlor, bupirimate, and oxadiazon had an affinity for hPXR equal to or greater than the positive control rifampicin. Some of the newly identified hPXR activators were also checked for their ability to induce cytochrome P450 3A4 expression in a primary culture of human hepatocytes. HGPXR, with HG 5 LN as a reference, was grafted onto nude mice to assess compound bioavailability through in vivo quantification of hPXR activation. Altogether, our data indicate that HGPXR cells are an efficient tool for identifying hPXR ligands and establishing pesticides as hPXR activators.

The Journal of Steroid Biochemistry and Molecular Biology, 2009

This work was undertaken i) to study deeply the estrogen, androgen and progestative activity of t... more This work was undertaken i) to study deeply the estrogen, androgen and progestative activity of tibolone and its metabolites ii) to determine whether tibolone and its metabolites present glucocorticoid or mineralocorticoid activity. For this purpose, we used human cell lines bearing a luciferase gene with a responsive element under the control of human estrogen receptor α (ER α) or estrogen receptor β (ER β) or androgen receptor (AR) or chimeric Gal4 fusion with progesterone receptor (PR), glucocorticoid receptor (GR) or mineralocorticoid receptor (MR). The major tibolone metabolites, the two hydroxymetabolites, bind and activate ER with a preference for ERα. Tibolone and the ∆ 4 -tibolone are agonists for AR and PR and surprisingly 3α -and 3 β-OH-tibolone are antagonists for them. Moreover we showed for the first time that tibolone and its primary metabolites bind to GR and MR and are all antagonists for them. In conclusion, tibolone by these actions on different receptors and by this capacity to transform in different metabolites, has more complex effects than initially supposed.

The Journal of Steroid Biochemistry and Molecular Biology, 2005

Our study focused on aromatase cytochrome P450 (CYP19) expression in ovarian epithelial normal an... more Our study focused on aromatase cytochrome P450 (CYP19) expression in ovarian epithelial normal and cancer cells and tissues. Aromatase mRNA expression was analyzed by real-time PCR in ovarian epithelial cancer cell lines, in human ovarian surface epithelial (HOSE) cell primary cultures, and in ovarian tissue specimens (n=94), including normal ovaries, ovarian cysts and cancers. Aromatase mRNA was found to be expressed in HOSE cells, in BG1, PEO4 and PEO14, but not in SKOV3 and NIH:OVCAR-3 ovarian cancer cell lines. Correlation analysis of aromatase expression was performed according to clinical, histological and biological parameters. Aromatase expression in ovarian tissue specimens was higher in normal ovaries and cysts than in cancers (P<0.0001). Using laser capture microdissection in normal postmenopausal ovaries, aromatase was found to be predominantly expressed in epithelial cells as compared to stromal component. Using immunohistochemistry (IHC), aromatase was also detected in the epithelium component. There was an inverse correlation between aromatase and ERalpha expression in ovarian tissues (P<0.001, r=-0.34). In the cancer group, no significant differences in aromatase expression were observed according to tumor histotype, grade, stage and survival. Aromatase activity was evaluated in ovarian epithelial cancer (OEC) cell lines by the tritiated water assay and the effects of third-generation aromatase inhibitors (AIs) on aromatase activity and growth were studied. Letrozole and exemestane were able to completely inhibit aromatase activity in BG1 and PEO14 cell lines. Interestingly, both AI showed an antiproliferative effect on the estrogen responsive BG1 cell line co-expressing aromatase and ERalpha. Aromatase expression was found in ovarian epithelial normal tissues and in some ovarian epithelial cancer cells and tissues. This finding raises the possibility that some tumors may respond to estrogen and provides a basis for ascertaining an antimitogenic effect of AI in a subgroup of ovarian epithelial cancers.

