Winter wheat (Triticum aestivum) shows local, induced resistance against the plant-pathogenic fun... more Winter wheat (Triticum aestivum) shows local, induced resistance against the plant-pathogenic fungus Erysiphe graminis f. sp. tritici following exposure to the nonpathogen E. g. f. sp. hordei. The onset of this resistance has been shown to be correlated with the activation of putative defense genes, and cDNA clones representing transcripts of induced genes have been obtained (P. Schweizer, W. Hunziker, and E. Mösinger, Plant Molecular Biology 12:643-654, 1989). We have cloned and sequenced a gene corresponding to one of these cDNAs, WIR5. Sequence analysis indicated that this gene contains three exons and encodes a protein of 229 amino acids. S1 mapping showed that transcripts homologous to this gene are at least 20 times more abundant in leaves infected 14 hr earlier with E. g. f. sp. hordei than in control leaves. Sequence comparison showed that the WIR5 gene product is highly homologous to glutathione-S-transferases (GSTs; EC 25.1.18) of maize. This, together with the fact that the intron positions of both the wheat gene and the maize GSTI gene are conserved, suggests that the cloned pathogen-induced gene, named GstA1, encodes a wheat glutathione-S-transferase.
Wheat (Triticum aestivum) exhibits local acquired resistance to the powdery mildew pathogen Erysi... more Wheat (Triticum aestivum) exhibits local acquired resistance to the powdery mildew pathogen Erysiphe graminis f. sp. tritici. The resistant state can be induced by a preinoculation with the nonhost pathogen E. g.f. sp. hordei, the barley powdery mildew, and is accompanied by the activation of putative defense genes. Here, we report the sequence of a pathogen-induced gene, WIR1a, and a corresponding cDNA, WIR1, that encode novel defense-related proteins of 88 and 85 amino acids, respectively. Analysis of the primary structure of these proteins predicts them to be integral membrane proteins with extracytoplasmic C-terminal domains rich in proline and glycine, through which the proteins possibly interact with the cell wall.
After its identification by Evans and Nason (1953), nitrate reductase (NR) was shown to be a subs... more After its identification by Evans and Nason (1953), nitrate reductase (NR) was shown to be a substrate inducible enzyme by Tang and Wu (1957). In 1960 Hageman and Flesher demonstrated further that both light and N03-were required for the appearance of nitrate reductase activity (Hageman and Flesher 1960). Since that time there have been many reports confirming the initial observations with light and N03-and conflicting reports concerning the repression of the induction of NR by Nl4+ (Beevers and Hageman 1972; Ullrich 1987). Two factors could be important in the appearance of NR activity. The activation of NR, for example, has been elegantly demonstrated in the green alga Chiorelia by Losada et al. (1970) and by Pistorious et al. (1976). A de novo synthesis of the NR protein in response to N03-has been demonstrated by Amy and Garrett (1979) in Neurospora crassa and this phenomenon may also be important in algae and higher plants. Research in higher plants has emphasized de novo synthesis (Remmler and Campbell 1986). However, there have also been several preliminary reports of a reversible activation of NR in higher plants (Aryan and Wallace 1983; Palacian et al. 1974; Somers et al. 1983). An activation/inactivation phenomenon may, for example, be of importance in light/dark transitions (Campbell 1987) or in the response of NR to drought (Aryan and Wallace 1983). The ability to purify NR (Solomonson 1985), and to prepare antibodies to that protein allows us to quantitate the protein either by the ELISA method (Campbell and Remmler 1986) or by SDS-PAGE followed by immunoblotting (Oaks et al. 1988). Thus with an improved system we were able to confirm the early results with light and N03-on the appearance ofNR activity. A 116 kD protein which reacts with polyclonal antibody raised against a pure NR from maize leaves is also present in crude extracts prepared from light-grown but not in dark-grown seedling shoots (Oaks et al. 1988). At this stage of the investigation we can conclude either that this polypeptide is not made in the dark or that it is very unstable in dark-grown seedlings. The induction of the NR protein was apparent in the absence of N03-in the light. The explanation for this unexpected observation turned out to be an induction system in maize that is extremely sensitive to low levels of external N03-. Sufficient levels of N03-are present in sand, vermiculite and Kimpack papers (Oaks et al. 1988). In a hydroponic system,
Current Plant Science and Biotechnology in Agriculture, 1987
Until recently the study of nitrogen fixation genes from Rhizobium has focused either on nif gene... more Until recently the study of nitrogen fixation genes from Rhizobium has focused either on nif genes as they have been defined in Klebsiella pneumoniae (Dixon, 1984), or on fix genes closely linked to nif genes (such as fixABC, Puhler et al., 1984; Ausubel et al., 1985). However we may expect some non nif functions to be important for nitrogen fixation in planta: differentiation of bacteria into bacteroids, bacteroid specific metabolic functions, Rhizobium-dependent nodule maturation, plant dependent regulation of bacteroid functions.
