Spelling suggestions: "subject:"cholesterol,"" "subject:"eholesterol,""
121 |
The intracellular control of cholesterol metabolismSampson, William James January 1988 (has links)
The liver has a major role in the metabolism of cholesterol, being the main site of lipoprotein assembly and degradation and the only tissue where the metabolism of cholesterol to bile acids occurs. This provides the major pathway for the removal of cholesterol from the body. The results described in this thesis concern the use of specific enzyme inhibitors (58-035, Azacholesterol, Mevinolin) to determine the intracellular use of different sources of cholesterol in monolayers of rat hepatocytes. In particular, the fates of newly synthesized cholesterol from mevalonic acid and cholesterol derived from HDL2 were investigated. Incubation of hepatocyte monolayers with 58-035 resulted in the inhibition of esterification. In the presence of mevalonic acid as a cholesterol source, 58-035 stimulated bile acid synthesis. Azacholesterol inhibited bile acid synthesis, had no effect on cholesterol synthesis, and in the presence of mevalonic acid, stimulated secretion of cholesterol by the hepatocytes; it had no effect on cholesterol esterification. Mevinolin inhibited cholesterol synthesis and as a result inhibited esterification. HDL2, in the presence of mevinolin, was used as a cholesterol source. It stimulated bile acid synthesis and cholesterol esterification. Addition of 58-035 to the system resulted in the inhibition of both esterification and bile acid synthesis. Overall, the results indicated that different intracllular pools of free cholesterol exist and that the inter-relationships of these pools give a complex pattern of flux of intracellular cholesterol between various pathways in the rat hepatocyte.
|
122 |
The role of apolipoprotein E in gallstone disease, colorectal cancer and gastrointestinal cell regulationNiemi, M. (Mari) 11 January 2000 (has links)
Abstract
Apolipoprotein E (apo E) is one of the key regulatory proteins in cholesterol
and lipoprotein metabolism. The present research focuses on the role of apo E in
gastrointestinal diseases. The polymorphism of apo E has been suggested to be
associated with the cholesterol content in gallstones and the crystallization
rate of gallbladder bile. The possible effect of apo E polymorphism on the
susceptibility to gallstone disease at the population level was examined in
comparison with the classical risk factors for gallstone disease. The data
suggest that the apolipoprotein E2 isoform is a genetic factor that provides
protection against gallstone disease in women.
The alterations in plasma lipoprotein levels and bile acid
metabolism observed in patients with colorectal adenoma and carcinoma may
reflect a genetic background predisposing to tumors through altered lipid
metabolism. To determine, whether the polymorphism of apo E is associated with
proximal or distal colonic neoplasia, the apo E phenotype was determined in 135
patients with colorectal carcinoma, and 199 randomly selected control subjects.
The frequency of the ε4 allele of apo E was low in the patients with
proximal
adenoma and those with carcinoma, respectively, compared with the control
subjects. The patients with distal tumors showed no alteration in ε4
frequency.
The data suggest that the ε4 allele of apo E provides protection against
the
development of adenoma and carcinoma of the proximal colon. The association of
apo E polymorphism with tumors is not a generalized phenomenon as is shown by
the lack of association with breast or prostate cancers.
To further study the mechanisms by which apo E might affect colon cancer, the
expression of apo E in human intestine and the localization of apo E in normal
and malignant gastrointestinal tract was studied using immunohistochemistry and
in situ hybridization. Both immunoreactive apo E protein
and apo E mRNA were present throughout the stomach, small intestine and colon.
The phagocytes of lamina propria were positive for apo E, but the number of
positive cells and the staining intensity varied according to localization.
Macrophages in the superficial lamina propria of normal colon were more strongly
positive for apo E than those in the small intestine, where the most positively
stained cells were dendritic cells and macrophages in the germinal centers of
lymphoid follicles. In samples from colorectal carcinomas intensely positive
macrophages surrounded the tumor area, suggesting that apo E might play a role
in the proliferation of malignant cells.