Plant, Cell & Environment, 2009

Rhamnolipids produced by the bacteria Pseudomonas aeruginosa are known as very efficient biosurfa... more Rhamnolipids produced by the bacteria Pseudomonas aeruginosa are known as very efficient biosurfactant molecules. They are used for a wide range of industrial applications, especially in food, cosmetics and pharmaceutical formulations as well as in bioremediation of pollutants. In this paper, the role of rhamnolipids as novel molecules triggering defence responses and protection against the fungus Botrytis cinerea in grapevine is presented. The effect of rhamnolipids was assessed in grapevine using cell suspension cultures and vitro-plantlets. Ca 2+ influx, mitogenactivated protein kinase activation and reactive oxygen species production form part of early signalling events leading from perception of rhamnolipids to the induction of plant defences that include expression of a wide range of defence genes and a hypersensitive response (HR)-like response. In addition, rhamnolipids potentiated defence responses induced by the chitosan elicitor and by the culture filtrate of B. cinerea. We also demonstrated that rhamnolipids have direct antifungal properties by inhibiting spore germination and mycelium growth of B. cinerea. Ultimately, rhamnolipids efficiently protected grapevine against the fungus.We propose that rhamnolipids are acting as microbeassociated molecular patterns (MAMPs) in grapevine and that the combination of rhamnolipid effects could participate in grapevine protection against grey mould disease.

Molecular Pharmacology, 2003

Mutation of a single amino acid in the ligand-binding domain (LBD) of the human androgen receptor... more Mutation of a single amino acid in the ligand-binding domain (LBD) of the human androgen receptor (hAR) can induce functional abnormalities in androgen binding, stabilization of active conformation, or interaction with coactivators. The Gly708Ala and Gly708Val substitutions are associated with partial and complete androgen insensitivity syndromes, respectively. In this work, we introduced Ala, Val, and aromatic Phe mutations at position 708 on helix H3 of the hAR-LBD and tested the functional and structural consequences on hAR activity in the presence of steroidal or nonsteroidal agonists and antagonists. The residues involved in the specific recognition of these an-This work was supported by the Institut National de la Santé et de la Recherche Médicale, and grant 5205 from the Association pour la Recherche sur le Cancer.

Molecular Pharmacology, 2006

Receptor interacting protein 140 (RIP140) is a negative transcriptional regulator of nuclear horm... more Receptor interacting protein 140 (RIP140) is a negative transcriptional regulator of nuclear hormone receptors that is required for the maintenance of energy homeostasis and ovulation. In this study, we investigated the mechanisms by which RIP140 expression is controlled by estrogens in breast cancer cells. We first analyzed by real time reverse transcription-polymerase chain reaction the regulation of RIP140 mRNA accumulation by estrogen receptor (ER) ligands in MCF-7 cells. We showed that the induction by estradiol (E2) was rapid and did not affect the apparent stability of the mRNA, suggesting a direct transcriptional regulation. To further study the underlying regulatory mechanisms, we then characterized the human RIP140 gene. We identified several noncoding exons with al-

Journal of Experimental Botany, 2013

International Journal of Cancer, 2009

Although it is well established that some protein tyrosine kinases have a prognostic value in bre... more Although it is well established that some protein tyrosine kinases have a prognostic value in breast cancer, the involvement of protein tyrosine phosphatases (PTPs) is poorly substantiated for breast tumours. Three of these enzymes (PTP-gamma, LAR and PTPL1) are already known to be regulated by estrogens or their antagonists in human breast cancer cells. We used a real-time reverse-transcriptase-polymerase-chain-reaction method to test the expression levels of PTP-gamma, LAR and its neuronal isoform, and PTPL1 in a training set of RNA from 59 breast tumours. We sought correlations between levels of these molecular markers, current tumour markers, and survival. We then quantified the expression level of the selected phosphatase in 232 additional samples, resulting in a testing set of 291 breast tumour RNAs from patients with a median follow-up of 6.4 years. The Spearman nonparametric test revealed correlations between PTPL1 expression and differentiation markers. Cox univariate analysis of the overall survival studies demonstrated that PTPL1 is a prognostic factor (risk ratio 0.45), together with the progesterone receptor = (PR) (risk ratio 0.52) and node involvement (risk ratio 1.58). In multivariate analyses, PTPL1 and PR retained their prognostic = = value (risk ratios of 0.48 and 0.55, respectively). This study demonstrates for the first time that PTPL1 expression level is an independent prognostic indicator of favourable outcome for patients with breast cancer. In conjunction with our mechanistic studies, this finding identifies PTPL1 as an important regulatory element of human breast tumour aggressiveness and sensitivity to treatments such as anti-estrogens and anti-aromatase.