When present in Escherichia coli on the multicopy expression vector pUC19, a Rhizobium meliloti r... more When present in Escherichia coli on the multicopy expression vector pUC19, a Rhizobium meliloti regulatory gene, fixJ, belonging to a two-component regulatory system, activated the expression of two R. meliloti symbiotic genes, nifA and fixK. Primer extension by reverse transcription showed that FixJ stimulates nifA expression in E. coli by activating pnifA.
The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition... more The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac...
Las cianobacterias, las algas y las plantas superiores son capaces de captar la energia luminica ... more Las cianobacterias, las algas y las plantas superiores son capaces de captar la energia luminica para la reduccion fotosintetica de C02 a (CH20) utilizando H20 como reductor. Este proceso se lleva a cabo en el caso de las plantas superiores en organelas especializadas, los cloroplastos, los cuales contienen los pigmentos que absorben la luz distribuidos en vesiculas membranosas (tilacoides). Una vez captada, la energia luminica es covertida en energia electroquimica en la cadena fotosintetica de transporte de eletrones. En este proceso se generan ATP y NADPH, los cuales son utilizados por las enzimas del ciclo de Benson-Calvin (ciclo reductivo de las pentosas fosfato), localizadas en la porcion soluble del cloroplasto (estroma), para la fijacion del C02. Estas enzimas, a excepcion de la fosforribuloquinasa y la ribulosa-1,5-bisfosfato carboxilasa (la proteina mas abundante en la naturaleza) estan distribuidas ampliamente entre los organismos vivos y actuan tanto en la sintesis como ...
Multidrug resistance of mammalian tumor cells is caused by the enhanced expression of P-glycoprot... more Multidrug resistance of mammalian tumor cells is caused by the enhanced expression of P-glycoproteins. These proteins are encoded by mdr genes and mediate the energy-dependent efflux of a variety of lipophilic drugs from cells. To test whether in plants mdr-like genes might be involved in certain cases of cross-resistance to different herbicides, we have cloned and characterized a gene from Arabidopsis thaliana, atpgp1, encoding a putative P-glycoprotein homologue. Like the mammalian P-glycoproteins, with which it shares extensive sequence homology and a similar organization in structural domains, this protein is internally duplicated. Seven of the nine introns in the atpgp1 gene match introns in the mammalian mdr genes to within a few nucleotides, and the positions of these suggest that P-glycoprotein genes evolved by duplication and subsequent fusion of an intron-containing primordial gene prior to the evolutionary separation of plants and mammals. The atpgp1 gene gives rise to transcripts present in all plant parts but particularly abundant in inflorescence axes.
N-cadherin is a transmembrane Ca(2+)-dependent glycoprotein that is part of adherens junctions. I... more N-cadherin is a transmembrane Ca(2+)-dependent glycoprotein that is part of adherens junctions. It functions with the cell adhesion N-terminal extracellular domain as a site of homophilic cell-cell contacts. The intracellular C-terminal domain provides via a catenin complex the interaction with the cytoskeleton. Ectopic expression of chicken N-cadherin in adult rat cardiomyocytes (ARC) in culture was obtained after microinjection into non-dividing cardiomyocytes; it was demonstrated that the exogenous protein colocalized with the endogenous N-cadherin at the plasma membrane of the cell and formed contact sites. A dominant negative chicken N-cadherin mutant was constructed by a large deletion of the extracellular domain. This mutant was expressed and inhibited the function of the endogenous rat N-cadherin probably by competing for the catenin complex binding domain, which is essential for the formation of a stable cell-cell contact of ARC. The injected cells lost contact with neighbo...
