PubMed Health⌕ Search

Biomedical subjects

P Reisdorf

Publications and source records attributed to P Reisdorf.

10 recordsLinked to original sources
PubMed2001

Alteration of transforming growth factor-beta1 response involves down-regulation of Smad3 signaling in myofibroblasts from skin fibrosis.

Fibrosis is an unregulated tissue repair process whose predominant characteristics are the proliferation of myofibroblasts and an excessive deposition of extracellular matrix. Transforming growth factor (TGF)-beta1 is considered as one of the most fibrogenic cytokines. However, the molecular mechanisms involved in its profibrotic role are not fully understood. Here, we addressed the role of TGF-beta1 on cell proliferation and intracellular signal transduction in a pig model of skin fibrosis induced by gamma-irradiation. Primary myofibroblasts were isolated from the fibrotic tissue and their response to TGF-beta1 was compared to that of normal skin fibroblasts. The present results show that the differentiation of myofibroblasts involves a lack of TGF-beta1 growth inhibition and an impaired TGF-beta1 signaling. Receptor activity and Smad2/4 or Smad3/4 complex formation were similar in both cell types after TGF-beta1 treatment. However, the translocation of Smad3 protein into the nucleus was reduced in myofibroblasts as compared to that in fibroblasts, as well as its binding to target DNA sequences and the activation of the Smad binding elements found in the PAI-1. Interestingly, Smad2 was translocated similarly to the nucleus in both cell types suggesting that this protein may function normally in myofibroblasts. We propose that uncoupling of antiproliferative and profibrotic actions of TGF-beta1 in fibrosis may occur through differential regulation of the activities of Smad2 and Smad3 transcription factors.

Animals↗
PubMed2000

Human and mouse Fas (APO-1/CD95) death receptor genes each contain a p53-responsive element that is activated by p53 mutants unable to induce apoptosis.

p53 is a tumor suppressor protein that induces apoptosis at least in part through its ability to act as a sequence-specific transactivator. This work reports that intron 1 of the mouse Fas death receptor gene contains a p53-responsive element (p53RE) that matches the p53 consensus sequence and that is located between nucleotides +1704 and +1723 from the transcription initiation site. This element is specifically bound by p53 and functions as a p53-dependent enhancer in mammalian or in yeast reporter gene assays. Contrary to bax, another known pro-apoptotic p53-target gene, both mouse and human FAS p53REs are still activated by the discriminatory p53 mutants Pro-175 and Ala-143, a class of mutants unable to induce apoptosis. We propose that p53-dependent up-regulation of Fas does not induce apoptosis per se but sensitizes the cell to other pro-apoptotic signal(s). The functional conservation of p53-dependent Fas up-regulation argues strongly in favor of its biological importance and suggests that murine models may be used to study further the in vivo role of Fas in the p53 response.

Animals↗
PubMed1998

Mechanisms of p53-induced apoptosis: in search of genes which are regulated during p53-mediated cell death.

The tumor suppressor gene p53 is a major player in the protection of cells from DNA damage. In the majority of human cancers, p53 is functionally inactivated--mostly by mutations but also by interaction with viral or cellular proteins. Wild-type p53 is involved in essential functions such as DNA repair, transcription, genomic stability, senescence, cell cycle control and apoptosis. It was shown to be a sequence-specific transcriptional activator, and this activity appears to be necessary to impose growth arrest. A major target gene which participates in p53-mediated growth arrest is p21/Waf1, an inhibitor of cyclin-dependent kinases. Whether or not transcriptional activation of target genes is required for p53-mediated apoptosis may depend on the cell type and external factors, and the mechanism of cell death induction is not clear yet. We have employed clones of the M1 myeloid leukemic cell line expressing a temperature-sensitive p53 mutant to study genes which are regulated during p53-induced apoptosis.

Animals↗
PubMed1997

The MBR1 gene from Saccharomyces cerevisiae is activated by and required for growth under sub-optimal conditions.