Apo E binds with very high affinity to heparin and proteoglycans and inhibits
the proliferation of several cell types, but the antiproliferative mechanism of
apo E is still largely unknown. The effects of apo E at the cellular levels were
studied in cell culture experiments. The effect of recombinant human apo E3 on
cell polarity and the distribution of β-catenin were examined in
undifferentiated (G+) and differentiated (G+ reversed) HT29 human colon
adenocarcinoma cell lines. In cultured undifferentiated HT29 cells, treatment
with apo E improved cell polarity and translocated β-catenin from the
cytoplasm
to cell-cell adhesion sites. Apo E may thus modulate epithelial integrity and
contribute to cell growth and malignant transformation.
|
123 |
Asociation of PCSK9 with Low Density Lipoproteins (LDL) in the Regulation of LDL-Cholesterol LevelsSarkar, Samantha Khadija January 2015 (has links)
Proprotein Convertase Subtilisin / Kexin Type-9 (PCSK9) has emerged as a major regulator of plasma cholesterol levels. PCSK9 is secreted mainly from the liver and circulates as a plasma protein. PCSK9 binds cell surface low-density lipoprotein (LDL) receptors and mediates their degradation upon endocytosis in the liver. This decreases the liver’s ability to clear LDL-cholesterol from the blood. PCSK9 is also capable of binding LDL particles themselves; this interaction inhibits the ability of PCSK9 to bind and mediate LDLR degradation in cultured hepatic cells, but its effect on PCSK9 function in vivo remains unknown. A disordered N-terminal region of the PCSK9 prodomain is necessary for binding to isolated LDL particles in vitro. This N-terminal region is also autoinhibitory to PCSK9-LDL receptor binding. We hypothesized that the N-terminal of the PCSK9 prodomain plays a role in an allosteric mechanism that regulates PCSK9 function. Through mutagenesis studies, we found that both a conserved stretch of acidic residues and an adjacent conserved stretch of hydrophobic residues are crucial for the PCSK9-LDL interaction; the hydrophobicity of the residue at position 38 (Tyr) within the conserved acidic stretch was also found to be important for this. Helical wheel modeling of the prodomain N-terminal sequence revealed the potential for a lipid-ordered amphipathic helix to form, which may aid PCSK9 docking onto LDL. Replacing residues A44 and L41 with helix-disrupting proline residues abolished LDL binding. Co-pelleting ultracentrifugation assays also show that wild-type PCSK9 is capable of associating with liposomes, while the A44P mutation disrupts this lipid association. The A44P-PCSK9 mutation, showing an 80-90% decrease in LDL association but with LDL receptor binding and degrading functions intact, may serve as an important tool in future studies investigating the PCSK9-LDL interaction in vivo. Elucidation of the mechanism by which LDL-binding naturally inhibits PCSK9 activity may also help to develop new anti-PCSK9 therapeutics in the future.
|
124 |
The effect of thiocholesterol on the acute toxicity of mercuric chlorideBurgun, James J. January 1977 (has links)
This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).
|
125 |
Dietary cholesterol on free and bound cholesterol and lipid-phosphorus content of rabbit and rat aorta, heart muscle, plasma and adrenal /Constantine, Jay Winfred January 1959 (has links)
No description available.
|
126 |
Hypocholesterolemic mechanisms of dihydrocapsaisin /Noel, Steven Alan January 1987 (has links)
No description available.
|
127 |
Studies on the effect of dietary factors and drugs on cholesterol metabolism in the hen /Weiss, Joseph Francis January 1966 (has links)
No description available.
|
128 |
Effect of certain compounds on sterol metabolism of laying hens /Singh, Ram Awadh,1942- January 1970 (has links)
No description available.
|
129 |
The interrelationship between hepatic microsomal cholesterol 7[alpha]-hydroxylase and mixed function oxidase systems /Mellon, William Sawyer January 1977 (has links)
No description available.
|
130 |
Amperometric enzymatic determination of total cholesterol in serum using tubular carbon electrodes /Hahn, Younghee January 1977 (has links)
No description available.
|
Page generated in 0.1487 seconds