Current Plant Science and Biotechnology in Agriculture, 1991
Resistance of wheat (Triticum aestivum L.) to Erysiphe graminis f. sp. tritici (powdery mildew) i... more Resistance of wheat (Triticum aestivum L.) to Erysiphe graminis f. sp. tritici (powdery mildew) is increased following exposure to the incompatible E. g. f. sp. hordei. This resistance response correlates with the activation of certain genes. We have obtained genomic clones of some such genes using induced cDNAs as probes. Sequence analysis indicated that one of our clones encodes a glutathione-S-transferase (GST), an enzyme known to be involved in herbicide detoxification, but which so far has not been associated with response to pathogen attack. A second class of genes encodes a small protein of unknown function. Based on its deduced primary sequence and its high glycine and proline content we speculate that it is an integral membrane protein possibly interacting with the cell wall.
Durante el desarrollo de la hipertensión arterial, las interacciones entre las sobrecargas de pre... more Durante el desarrollo de la hipertensión arterial, las interacciones entre las sobrecargas de presión y de volumen conducen a diferentes patrones de hipertrofia cardíaca y a un aumento de los péptidos natriuréticos (PN). Los perfiles de síntesis y secreción de ANP y BNP se han investigado en modelos de hipertensión arterial; sin embargo, aún no se ha estudiado la evolución diferencial de estos perfiles durante períodos agudos y crónicos de la hipertrofia cardíaca producida por sobrecarga de volumen. Por este motivo estudiamos ratas Sprague- Dawley con el modelo DOCA-sal a las 2, 4, 6 y 12 semanas, correlacionando la evolución de dichos perfiles con la hipertrofia cardíaca y la hipertensión arterial. El grado de hipertrofia cardíaca se correlacionó positivamente con la expresión del ANP en el ventrículo izquierdo y con los niveles de ANP en plasma. La expresión del ANP aumentó a las 4 semanas de tratamiento, mientras que la de BNP se incrementó recién a las 6 semanas. Asimismo, el BN...
RESUMENDurante la hipertensión arterial, las interacciones entre las sobrecargas de presión y vol... more RESUMENDurante la hipertensión arterial, las interacciones entre las sobrecargas de presión y volumenconducen a diferentes patrones de hipertrofia cardíaca y a un aumento de los péptidosnatriuréticos (PN). Los perfiles de síntesis y secreción de ANP y BNP se han investigado enmodelos de hipertensión arterial. Sin embargo, aún no se ha estudiado su evolución diferencialdurante períodos agudos y crónicos de la hipertrofia cardíaca producida por sobrecargade presión. Por este motivo estudiamos ratas Sprague-Dawley con el modelo 1 riñón-1 clip alas 2, 4, 6 y 12 semanas, correlacionando la evolución de dichos perfiles con la hipertrofiacardíaca y la hipertensión arterial.Observamos una correlación positiva entre la elevación de la presión arterial y el grado dehipertrofia cardíaca, presentando ambos parámetros un incremento dependiente del tiempoa partir de las 2 semanas. La expresión del BNP mostró un aumento precoz a las 2semanas de tratamiento, mientras que el ANP se incrementó signif...
The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult ... more The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult heart, and, moreover, indicates that an impaired neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity. Despite this strong data, the specific cardiomyocyte targets of the active erbB2/erbB4 heterodimer remain unknown. In this paper, we examined pathways involved in cardiomyocyte damage as a result of the cardiac sensitization to anthracycline toxicity in the ventricular muscle-specific erbB4 knockout mouse. We performed morphological analyses to evaluate the ventricular remodeling and employed a cDNA microarray to assess the characteristic gene expression profile, verified data by real-time RT-PCR, and then grouped into functional categories and pathways. We confirm the upregulation of genes related to the classical signature of a hypertrophic response, implicating an erbB2-dependent mechanism in doxorubicin-treated erbB4-KO hearts. Our results indicate the remarkab...
