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N Lomri

Publications and source records attributed to N Lomri.

26 records · Page 2Linked to original sources
PubMed1989

Effects of altered thyroid states and undernutrition on the calbindin-D28K (calcium-binding protein) content of the hippocampal formation in the developing rat.

A quantitative study of calbindin-D28K (calcium-binding protein) was carried out on the developing hippocampal formation in normal, hypothyroid, hyperthyroid, and underfed rats. In normal animals, the calbindin-D28K content increased after birth in agreement with the distribution of the protein previously reported by immunocytochemistry. Calbindin-D28K was strikingly spared, compared to the other proteins, from the effects of hypothyroidism. On the contrary, the calbindin-D28K:protein ratio was transiently reduced by hyperthyroidism. Corrective doses of thyroxine to hypothyroid rats increased the calbindin-D28K content whatever the period of the hormonal treatment, but they also had a marked effect on the hippocampal weight and the protein content, especially when the hormone was given on days 2-3. With this latter replacement therapy schedule, the calbindin-D28K:protein ratio dropped from the high value of the hypothyroid animal to normal. Taken together, the results obtained in hypothyroidism, hyperthyroidism and replacement therapy are consistent with a pronounced action of thyroid hormone on hippocampal structures other than those containing calbindin-D28K. Undernutrition, which, like hypo- or hyperthyroidism, also markedly impairs hippocampal growth, affected the calbindin-D28K content per hippocampus but not the calbindin-D28K:protein ratio. This emphasizes the unique influence of thyroid hormone on brain development. The relative preservation of calbindin-D28K in the hippocampal formation of animals lacking thyroid hormone suggests that calbindin-D28K function may be crucial in this brain region.

Animals↗
PubMed1988

The rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene. Complete nucleotide sequence and structural organization.

The structural organization of the entire rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene was determined by analysis of overlapping genomic clones isolated from a rat genomic library using the rat 9-kDa CaBP cDNA [Desplan C., Heidmann O., Lillie J., Auffray C. and Thomasset M. (1983) J. Biol. Chem. 258, 13502-13505]. These clones together span 30 kbp of rat genomic DNA, with the rat 9-kDa CaBP gene lying in the middle. The 9-kDa CaBP gene is 2.5 kbp long and contains three exons interrupted by two introns. The first exon contains almost the entire 5' untranslated region. The second exon codes for the calcium-binding site I, the third exon codes for site II and the 3' untranslated region. Therefore each of the calcium-binding domains is encoded by single, separate exons. The transcription initiation site was identified by S1 nuclease mapping and primer extension. A consensus sequence TATAAA is localized 31 bp upstream from the cap site and the 'CCAAT-box' lies upstream from the transcription start. Single (AC)25 and (AG)23 repeats are present in the second intron together with an Alu-like sequence. Repetitive elements are present 5 kbp upstream from the cap site and in the 3' flanking region. Comparison of the known rat CaBP sequences (9-kDa CaBP, 28-kDa CaBP, S100 protein) shows that the 9-kDa CaBP is more closely related to the S100 protein than to the 28-kDa CaBP. There is no evidence to indicate that 9-kDa CaBP has arisen from the 28-kDa CaBP.

Amino Acid Sequence↗
PubMed1988

Evolution of the EF-hand calcium-binding protein family: evidence for exon shuffling and intron insertion.

The evolutionary history of the intracellular calcium-binding protein superfamily is well documented. The members of this gene family are all believed to be derived from a common ancestor, which, itself, was the product of two successive gene duplications. In this study, we have compared and analyzed the structures of the recently described genes coding for these proteins. We propose a series of evolutionary events, which include exon shuffling and intron insertion, that could account for the evolutionary origin of all the members of this superfamily. According to this hypothesis, the ancestral gene, a product of two successive duplications, consisted of at least four exons. Each exon coding for a peptide (a calcium-binding domain) was separated by an intron that had mediated the duplication. Each distinct lineage evolved from this ancestor by genomic rearrangement, with insertion of introns being a prominent feature.

Amino Acid Sequence↗
PubMed1987

Transcriptional and post-transcriptional regulation of vitamin D-dependent calcium-binding protein gene expression in the rat duodenum by 1,25-dihydroxycholecalciferol.

Regulation of the expression of vitamin D-dependent calcium-binding protein (Mr 9000 CaBP) gene by 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in the rat duodenum. In vivo stimulation of Mr 9000 CaBP synthesis was analyzed using a complementary DNA probe and by measuring the rate of Mr 9000 CaBP gene transcription in isolated nuclei (run-on assay). A single 1,25-(OH)2D3 injection (650 pmol/100 g of body weight) induced a 2-fold increase in Mr 9000 CaBP gene transcription within 15 min in the duodenum of vitamin D-deficient rats. RNA synthesis was maximal at 1 h, then decreased until 16 h of postinjection. There was an initial transient accumulation of Mr 9000 CaBP mRNA (from 7 to 15 min), which was followed by a second, significant increase, by 3 h which remained elevated until 16 h. The magnitude and time course of the Mr 9000 CaBP increase was similar to that of its mRNA as early as 1 h after 1,25-(OH)2D3 administration. Mr 9000 CaBP gene transcription was not significantly induced by 1,25-(OH)2D3 in vitamin D-replete rats and no transient accumulation of Mr 9000 CaBP mRNA was observed. Thus, 1,25-(OH)2D3 modulates Mr 9000 CaBP gene expression in at least two ways, a rapid transcriptional stimulation and a post-transcriptional effect preventing degradation of Mr 9000 CaBP transcripts and accounting for their accumulation several hours after the hormone treatment.

