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Sanaa Choufani

Publications and source records attributed to Sanaa Choufani.

8 recordsLinked to original sources
PubMed2006

Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome.

We recently reported the disruption of the inner mitochondrial membrane peptidase 2-like (IMMP2L) gene by a chromosomal breakpoint in a patient with Gilles de la Tourette syndrome (GTS). In the present study we sought to identify genetic variation in IMMP2L, which, through alteration of protein function or level of expression might contribute to the manifestation of GTS. We screened 39 GTS patients, and, due to the localization of IMMP2L in the critical region for the autistic disorder (AD) locus on chromosome 7q (AUTS1), 95 multiplex AD families; however, no coding mutations were found in either GTS or AD patients. In addition, no parental-specific expression of IMMP2L was detected in somatic cell hybrids containing human chromosome 7 and human cell lines carrying a maternal uniparental disomy for chromosome 7 (mUPD7). Despite the fact that no deleterious mutations in IMMPL2 (other than the inverted duplication identified previously) were identified in either GTS or AD, this gene cannot be excluded as a possible rare cause of either disorder.

Autistic Disorder↗
PubMed2003

Human chromosome 7: DNA sequence and biology.

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.

Animals↗
PubMed2003

Activation of sarcolemma and nuclear membranes ET-1 receptors regulates transcellular calcium levels in heart and vascular smooth muscle cells.

The use of an ET-1 fluorescent probe in human heart and vascular smooth muscle cells showed that ET-1 receptors are present at both the sarcolemma and nuclear envelope membranes. The use of immunofluorescence studies showed that the ETA receptor was mainly present at the sarcolemma and cytosolic levels. However, the ETB receptor was present at the sarcolemma and the cytosol, as well as the nuclear envelope membranes and the nucleoplasm. In addition, ET-1 immunoreactivity was seen in the cytosol and the nucleus. Using Ca2+ fluorescent probes such as Fluo-3, Indo 1, and yellow cameleon, as well as confocal microscopy three-dimensional image measurement technique, stimulation of ET-1 receptors at the sarcolemma membranes induced an increase of cytosolic and nuclear free Ca2+ levels. This effect of extracellular ET-1 was blocked by removal of extracellular calcium. Direct stimulation of ET-1 receptors at the nuclear envelope membranes also induced an increase of intranuclear free Ca2+ level. Our results suggest that the stimulation of sarcolemmal Ca2+ influx by ET-1 seems to be due to the activation of ETA and ETB receptors. However, the increase of nucleoplasmic Ca2+ levels by cytosolic ET-1 seems to be mediated via the activation of ETB receptors. Activation of nuclear membranes ETB receptors seems to prevent nuclear Ca2+ overload and may protect the cell from apoptosis.

Calcium↗
PubMed2002

Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor.

It has been postulated that intracellular binding sites for platelet-activating factor (PAF) contribute to proinflammatory responses to PAF. Isolated nuclei from porcine cerebral microvascular endothelial cells (PCECs) produced PAF-molecular species in response to H(2)O(2). Using FACS analysis, we demonstrated the expression of PAF receptors on cell and nuclear surfaces of PCECs. Confocal microscopy studies performed on PCECs, Chinese hamster ovary cells stably overexpressing PAF receptors, and isolated nuclei from PCECs also showed a robust nuclear distribution of PAF receptors. Presence of PAF receptors at the cell nucleus was further revealed in brain endothelial cells by radioligand binding experiments, immunoblotting, and in situ in brain by immunoelectron microscopy. Stimulation of nuclei with methylcarbamate-PAF evoked a decrease in cAMP production and a pertussis toxin-sensitive rise in nuclear calcium, unlike observations in plasma membrane, which exhibited a pertussis toxin-insensitive elevation in inositol phosphates. Moreover, on isolated nuclei methylcarbamate-PAF evoked the expression of proinflammatory genes inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) and was associated with augmented extracellular signal-regulated kinase 1/2 phosphorylation and NF-kappaB binding to the DNA consensus sequence. COX-2 expression was prevented by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 and NF-kappaB inhibitors. This study describes for the first time the nucleus as a putative organelle capable of generating PAF and expresses its receptor, which upon stimulation induces the expression of the proinflammatory gene COX-2.