Neuregulin-1 (NRG1) signaling through the tyrosine kinase receptors erbB2 and erbB4 is required f... more Neuregulin-1 (NRG1) signaling through the tyrosine kinase receptors erbB2 and erbB4 is required for cardiac morphogenesis, and it plays an essential role in maintaining the myocardial architecture during adulthood. The tyrosine kinase receptor erbB2 was first linked to the amplification and overexpression of erbb2 gene in a subtype of breast tumor cells, which is indicative of highly proliferative cells and likely a poor prognosis following conventional chemotherapy. The development of targeted therapies to block the survival of erbB2positive cancer cells revealed that impaired NRG1 signaling through erbB2/erbB4 heterodimers combined with anthracycline chemotherapy may lead to dilated cardiomyopathy in a subpopulation of treated patients. The ventricular-specific deletion of either erbb2 or erbb4 manifested dilated cardiomyopathy, which is aggravated by the administration of doxorubicin. Based on the exacerbated toxicity displayed by the combined treatment, it is expected that the relevant pathways would be affected in a synergistic manner. This review examines the NRG1 activities that were monitored in different model systems, focusing on the emerging pathways and molecular targets, which may aid in understanding the acquired dilated cardiomyopathy that occurs under the conditions of NRG1-deficient signaling.
Adult rat cardiomyocytes (ARCs) in long-term culture, which show a distinct adaptive flexibility,... more Adult rat cardiomyocytes (ARCs) in long-term culture, which show a distinct adaptive flexibility, are presented as a system to study cardiac cell hypertrophy in vitro. In the first 1-2 weeks after isolation, ARCs undergo a process of de- and redifferentiation during which the cell morphology is remodeled and the myofibrillar apparatus is restructured, accompanied by a cell enlargement. The growing cells spread and eventually establish new cell-cell contacts, which display newly formed intercalated discs; synchronous cell beating is resumed in the resulting tissuelike sheet. During myofibrillogenesis, the early fetal program of gene expression is reactivated for several genes, as is observed during hemodynamic overload hypertrophy. The cells resume hormonal activity and express atrial natriuretic factor (ANF); the expression pattern of ANF is also reminiscent of that seen in hypertrophy. In cells grown in a medium conditioned by 12-day ARCs, though, myofibrillogenesis is accelerated and accompanied by a downregulation of ANF. In a creatine-deficient medium, on the other hand, the ARCs display giant mitochondria with paracrystalline inclusions imitating a situation found, for example, in mitochondrial myopathies.
Winter wheat (Triticum aestivum) shows local, induced resistance against the plant-pathogenic fun... more Winter wheat (Triticum aestivum) shows local, induced resistance against the plant-pathogenic fungus Erysiphe graminis f. sp. tritici following exposure to the nonpathogen E. g. f. sp. hordei. The onset of this resistance has been shown to be correlated with the activation of putative defense genes, and cDNA clones representing transcripts of induced genes have been obtained (P. Schweizer, W. Hunziker, and E. Mösinger, Plant Molecular Biology 12:643-654, 1989). We have cloned and sequenced a gene corresponding to one of these cDNAs, WIR5. Sequence analysis indicated that this gene contains three exons and encodes a protein of 229 amino acids. S1 mapping showed that transcripts homologous to this gene are at least 20 times more abundant in leaves infected 14 hr earlier with E. g. f. sp. hordei than in control leaves. Sequence comparison showed that the WIR5 gene product is highly homologous to glutathione-S-transferases (GSTs; EC 25.1.18) of maize. This, together with the fact that the intron positions of both the wheat gene and the maize GSTI gene are conserved, suggests that the cloned pathogen-induced gene, named GstA1, encodes a wheat glutathione-S-transferase.
Wheat (Triticum aestivum) exhibits local acquired resistance to the powdery mildew pathogen Erysi... more Wheat (Triticum aestivum) exhibits local acquired resistance to the powdery mildew pathogen Erysiphe graminis f. sp. tritici. The resistant state can be induced by a preinoculation with the nonhost pathogen E. g.f. sp. hordei, the barley powdery mildew, and is accompanied by the activation of putative defense genes. Here, we report the sequence of a pathogen-induced gene, WIR1a, and a corresponding cDNA, WIR1, that encode novel defense-related proteins of 88 and 85 amino acids, respectively. Analysis of the primary structure of these proteins predicts them to be integral membrane proteins with extracytoplasmic C-terminal domains rich in proline and glycine, through which the proteins possibly interact with the cell wall.