The MBR1 gene was isolated as a multicopy suppressor of the phenotype on glycerol medium of a Saccharomyces cerevisiae strain mutant for the Hap2/3/4/5 transactivator complex. In this paper, we show that Mbr1p is a limiting factor for growth on glycerol medium under the following sub-optimal culture conditions: in late growth phase, at low temperature, at high external pH or in the presence of 1,10-phenanthroline. Moreover, deletion of MBR1 protects cells against stress, whilst overexpression of this gene has the opposite effect. MBR1 expression is induced in the late growth phase and is negatively controlled by the cAMP-dependent protein kinase A (PKA). Both activation of PKA or overexpression of SOK1 or SCH9-two genes isolated as multicopy suppressors of a PKA null mutant-suppress the mbr1 growth defect. Our results indicate that Mbr1p is not an essential element of any one of these pathways. Deletion of SAC1, a gene implicated in vesicular transport, in association with MBR1 deletion, causes synthetic lethality. A possible role of Mbr1p in intracellular trafficking is discussed.

Bacterial Proteins↗
PubMed1994

MBR1 and MBR3, two related yeast genes that can suppress the growth defect of hap2, hap3 and hap4 mutants.

Two new yeast genes, named MBR1 and MBR3, were isolated as multicopy suppressors of the growth defect of a strain lacking the HAP2 transcriptional activator. Both genes when overexpressed can also suppress the growth defect of hap3 and hap4 null mutants. However, overexpression of MBR1 cannot substitute for the HAP2/3/4 complex in activation of the CYC1 gene. Nucleotide sequencing of MBR1 and MBR3 revealed that these two genes encode serine-rich, hydrophilic proteins with regions of significant homology. The functional importance of one of these conserved regions was shown by mutagenesis. Disruption of MBR1 leads to a partial growth defect on glycerol medium. Disruption of MBR3 has no major effect but the double disruptant shows a synthetic phenotype suggesting that the MBR1 and MBR3 gene products participate in common function.

Amino Acid Sequence↗
PubMed1993

Enhanced in vivo monooxygenase activities of mammalian P450s in engineered yeast cells producing high levels of NADPH-P450 reductase and human cytochrome b5.

We have engineered yeast genomic DNA to construct a set of strains producing various relative amounts of yeast NADPH-P450 reductase (Yred) and human cytochrome b5 (Hb5). Expression of cDNAs encoding human P450 1A1, 1A2, 3A4, 19A and mouse P450 1A1 in the different oxido-reduction backgrounds thus constituted were achieved after strain transformation by plasmid-based P450-encoding expression cassettes. The results indicate that the level of Yred strongly affects all activities tested. In contrast, the amount of Hb5 affects activities in a manner that is dependent both on the P450 isoform considered and the Yred level. In a strain containing optimized amounts of Hb5 and Yred, human P450 3A4-specific testosterone-6 beta-hydroxylase activity can be enhanced as much as 73-fold in comparison with the activity observed in a wild-type strain. Bioconversion of sterols or xenobiotics was easily achieved in vivo using this new co-expression system.

Animals↗
PubMed1993

Epitope-tagging vectors designed for yeast.

In order to facilitate the process of epitope-tagging of yeast proteins, we have constructed two Saccharomyces cerevisiae-Escherichia coli shuttle vectors that allow fusion of a sequence encoding an epitope of the human c-myc protein at the 3' end of any gene. An example of the use of this technique is presented.

Amino Acid Sequence↗
PubMed1992

Individual differences in bridging inference processes.

The role of individual differences in bridging-inference processing was studied. Students (n = 135) read passages of short to moderate length. After each one, they answered corresponding questions about inferences that bridged causally related ideas that were either near or far apart in the text. The main hypothesis was that local bridging-inference processing is facilitated by the reader's predisposition to access pertinent knowledge during comprehension. Regression analyses provided support for this proposal and indicated that greater working-memory capacity and vocabulary knowledge promote inference processing. The following relationships between the predictors and inference processing were proposed: Knowledge access promotes the co-occurrence in working memory of the text ideas and knowledge needed to compute the bridge. Working-memory capacity enhances the likelihood that needed antecedent ideas will be available to the bridging processes. Vocabulary knowledge may promote inference processing because unfamiliar word meanings place more demands on working-memory resources than do familiar meanings.

Adult↗
PubMedDate not supplied

[Radiation-induced superficial fibrosis and TGF-alpha 1].

Radiation-induced fibrosis is a late sequela of both therapeutic and accidental irradiations, which has been described in various tissues, including the lung, liver, kidney and skin. This review presents different aspects of superficial radiation-induced fibrosis, such as clinical observations, histological changes, cellular and molecular regulations, and medical management. Recent evidence on the critical role played by TGF-beta 1 in the initiation, development and persistence of fibrosis are discussed, as well as the possibility that this cytokine may constitute a specific target for antifibrotic agents.

Animals↗