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A Love-Hate Relationship: Cholesterol in Health and Disease >> Content Detail



Study Materials



Readings

The reading assignments listed below show what you should read before coming to class. You are expected to come to class prepared to discuss the assigned articles.


SES #TOPICSREADINGS
1Introduction
2Inborn errors of cholesterol biosynthesis

Wassif, C. A., et al. "Biochemical, Phenotypic and Neurophysiological Characterization of a Genetic Mouse Model of RSH/Smith-Lemli-Opitz Syndrome." Hum Mol Genet 10 (2001): 555-564.

Cooper, M. K., C. A. Wassif, P. A. Krakowiak, J. Taipale, R. Gong, R. I. Kelley, F. D. Porter, and P. A. Beachy. "A Defective Response to Hedgehog Signaling in Disorders of Cholesterol Biosynthesis." Nat Genet 33 (2003): 508-513.

3LDL receptor endocytosis, familial hypercholesterolemia

Brown, M. S., and J. L. Goldstein. "Familial Hypercholesterolemia: Defective Binding of Lipoproteins to Cultured Fibroblasts Associated with Impaired Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity." PNAS 71 (1974): 788-92.

Ishibashi, S., M. S. Brown, J. L. Goldstein, R. D. Gerard, R. E. Hammer, and J. Herz. "Hypercholesterolemia in Low Density Lipoprotein Receptor Knockout Mice and its Reversal by Adenovirus-mediated Gene Delivery." J Clin Invest 92 (1993): 883-893.

4Cholesterol sensing in the cells

Yang, T., P. J. Espenshade, M. E. Wright, D. Yabe, Y. Gong, R. Aebersold, J. L. Goldstein, and M. S. Brown. "Crucial Step in Cholesterol Homeostasis: Sterols Promote Binding of SCAP to INSIG-1, a Membrane Protein that Facilitates Retention of SREBPs in ER." Cell 110 (2002): 489-500.

Takaishi, K., L. Duplomb, M. Y. Wang, J. Li, and R. H. Unger. "Hepatic insig-1 or -2 Overexpression Reduces Lipogenesis in Obese Zucker Diabetic Fatty Rats and in Fasted/Refed Normal Rats." PNAS 101 (2004): 7106-7111.

5Atherosclerosis

Skalen, K., M. Gustafsson, E. K. Rydberg, L. M. Hulten, O. Wiklund, T. L. Innerarity, and J. Boren. "Subendothelial Retention of Atherogenic Lipoproteins in Early Atherosclerosis." Nature 417 (2002): 750-754.

Ricci, R., et al. "Requirement of JNK2 for Scavenger Receptor A-mediated Foam Cell Formation in Atherogenesis." Science 306 (2004): 1558-1561.

6Statins

Endo, A., M. Kuroda, K. and Tanzawa. "Competitive Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase by ML-236A and ML-236B Fungal Metabolites, having Hypocholesterolemic Activity." FEBS Lett 72 (1976): 323-326.

Istvan, E. S., and J. Deisenhofer. "Structural Mechanism for Statin Inhibition of HMG-CoA Reductase." Science 292(2001): 1160-1164.

7Cholesterol absorption inhibitors

Van Heek, M., C. F. France, D. S. Compton, R. L. McLeod, N. P. Yumibe, K. B. Alton, E. J. Sybertz, and H. R. Davis Jr. "In vivo Metabolism-based Discovery of a Potent Cholesterol Absorption Inhibitor, SCH58235, in the Rat and Rhesus Monkey through the Identification of the Active Metabolites of SCH48461." J Pharmacol Exp Ther 283 (1997): 157-163.

Altmann, S. W., et al. "Niemann-Pick C1 Like 1 Protein is Critical for Intestinal Cholesterol Absorption." Science 303 (2004): 1201-1204.

8Atherosclerosis and heart attack, current treatmentsNo papers to read. We will be going on a field trip to Beth-Israel Deaconess Medical Center today.
9ABCA1, Tangier disease

Rust, S., M. Rosier, H. Funke, J. Real, Z. Amoura, J. C. Piette, J. F. Deleuze, H. B. Brewer, N. Duverger, P. Denefle, and G. Assmann. "Tangier Disease is Caused by Mutations in the Gene Encoding ATP-binding Cassette Transporter 1." Nat Genet 4 (1999): 352-355.

McNeish, J., et al. "High Density Lipoprotein Deficiency and Foam Cell Accumulation in Mice with Targeted Disruption of ATP-binding Cassette Transporter-1." PNAS 97 (2000): 4245-4250.

10Increasing HDL, fibrates, diet

Mardones, P., et al. "Fibrates Down-regulate Hepatic Scavenger Receptor Class B Type I Protein Expression in Mice." J Biol Chem 278 (2003): 7884-7890.

Williams, P. T., P. J. Blanche, R. Rawlings, and R. M. Krauss. "Concordant Lipoprotein and Weight Responses to Dietary Fat Change in Identical Twins." Am J Clin Nutr 82 (2005): 181-187.

11Cholesterol in the brain, Alzheimer's disease

Mauch, D. H., K. Nagler, S. Schumacher, C. Goritz, E. C. Muller, A. Otto, and F. W. Pfrieger. "CNS Synaptogenesis Promoted by Glia-derived Cholesterol." Science 294, no. 5545 (2001): 1354-1357.

Howland, D. S., et al. "Modulation of Secreted Beta-amyloid Precursor Protein and Amyloid Beta-peptide in Brain by Cholesterol." J Biol Chem 273 (1998): 16576-16582.

12Future of drug therapies

Lum, P. Y., et al. "Discovering Modes of Action for Therapeutic Compounds using a Genome-wide Screen of Yeast Heterozygotes." Cell 116 (2004): 121-137.

Gagne, C., D. Gaudet, and E. Bruckert for the Ezetimibe Study Group. "Efficacy and Safety of Ezetimibe Coadministered with Atorvastatin or Simvastatin in Patients with Homozygous Familial Hypercholesterolemia." Circulation 105 (2002): 2469-2475.

13Discussion of assignment 2

 








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