After its identification by Evans and Nason (1953), nitrate reductase (NR) was shown to be a subs... more After its identification by Evans and Nason (1953), nitrate reductase (NR) was shown to be a substrate inducible enzyme by Tang and Wu (1957). In 1960 Hageman and Flesher demonstrated further that both light and N03-were required for the appearance of nitrate reductase activity (Hageman and Flesher 1960). Since that time there have been many reports confirming the initial observations with light and N03-and conflicting reports concerning the repression of the induction of NR by Nl4+ (Beevers and Hageman 1972; Ullrich 1987). Two factors could be important in the appearance of NR activity. The activation of NR, for example, has been elegantly demonstrated in the green alga Chiorelia by Losada et al. (1970) and by Pistorious et al. (1976). A de novo synthesis of the NR protein in response to N03-has been demonstrated by Amy and Garrett (1979) in Neurospora crassa and this phenomenon may also be important in algae and higher plants. Research in higher plants has emphasized de novo synthesis (Remmler and Campbell 1986). However, there have also been several preliminary reports of a reversible activation of NR in higher plants (Aryan and Wallace 1983; Palacian et al. 1974; Somers et al. 1983). An activation/inactivation phenomenon may, for example, be of importance in light/dark transitions (Campbell 1987) or in the response of NR to drought (Aryan and Wallace 1983). The ability to purify NR (Solomonson 1985), and to prepare antibodies to that protein allows us to quantitate the protein either by the ELISA method (Campbell and Remmler 1986) or by SDS-PAGE followed by immunoblotting (Oaks et al. 1988). Thus with an improved system we were able to confirm the early results with light and N03-on the appearance ofNR activity. A 116 kD protein which reacts with polyclonal antibody raised against a pure NR from maize leaves is also present in crude extracts prepared from light-grown but not in dark-grown seedling shoots (Oaks et al. 1988). At this stage of the investigation we can conclude either that this polypeptide is not made in the dark or that it is very unstable in dark-grown seedlings. The induction of the NR protein was apparent in the absence of N03-in the light. The explanation for this unexpected observation turned out to be an induction system in maize that is extremely sensitive to low levels of external N03-. Sufficient levels of N03-are present in sand, vermiculite and Kimpack papers (Oaks et al. 1988). In a hydroponic system,
Current Plant Science and Biotechnology in Agriculture, 1987
Until recently the study of nitrogen fixation genes from Rhizobium has focused either on nif gene... more Until recently the study of nitrogen fixation genes from Rhizobium has focused either on nif genes as they have been defined in Klebsiella pneumoniae (Dixon, 1984), or on fix genes closely linked to nif genes (such as fixABC, Puhler et al., 1984; Ausubel et al., 1985). However we may expect some non nif functions to be important for nitrogen fixation in planta: differentiation of bacteria into bacteroids, bacteroid specific metabolic functions, Rhizobium-dependent nodule maturation, plant dependent regulation of bacteroid functions.
When present in Escherichia coli on the multicopy expression vector pUC19, a Rhizobium meliloti r... more When present in Escherichia coli on the multicopy expression vector pUC19, a Rhizobium meliloti regulatory gene, fixJ, belonging to a two-component regulatory system, activated the expression of two R. meliloti symbiotic genes, nifA and fixK. Primer extension by reverse transcription showed that FixJ stimulates nifA expression in E. coli by activating pnifA.
The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition... more The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac...
Las cianobacterias, las algas y las plantas superiores son capaces de captar la energia luminica ... more Las cianobacterias, las algas y las plantas superiores son capaces de captar la energia luminica para la reduccion fotosintetica de C02 a (CH20) utilizando H20 como reductor. Este proceso se lleva a cabo en el caso de las plantas superiores en organelas especializadas, los cloroplastos, los cuales contienen los pigmentos que absorben la luz distribuidos en vesiculas membranosas (tilacoides). Una vez captada, la energia luminica es covertida en energia electroquimica en la cadena fotosintetica de transporte de eletrones. En este proceso se generan ATP y NADPH, los cuales son utilizados por las enzimas del ciclo de Benson-Calvin (ciclo reductivo de las pentosas fosfato), localizadas en la porcion soluble del cloroplasto (estroma), para la fijacion del C02. Estas enzimas, a excepcion de la fosforribuloquinasa y la ribulosa-1,5-bisfosfato carboxilasa (la proteina mas abundante en la naturaleza) estan distribuidas ampliamente entre los organismos vivos y actuan tanto en la sintesis como ...
