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Biomedical subjects

M D Sanchez

Publications and source records attributed to M D Sanchez.

8 recordsLinked to original sources
PubMed2001

DC-SIGN interactions with human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus.

Dendritic cells (DCs) efficiently bind and transmit human immunodeficiency virus (HIV) to cocultured T cells and so may play an important role in HIV transmission. DC-SIGN, a novel C-type lectin that is expressed in DCs, has recently been shown to bind R5 HIV type 1 (HIV-1) strains and a laboratory-adapted X4 strain. To characterize the interaction of DC-SIGN with primate lentiviruses, we investigated the structural determinants of DC-SIGN required for virus binding and transmission to permissive cells. We constructed a panel of DC-SIGN mutants and established conditions which allowed comparable cell surface expression of all mutants. We found that R5, X4, and R5X4 HIV-1 isolates as well as simian immunodeficiency and HIV-2 strains bound to DC-SIGN and could be transmitted to CD4/coreceptor-positive cell types. DC-SIGN contains a single N-linked carbohydrate chain that is important for efficient cell surface expression but is not required for DC-SIGN-mediated virus binding and transmission. In contrast, C-terminal deletions removing either the lectin binding domain or the repeat region abrogated DC-SIGN function. Trypsin-EDTA treatment inhibited DC-SIGN mediated infection, indicating that virus was maintained at the surface of the DC-SIGN-expressing cells used in this study. Finally, quantitative fluorescence-activated cell sorting analysis of AU1-tagged DC-SIGN revealed that the efficiency of virus transmission was strongly affected by variations in DC-SIGN expression levels. Thus, variations in DC-SIGN expression levels on DCs could greatly affect the susceptibility of human individuals to HIV infection.

Amino Acid Sequence↗
PubMed2001

DAX-1 represses the high-density lipoprotein receptor through interaction with positive regulators sterol regulatory element-binding protein-1a and steroidogenic factor-1.

The high-density lipoprotein receptor (HDL-R) mediates the selective uptake of high-density lipoprotein cholesterol in nonplacental steroidogenic tissues. We have previously demonstrated that sterol regulatory element-binding protein-1a (SREBP-1a) and steroidogenic factor-1 (SF-1) positively regulate HDL-R gene transcription. In the present study, we examined whether DAX-1 (dosage-sensitive sex adrenal hypoplasia congenital critical region on the X chromosome, gene-1) could influence the expression of the HDL-R gene. Cotransfection studies demonstrated that DAX-1 was able to repress SREBP-1a and SF-1-dependent activation of the HDL-R promoter. Mammalian two-hybrid assays demonstrated that DAX-1 could interact with SREBP-1a. In addition, electrophoretic mobility shift assays demonstrated that initial incubation of DAX-1 with SREBP-1a protein in the absence of DNA prevented subsequent binding of SREBP-1a to the HDL-R sterol regulatory elements in a dose-dependent manner, whereas, in the case of SF-1, DAX-1 formed a complex with SF-1 protein on the DNA. These data suggest that DAX-1 inhibits SREBP-1a- and SF-1-dependent activation of the HDL-R promoter through different mechanisms. This investigation confirms that DAX-1 has an important role in regulating steroidogenesis by interfering with SREBP-1a and SF-1 induction of a gene involved in the transport of cholesterol, thereby limiting the amount of substrate available for steroid hormone production.

Amino Acid Motifs↗
PubMed2000

Autoradiographic evidence of delta-opioid receptor downregulation after prenatal stress in offspring rat brain.

In order to visualize neuroanatomical alterations in specific brain regions, light microscopy autoradiography was carried out on offsprings (postnatal day 10) from female rats stressed in different periods of gestation and controls. Group 1 was subjected to restraint stress from day 2 to 6; group 2, from day 7 to 11; group 3, from day 12 to 16; group 4 from day 2 to 16. Group 2 showed decreases in delta-opioid receptor density in different hypothalamic regions. The decrease in delta-opioid receptor density was less marked in groups 1 and 3 whereas there was no modification in group 4. Present data suggest that the prenatal stress induces a downregulation of delta-receptors in different hypothalamic regions.

Animals↗
PubMed1996

Autoradiographic evidence of mu-opioid receptors down-regulation after prenatal stress in offspring rat brain.

In order to visualize neuroanatomical alterations in specific brain regions, light microscopy autoradiography was carried out on offspring (postnatal day 10) from female rats stressed in different periods of gestation and controls. Group 1 was subjected to restraint stress from day 2 to 6; group 2, from day 7 to 11; group 3, from day 12 to 16; group 4, from day 2 to 16. Group 2 showed pronounce decreases in mu-opioid receptor density in different brain regions. The decrease in mu-opioid receptor density was less marked in the group 1, 3 and 4. Present data suggest that the prenatal stress induce down-regulation of mu-receptors in different brain regions.

Analgesics↗
PubMed1992

Prenatal stress alters the hypothalamic levels of methionine-enkephalin in pup rats.

We examined hypothalamic Methionine-enkephalin levels in offspring (postnatal day 10) from stressed female rats in different period of gestation: Group 1, restraint stress day 2 through 6; group 2, restraint stress day 7 through 11; group 3, restraint stress day 12 through day 16 and group 4, restraint stress day 2 through day 16. The hypothalamic levels of Methionine-enkephalin (134.37 +/- 6.19 pg/mg) in the offspring of stressed females from day 2 to day 6 of gestation were significantly (p < 0.001) higher than that obtained in the control group (100.66 +/- 10.13 pg/mg). Similar results were obtained in groups 2 and 3. However, in rat pups from females stressed during 15 days of gestation (group 4) the hypothalamic levels of Methionine-enkephalin (96.5 +/- 6.33 pg/mg) were similar to that obtained in the control group (101.5 +/- 5.15 pg/mg). These results suggest that acute prenatal stress alters the endogenous opioid activity in offspring with possible resultant effects on developmental processes.

Animals↗