'One of the major oxysterols in the human circulation is 4 beta-hydroxycholesterol formed from cholesterol by the drug-metabolizing enzyme cytochrome P450 3A4. Deuterium-labeled 4 beta-hydroxycholesterol was injected into two healthy volunteers, and the apparent half-life was found to be 64 and 60 h, respectively. We have determined earlier the half-lives ... More
Activation of retinoic acid receptor-dependent transcription by all-trans-retinoic acid metabolites and isomers.
Authors Idres Nadia; Marill Julie; Flexor Maria A; Chabot Guy G;
JournalJ Biol Chem
PubMed ID12070176
'We have shown that four metabolites of all-trans-retinoic acid (ATRA) (4-oxo-, 4-OH-, 18-OH-, and 5,6-epoxy-RA) can induce maturation of NB4 promyelocytic leukemia cells (Idres, N., Benoit, G., Flexor, M. A., Lanotte, M., and Chabot, G. G. (2001) Cancer Res. 61, 700-705). To better understand the mechanism of action of ATRA ... More
Inhibition of transforming growth factor beta signaling and Smad-dependent activation of transcription by the Latent Membrane Protein 1 of Epstein-Barr virus.
'Inhibition of transforming growth factor beta (TGFbeta) signaling by the Epstein-Barr virus Latent Membrane Protein 1 (LMP1) may account, at least in part, for the oncogenic activity of LMP1. We found that LMP1 is a potent inhibitor of TGFbeta signaling and Smad-dependent activation of transcription in 293 epithelial cells and ... More
Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins.
AuthorsLamark T, Perander M, Outzen H, Kristiansen K, Øvervatn A, Michaelsen E, Bjørkøy G, Johansen T,
JournalJ Biol Chem
PubMed ID12813044
'The Phox and Bem1p (PB1) domain constitutes a recently recognized protein-protein interaction domain found in the atypical protein kinase C (aPKC) isoenzymes, lambda/iota- and zeta PKC; members of mitogen-activated protein kinase (MAPK) modules like MEK5, MEKK2, and MEKK3; and in several scaffold proteins involved in cellular signaling. Among the last ... More
Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating.
Authors Sobolevsky Alexander I; Beck Christine; Wollmuth Lonnie P;
JournalNeuron
PubMed ID11779481
Many N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. ... More
Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1.
Authors Wong Wai K; Ou Xiao-Ming; Chen Kevin; Shih Jean C;
JournalJ Biol Chem
PubMed ID11956220
Monoamine oxidases (MAO) A and B deaminate a number of biogenic amines. Aberrant expression of MAO is implicated in several psychiatric and neurogenerative disorders. In this study, we have shown that phorbol 12-myristate 13-acetate (PMA) increases human MAO B, but not MAO A, gene expression. The sequence between -246 and ... More
Specific inhibition of ICAM-1 expression mediated by gene targeting with Triplex-forming oligonucleotides.
AuthorsBesch R, Giovannangeli C, Kammerbauer C, Degitz K
JournalJ Biol Chem
PubMed ID12080053
Selected sequences in the DNA double helix can be specifically recognized by oligonucleotides via hydrogen bonding interactions. The resulting triple helix can modulate DNA metabolism and especially interfere with transcription in a gene-specific manner. To explore the potential of triplex-forming oligonucleotides (TFOs) as gene repressors, a TFO was designed to ... More
Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival.
Authors Sotiriou Sotiria; Gispert Suzana; Cheng Jun; Wang Yaohui; Chen Amy; Hoogstraten-Miller Shelley; Miller Georgina F; Kwon Oran; Levine Mark; Guttentag Susan H; Nussbaum Robert L;
JournalNat Med
PubMed ID11984580
The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, ... More
Cholesterol modulates the membrane binding and intracellular distribution of annexin 6.
Authors de Diego Iñaki; Schwartz Felix; Siegfried Heide; Dauterstedt Paul; Heeren Joerg; Beisiegel Ulrike; Enrich Carlos; Grewal Thomas;
JournalJ Biol Chem
PubMed ID12070178
Annexins are Ca(2+)- and phospholipid-binding proteins that are widely expressed in mammalian tissues and that bind to different cellular membranes. In recent years its role in membrane traffic has emerged as one of its predominant functions, but the regulation of its intracellular distribution still remains unclear. We demonstrated that annexin ... More
Regulation of calreticulin expression during induction of differentiation in human myeloid cells. Evidence for remodeling of the endoplasmic reticulum.
Authors Clark Robert A; Li Sen-Lin; Pearson Doran W; Leidal Kevin G; Clark Joshua R; Denning Gerene M; Reddick Robert; Krause Karl-Heinz; Valente Anthony J;
JournalJ Biol Chem
PubMed ID12065601
Induction of differentiation of HL-60 human myeloid cells profoundly affected expression of calreticulin, a Ca(2+)-binding endoplasmic reticulum chaperone. Induction with Me(2)SO or retinoic acid reduced levels of calreticulin protein by approximately 60% within 4 days. Pulse-chase studies indicated that labeled calreticulin decayed at similar rates in differentiated and undifferentiated cells ... More
Elucidation of structure and biological properties of the prion protein scrapie (PrP(Sc)) is fundamental to an understanding of the mechanism of conformational transition of cellular (PrP(C)) into disease-specific isoforms and the pathogenesis of prion diseases. Unfortunately, the insolubility and heterogeneity of PrP(Sc) have limited these studies. The observation that a ... More
Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways.
Authors Eto Masato; Kozai Toshiyuki; Cosentino Francesco; Joch Hana; Lüscher Thomas F;
JournalCirculation
PubMed ID11956113
BACKGROUND: Tissue factor plays a pivotal role in thrombus formation in acute coronary syndromes. However, the regulatory mechanisms underlying tissue factor expression are poorly understood. Statins are effective in patients with acute coronary syndromes. Hence, the aim of this study was to clarify in human endothelial cells the signaling pathways ... More
Malignant effusions and immunogenic tumour-derived exosomes.
BACKGROUND: Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with ... More
Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects.
Authors Ho Ling-Pei; Davis Margaret; Denison Alan; Wood Fraser T; Greening Andrew P;
JournalChest
PubMed ID12006423
STUDY OBJECTIVES: To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis. SETTING: University teaching hospital. Patients and methods: IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with ... More