Multidrug resistance of mammalian tumor cells is caused by the enhanced expression of P-glycoprot... more Multidrug resistance of mammalian tumor cells is caused by the enhanced expression of P-glycoproteins. These proteins are encoded by mdr genes and mediate the energy-dependent efflux of a variety of lipophilic drugs from cells. To test whether in plants mdr-like genes might be involved in certain cases of cross-resistance to different herbicides, we have cloned and characterized a gene from Arabidopsis thaliana, atpgp1, encoding a putative P-glycoprotein homologue. Like the mammalian P-glycoproteins, with which it shares extensive sequence homology and a similar organization in structural domains, this protein is internally duplicated. Seven of the nine introns in the atpgp1 gene match introns in the mammalian mdr genes to within a few nucleotides, and the positions of these suggest that P-glycoprotein genes evolved by duplication and subsequent fusion of an intron-containing primordial gene prior to the evolutionary separation of plants and mammals. The atpgp1 gene gives rise to transcripts present in all plant parts but particularly abundant in inflorescence axes.
N-cadherin is a transmembrane Ca(2+)-dependent glycoprotein that is part of adherens junctions. I... more N-cadherin is a transmembrane Ca(2+)-dependent glycoprotein that is part of adherens junctions. It functions with the cell adhesion N-terminal extracellular domain as a site of homophilic cell-cell contacts. The intracellular C-terminal domain provides via a catenin complex the interaction with the cytoskeleton. Ectopic expression of chicken N-cadherin in adult rat cardiomyocytes (ARC) in culture was obtained after microinjection into non-dividing cardiomyocytes; it was demonstrated that the exogenous protein colocalized with the endogenous N-cadherin at the plasma membrane of the cell and formed contact sites. A dominant negative chicken N-cadherin mutant was constructed by a large deletion of the extracellular domain. This mutant was expressed and inhibited the function of the endogenous rat N-cadherin probably by competing for the catenin complex binding domain, which is essential for the formation of a stable cell-cell contact of ARC. The injected cells lost contact with neighbo...
Current Plant Science and Biotechnology in Agriculture, 1991
Resistance of wheat (Triticum aestivum L.) to Erysiphe graminis f. sp. tritici (powdery mildew) i... more Resistance of wheat (Triticum aestivum L.) to Erysiphe graminis f. sp. tritici (powdery mildew) is increased following exposure to the incompatible E. g. f. sp. hordei. This resistance response correlates with the activation of certain genes. We have obtained genomic clones of some such genes using induced cDNAs as probes. Sequence analysis indicated that one of our clones encodes a glutathione-S-transferase (GST), an enzyme known to be involved in herbicide detoxification, but which so far has not been associated with response to pathogen attack. A second class of genes encodes a small protein of unknown function. Based on its deduced primary sequence and its high glycine and proline content we speculate that it is an integral membrane protein possibly interacting with the cell wall.
Durante el desarrollo de la hipertensión arterial, las interacciones entre las sobrecargas de pre... more Durante el desarrollo de la hipertensión arterial, las interacciones entre las sobrecargas de presión y de volumen conducen a diferentes patrones de hipertrofia cardíaca y a un aumento de los péptidos natriuréticos (PN). Los perfiles de síntesis y secreción de ANP y BNP se han investigado en modelos de hipertensión arterial; sin embargo, aún no se ha estudiado la evolución diferencial de estos perfiles durante períodos agudos y crónicos de la hipertrofia cardíaca producida por sobrecarga de volumen. Por este motivo estudiamos ratas Sprague- Dawley con el modelo DOCA-sal a las 2, 4, 6 y 12 semanas, correlacionando la evolución de dichos perfiles con la hipertrofia cardíaca y la hipertensión arterial. El grado de hipertrofia cardíaca se correlacionó positivamente con la expresión del ANP en el ventrículo izquierdo y con los niveles de ANP en plasma. La expresión del ANP aumentó a las 4 semanas de tratamiento, mientras que la de BNP se incrementó recién a las 6 semanas. Asimismo, el BN...