International Journal of Cancer, 2002

Resistance to the antiestrogen tamoxifen is the main stumbling block for the success of breast ca... more Resistance to the antiestrogen tamoxifen is the main stumbling block for the success of breast cancer therapy. We focused our study on cellular alterations induced by a prolonged treatment with the active tamoxifen metabolite hydroxytamoxifen (OHT). We show that a prolonged OHT treatment (for up to 7 days) led to a progressive increase in the level of phosphorylated p44/42 mitogen activated kinase (MAP kinase) induced by 10 ؊7 M TPA stimulation, without any significant change in the protein level. This effect was also observed in MCF-7 cells grown first in medium containing dextran-coated charcoal-treated FCS (DCC medium) for 20 days prior to OHT treatment, indicating a specific effect of the antiestrogen and not an effect of estrogen deprivation. It was prevented by cotreatment with estradiol and not observed in the estrogen receptor negative HeLa cell line, suggesting that it was mediated by the estrogen receptor. TPA induced phosphorylation of MEK1/2 was also raised by OHT treatment, without any change in their protein level or Raf-1 and H-Ras levels. When the MCF-7R OHT resistant cell line was grown in antiestrogen containing medium, the level of phosphorylated p44/42 MAP kinase was also high but reversed when the antiestrogen was removed. The 2 other MAP kinase, JNK and P38 pathways were not affected in the same way by OHT treatment. In conclusion, our data reveal that a prolonged OHT treatment, by increasing p44/42 MAPK activity, affects a key step in the growth control of MCF-7 cells, although not sufficiently to overcome the growth inhibitory effect of the drug.

Experimental Cell Research, 2003

Muscle growth results from a set of complex processes including myogenic transcription factor&amp... more Muscle growth results from a set of complex processes including myogenic transcription factor&amp;amp;amp;amp;amp;#39;s expression and activity, cell cycle withdrawal, myoblast fusion in myotubes, and acquisition of an apoptosis-resistant phenotype. Myostatin, a member of the TGFbeta family, described as a strong regulator of myogenesis in vivo Nature 387 (1997), 83; FEBS Lett. 474 (2000), 71 is upregulated during in vitro differentiation Biochem. Biophys. Res. Commun. 280 (2001), 561. To improve characterization of myostatin&amp;amp;amp;amp;amp;#39;s myogenic influence, we stably transfected vectors expressing myostatin and myostatin antisense in C2C12 myoblasts. Here, we found that myostatin inhibits cell proliferation and differentiation. Our results also indicate that myogenin is an important target of myostatin. In addition, overexpressed but not endogenous myostatin decreases MyoD protein levels and induces changes in its phosphorylation pattern. We also established that myostatin overexpression reduces the frequency of G0/G1-arrested cells during differentiation. Conversely, inhibition of myostatin synthesis leads to enhanced cell cycle withdrawal and consequently stimulates myoblast differentiation. We examined the expression patterns of the pRb, E2F1, p53, and p21 proteins involved in cell cycle withdrawal. We found that myostatin overexpression increases p21 and p53 expression, as it does accumulation of hypophosphorylated Rb. Interestingly, myostatin overexpression strongly reduced low-mitogen-induced apoptosis, whereas antisense expression induced contrary changes. In conclusion, these data show the influence of overexpressed myostatin on myoblast proliferation, differentiation, and apoptosis is extended to endogenous myostatin. Though some differences in overexpression or inhibition of endogenous myostatin were observed, it appears that myogenin and p21 are essential targets of this growth factor.