Animals↗
PubMed2002

Regulation of eNOS expression in brain endothelial cells by perinuclear EP(3) receptors.

We reported upregulation of endothelial nitric oxide synthase (eNOS) by PGE(2) in tissues and presence of perinuclear PGE(2) receptors (EP). We presently studied mechanisms by which PGE(2) induces eNOS expression in cerebral microvessel endothelial cells (ECs). 16,16-Dimethyl PGE(2) and selective EP(3) receptor agonist M&B28767 increased eNOS expression in ECs and the NO-dependent vasorelaxant responses induced by substance P on cerebral microvessels. These effects could be prevented by prostaglandin transporter blocker bromcresol green and actinomycin D. EP(3) immunoreactivity was confirmed on plasma and perinuclear membrane of ECs. M&B28767 increased eNOS RNA expression in EC nuclei, and this effect was augmented by overexpression of EP(3) receptors. M&B28767 also induced increased phosphorylation of Erk-1/2 and Akt, as well as changes in membrane potential revealed by the potentiometric fluorescent dye RH421, which were prevented by iberiotoxin; perinuclear K(Ca) channels were detected, and their functionality corroborated by NS1619-induced Ca(2+) signals and nuclear membrane potential changes. Moreover, pertussis toxin, Ca(2+) chelator, and channel blockers EGTA, BAPTA, and SK&F96365, as well as K(Ca) channel blocker iberiotoxin, protein-kinase inhibitors wortmannin and PD 98059, and NF-kappaB inhibitor pyrrolidine dithiocarbamate prevented M&B28767-induced increase in Ca(2+) transients and/or eNOS expression in EC nuclei. We describe for the first time that PGE(2) through its access into cell by prostaglandin transporters induces eNOS expression by activating perinuclear EP(3) receptors coupled to pertussis toxin-sensitive G proteins, a process that depends on nuclear envelope K(Ca) channels, protein kinases, and NF-kappaB; the roles for nuclear EP(3) receptors seem different from those on plasma membrane.

Animals↗
PubMed2002

Delta ribozyme benefits from a good stability in vitro that becomes outstanding in vivo.

The stability of a trans-acting delta ribozyme was studied under various conditions. Although in vitro (i.e., in the presence of protein extracts) this delta ribozyme appears to be only slightly more stable than a hammerhead ribozyme, in vivo (i.e., after cell transfection) it exhibits an outstanding stability that manifests itself in the calculated half-life of over 100 h regardless of the means of transfection. The P2 stem, which includes both the 5' and 3' ends, is shown to play a critical role in this stability. Direct mutagenesis of the most nuclease susceptible nucleotides failed to generate a more stable ribozyme that retained the same catalytic potential. Clearly, delta ribozyme appears to be well adapted to the human cell environment, and is therefore ideal for the development of a gene-inactivation system.

Base Sequence↗
PubMed2002

Role of endothelin-1 receptors in the sarcolemma membrane and the nuclear membrane in the modulation of basal cytosolic and nuclear calcium levels in heart cells.

Our previous work in heart cells showed that the nuclear envelope membranes possess receptors, such as those for angiotensin II. Using non-working single cells from the hearts of 10-day chick embryos and the confocal microscopy technique, our present results show that stimulation of endothelin-1 (ET-1) receptors at the sarcolemma membrane induced a dose-dependent sustained increase in basal cytosolic and nuclear calcium levels that was insensitive to the ET(A) and ET(B) receptor antagonists BQ123 and BQ788. The cytosolic application of ET-1 induced a dose-dependent increase in the sustained basal nuclear Ca(2+) concentration that was insensitive to BQ123 and BQ788. The ET-1 receptors at the nuclear envelope membrane were more sensitive to ET-1 than those located at the sarcolemma membrane of heart cells. Cytosolic application of ET-1 prevented sustained basal cytosolic Ca(2+) uptake by the nuclei. The use of an ET-1 fluorescent probe demonstrated the presence of ET-1 receptors at both the sarcolemma membrane and the nuclear envelope membrane. Thus our results suggest that ET-1 receptors that are insensitive to BQ123 and BQ788 are present at both the sarcolemma and nuclear envelope membranes. Extracellular and cytosolic ET-1 may play a role in regulating basal cytosolic and nuclear Ca(2+) levels in heart cells.

Animals↗