RESUMENDurante la hipertensión arterial, las interacciones entre las sobrecargas de presión y vol... more RESUMENDurante la hipertensión arterial, las interacciones entre las sobrecargas de presión y volumenconducen a diferentes patrones de hipertrofia cardíaca y a un aumento de los péptidosnatriuréticos (PN). Los perfiles de síntesis y secreción de ANP y BNP se han investigado enmodelos de hipertensión arterial. Sin embargo, aún no se ha estudiado su evolución diferencialdurante períodos agudos y crónicos de la hipertrofia cardíaca producida por sobrecargade presión. Por este motivo estudiamos ratas Sprague-Dawley con el modelo 1 riñón-1 clip alas 2, 4, 6 y 12 semanas, correlacionando la evolución de dichos perfiles con la hipertrofiacardíaca y la hipertensión arterial.Observamos una correlación positiva entre la elevación de la presión arterial y el grado dehipertrofia cardíaca, presentando ambos parámetros un incremento dependiente del tiempoa partir de las 2 semanas. La expresión del BNP mostró un aumento precoz a las 2semanas de tratamiento, mientras que el ANP se incrementó signif...
The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult ... more The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult heart, and, moreover, indicates that an impaired neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity. Despite this strong data, the specific cardiomyocyte targets of the active erbB2/erbB4 heterodimer remain unknown. In this paper, we examined pathways involved in cardiomyocyte damage as a result of the cardiac sensitization to anthracycline toxicity in the ventricular muscle-specific erbB4 knockout mouse. We performed morphological analyses to evaluate the ventricular remodeling and employed a cDNA microarray to assess the characteristic gene expression profile, verified data by real-time RT-PCR, and then grouped into functional categories and pathways. We confirm the upregulation of genes related to the classical signature of a hypertrophic response, implicating an erbB2-dependent mechanism in doxorubicin-treated erbB4-KO hearts. Our results indicate the remarkab...
Neuregulin-1 (NRG1) signaling through the tyrosine kinase receptors erbB2 and erbB4 is required f... more Neuregulin-1 (NRG1) signaling through the tyrosine kinase receptors erbB2 and erbB4 is required for cardiac morphogenesis, and it plays an essential role in maintaining the myocardial architecture during adulthood. The tyrosine kinase receptor erbB2 was first linked to the amplification and overexpression of erbb2 gene in a subtype of breast tumor cells, which is indicative of highly proliferative cells and likely a poor prognosis following conventional chemotherapy. The development of targeted therapies to block the survival of erbB2positive cancer cells revealed that impaired NRG1 signaling through erbB2/erbB4 heterodimers combined with anthracycline chemotherapy may lead to dilated cardiomyopathy in a subpopulation of treated patients. The ventricular-specific deletion of either erbb2 or erbb4 manifested dilated cardiomyopathy, which is aggravated by the administration of doxorubicin. Based on the exacerbated toxicity displayed by the combined treatment, it is expected that the relevant pathways would be affected in a synergistic manner. This review examines the NRG1 activities that were monitored in different model systems, focusing on the emerging pathways and molecular targets, which may aid in understanding the acquired dilated cardiomyopathy that occurs under the conditions of NRG1-deficient signaling.
Adult rat cardiomyocytes (ARCs) in long-term culture, which show a distinct adaptive flexibility,... more Adult rat cardiomyocytes (ARCs) in long-term culture, which show a distinct adaptive flexibility, are presented as a system to study cardiac cell hypertrophy in vitro. In the first 1-2 weeks after isolation, ARCs undergo a process of de- and redifferentiation during which the cell morphology is remodeled and the myofibrillar apparatus is restructured, accompanied by a cell enlargement. The growing cells spread and eventually establish new cell-cell contacts, which display newly formed intercalated discs; synchronous cell beating is resumed in the resulting tissuelike sheet. During myofibrillogenesis, the early fetal program of gene expression is reactivated for several genes, as is observed during hemodynamic overload hypertrophy. The cells resume hormonal activity and express atrial natriuretic factor (ANF); the expression pattern of ANF is also reminiscent of that seen in hypertrophy. In cells grown in a medium conditioned by 12-day ARCs, though, myofibrillogenesis is accelerated and accompanied by a downregulation of ANF. In a creatine-deficient medium, on the other hand, the ARCs display giant mitochondria with paracrystalline inclusions imitating a situation found, for example, in mitochondrial myopathies.
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Papers by Cecilia Hertig