Abcg5 And Abcg8 Promote Neutral Sterol Excretion Into Bile

The specific defects in sterol transport observed in sitosterolemic patients indicate that ABCG5 and ABCG8 facilitate the excretion of sterols from the liver and intestine. To test this hypothesis, we developed P1 transgenic mice expressing human ABCG5 and ABCG8 (Yu et al. 2002). The transgenes were expressed primarily in the liver and small intestine, mirroring the tissue distribution of expression of the endogenous genes. Transgene expression had only modest effects on plasma and liver...

References

AbdAlla S., Lother H., Abdel-tawab A.M., and Quitterer U. 2001. The angiotensin II AT2 receptor is an AT1 receptor antagonist. J. Biol. Chem. 276 39721. Agerholm-Larsen B., Nordestgaard B.G., Steffensen R., Sorensen T.I., Jensen G., and Tybjaerg-Hansen A. 1997. ACE gene polymorphism Ischemic heart disease and longevity in 10,150 individuals. A case-reference and restrospective cohort study based on the Copenhagen City Heart Study. Circulation 95 2358. Asano K., Dutcher D.L., Port J.D., Minobe...

Symposium Participants

Abman, Steven, Dept. of Pediatrics, The Children's Hospital, University of Colorado, Denver Acevedo-Bolton, Gabriel, Dept. of Bioengineering, California Institute of Technology, Pasadena, California Albrecht, Barbara, PH-R CVII, Bayer AG, Wuppertal, Germany Alitalo, Kari, Lab. of Molecular and Cancer Biology, University of Helsinki, Helsinki, Finland Allen, Claire, Developmental Genetics Programme, Biomedical Science, University of Sheffield, Sheffield, United Kingdom Ap tel, Herve, Dept. of...

Vascular Endothelial Growth Factor Acts Upstream Of Notch

What acts upstream of Notch Recent studies in ze-brafish and mice have revealed a surprising new role for vascular endothelial growth factor (VEGF) signaling upstream of Notch. VEGF-A is a key regulator of vascular development in vertebrates (Ferrara and Gerber 2001). It mediates vascular permeability and functions as an en-dothelial mitogen and angiogenic inducer. Loss of only a single allele of this gene is lethal in mouse, with severe defects in both vasculogenic and angiogenic blood vessel...

Sitosterolemia Is A Disorder Of Neutral Sterol Trafficking

Defects in LDLR function are the primary cause of three of the four Mendelian forms of severe hypercholes-terolemia. The fourth form, sitosterolemia, is a more generalized disorder of neutral sterol transport (Bjorkhem et al. 2001) that is distinguished from the other monogenic forms of hypercholesterolemia in three important aspects. First, patients with sitosterolemia have markedly increased concentrations of plant sterols, as well as animal-derived sterols, in their blood and body tissues...

RJ Roman AW Cowley Jr A Greene AE Kwitek PJ Tonellato and HJ Jacob

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53005 The next step following completion of the first draft of the sequence of the human genome is to overlay this information with a complementary functional genomic map of the location of disease-causing genes and those involved in the regulation of normal function. To this end, our group has been developing two chromosomal substitution panels of 44 strains of consomic rats in which one chromosome at a time from a...

Arh Is Required For Ldlr Internalization

The specific role of ARH in LDLR endocytosis has not been fully defined. Norman et al. (1999) reported that lymphocytes from two patients with a clinical phenotype consistent with ARH had increased cell-surface binding but markedly reduced internalization of LDL. Treatment of the cells with pronase indicated that almost all of the LDLRs were on the plasma membrane. These data suggest that ARH is not required for trafficking of the LDLR to the cell surface, nor for the binding of LDL to the...

Regulation Of Srebp Isoform Expression

Plasma Fplc

SREBP expression is determined by posttranscrip-tional regulatory mechanisms that alter SREBP cleavage and by mechanisms that regulate gene transcription. Post-transcriptional regulation involves sterol-mediated suppression of SREBP cleavage, which occurs by inhibiting the movement of the SCAP SREBP complex from the ER to the Golgi apparatus (Fig. 1). This form of regulation blocks all SREBP isoform precursor cleavage in cells cultured in the presence of sterols (Goldstein et al. 2002) and in...

The Fetalto Adult Energy Metabolic Switch Postnatal Induction of Cellular Mitochondrial Energy Transduction Production

Following birth, the heart undergoes a remarkable metabolic maturation such that the normal adult myocardium is capable of high-capacity utilization of both glucose and fatty acids for ATP production (Bing 1955 Neely et al. 1972 Warshaw 1972). During the fetal stages, the heart relies mainly on glucose for energy. Following birth, the increased hemodynamic demands imposed on the left ventricle, which serves as a constant pump throughout the life of the organism, mandates a reliable,...

R Benezra P de Candia H Li E Romero D Lyden S Rafii and M Ruzinova

*Department of Cell Biology and fDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 fDepartment of Medicine-Hematology Oncology, New York Medical Center, New York, New York 10021 There is a widely held belief in the field of cancer biology, proposed originally by Dr. Judah Folkman, that tumors cannot grow beyond a very limited size if the mi-crovessel density within the tumor is sufficiently low. Therefore, inhibition of the formation of blood vessels...

In Vivo Experiments

To determine whether endogenous uric acid plays an important role in preventing inactivation of Cu ZnSODs by H2O2 in vivo, we examined the effect of increased uric acid on SOD activity in aortas from atherosclerotic vessels in ApoE- - mice, in which superoxide production is increased. To increase endogenous levels of uric acid in these mice, oxonic acid was infused. Oxonic acid is a potent inhibitor of uricase and is the enzyme responsible for catalyzing the reaction of uric acid to allantoin...