Animals↗
PubMed1986

1 alpha, 25-dihydroxyvitamin D3 modulates the growth of 3T3 cells and human skin fibroblasts stimulated by platelet-derived growth factor.

We investigated the effect of 1 alpha,25-dihydroxyvitamin D3 (1,25 (OH)2 vit D3) on the 3H-thymidine uptake by Balb/c 3T3 cells and by human skin fibroblasts stimulated by normal human serum or by purified PDGF. We found an inhibitory effect of 1,25 (OH)2 vit D3 on the DNA synthesis of Balb/c 3T3 cells grown in the presence of human serum as well as in the presence of PDGF. At 5% human serum this effect is minimal at 10(-12) M 1,25 (OH)2 vit D3 and is maximal at 10(-9) M. On the DNA synthesis of human fibroblasts stimulated by human serum or by PDGF a modulatory effect of 1,25 (OH)2 vit D3 was shown. On these cells the vitamin had a stimulatory effect between 10(-11) and 10(-9) M and an inhibitory effect at very high concentrations (10(-7) M). Our results suggested that the effect of 1,25 (OH)2 vit D3 on fibroblast DNA synthesis could be mediated by interactions with its specific intracellular receptor. 1,25 (OH)2 vit D3 had no any action on the growth of human fibroblasts stimulated by fibroblast growth factor.

Animals↗
PubMedDate not supplied

Expression in Escherichia coli of the flavin-containing monooxygenase D (form II) from adult human liver: determination of a distinct tertiary amine substrate specificity.

The cDNA for a major component of the family of flavin-containing monooxygenases (FMOs) present in adult human liver (i.e., HLFMO-D) has been cloned and expressed in a prokaryotic system. Escherichia coli strain NM522 was transformed with pTrcHLFMO-D, and the HLFMO-D cDNA was expressed under the control of the Trc promoter. A variety of tertiary amine substrates [i.e., chlorpromazine and 10-[(N,N-dimethylamino)alkyl]- 2-(trifluoromethyl)phenothiazines] were efficiently oxygenated by HLFMO-D cDNA expressed in E. coli or by adult human liver microsomes. Approximate dimensions of the substrate binding channel for both adult human liver microsomal FMO and cDNA-expressed HLFMO-D were apparent from an examination of the N-oxygenation of a series of 10-[(N,N-dimethylamino)alkyl]-2-(trifluoromethyl)phenothiazines. The substrate regioselectivity studies suggest that adult human liver FMO form D possesses a distinct substrate specificity compared with form A FMO from animal hepatic sources. It is likely that the substrate specificity observed for cDNA-expressed adult human liver FMO-D may have consequences for the metabolism and distribution of tertiary amines and phosphorus- and sulfur-containing drugs in humans and may provide insight into the physiologic substrate(s) for adult human liver FMO.

Animals↗
PubMedDate not supplied

Regio- and stereoselective oxygenations by adult human liver flavin-containing monooxygenase 3. Comparison with forms 1 and 2.

The cDNA for the adult human liver flavin-containing monooxygenase (form 3) (FMO3) was cloned, sequenced, and expressed in Escherichia coli. The cDNA-expressed FMO3 was used to investigate the regio- and stereoselective N- and S-oxygenation of a number of tertiary amines and sulfides, respectively. For comparison, the N- and S-oxygenation of the same chemicals and drugs were examined with adult human liver microsomes from a normal healthy female donor and FMO1 from pig liver and FMO2 from rabbit lung. Both cDNA-expressed FMO3 and adult human liver microsomes N-oxygenated trifluoperazine or 10-(N,N-dimethylaminoalkyl)-phenothiazines with similar substrate specificities. The substrate specificity for FMO3 differed, however, from that of pig liver FMO1. Nucleophilic sulfur-containing compounds [i.e., thiobenzamide, (4-bromophenyl)-1,3-oxathiolane, and 2-methyl-1,3-benzodithiole] were efficiently S-oxygenated by cDNA-expressed FMO3 and adult human liver microsomes. Stereoselective S-oxygenation of (+)- and (-)-(4-bromophenyl)-1,3-oxathiolane and 2-methyl-1,3-benzodithiole was therefore investigated. In general, the stereoselectivity observed for S-oxygenation in the presence of FMO3 was similar to that observed in the presence of adult human liver microsomes. In most cases examined, however, the stereoselectivity for S-oxygenation was quite distinct from that observed for pig liver FMO1. We conclude that FMO3 is the major form of FMO active in adult human liver. Because the stereoselectivity for X-oxygenation and the substrate specificity for tertiary amine N-oxygenation by cDNA-expressed FMO3 are distinct from those of pig liver FMO1, we conclude that the binding channel for each isoform is quite different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