PubMed Health⌕ Search

Biomedical subjects

J Beers

Publications and source records attributed to J Beers.

8 recordsLinked to original sources
PubMed2001

The apolipoprotein E-dependent low density lipoprotein cholesteryl ester selective uptake pathway in murine adrenocortical cells involves chondroitin sulfate proteoglycans and an alpha 2-macroglobulin receptor.

Cells acquire lipoprotein cholesterol by receptor-mediated endocytosis and selective uptake pathways. In the latter case, lipoprotein cholesteryl ester (CE) is transferred to the plasma membrane without endocytosis and degradation of the lipoprotein particle. Previous studies with Y1/E/tet/2/3 murine adrenocortical cells that were engineered to express apolipoprotein (apo) E demonstrated that apoE expression enhances low density lipoprotein (LDL) CE uptake by both selective and endocytic pathways. The present experiments test the hypothesis that apoE-dependent LDL CE selective uptake is mediated by scavenger receptor, class B, type I (SR-BI). Surprisingly, SR-BI expression was not detected in the Y1/E/tet/2/3 clone of Y1 adrenocortical cells, indicating the presence of a distinct apoE-dependent pathway for LDL CE selective uptake. ApoE-dependent LDL CE selective uptake in Y1/E/tet/2/3 cells was inhibited by receptor-associated protein and by activated alpha(2)-macroglobulin (alpha(2)M), suggesting the participation of the LDL receptor-related protein/alpha(2)M receptor. Reagents that inhibited proteoglycan synthesis or removed cell surface chondroitin sulfate proteoglycan completely blocked apoE-dependent LDL CE selective uptake. None of these reagents inhibited SR-BI-mediated LDL CE selective uptake in the Y1-BS1 clone of Y1 cells in which LDL CE selective uptake is mediated by SR-BI. We conclude that LDL CE selective uptake in adrenocortical cells occurs via SR-BI-independent and SR-BI-dependent pathways. The SR-BI-independent pathway is an apoE-dependent process that involves both chondroitin sulfate proteoglycans and an alpha(2)M receptor.

Adrenal Cortex↗
PubMed2001

Preferential incorporation of glucosamine into the galactosamine moieties of chondroitin sulfates in articular cartilage explants.

OBJECTIVE: To determine the metabolic fate of glucosamine (GlcN) in intact articular cartilage tissue. METHODS: Intact articular cartilage explants were cultured for up to 13 days in Dulbecco's modified Eagle's medium supplemented with 1) 1-13C-labeled GlcN, 2) 1-13C-labeled glucose (Glc), or 3) no labeling. Every 3-4 days, samples were removed and frozen in liquid nitrogen for carbon-13 magnetic resonance spectroscopic (MRS) analysis. The metabolic products of the labeled precursors were determined from the MRS data based on resonance positions and comparison with known standards and published values. RESULTS: GlcN was taken up by the chondrocytes and incorporated selectively into the hexosamine, but not the hexuronic acid, components of the glycosaminoglycan chains of articular cartilage proteoglycan. The data also demonstrated that GlcN is the substrate of choice for the galactosamine moieties of the chondroitin sulfates, incorporating at levels 300% higher than with an equivalent amount of labeled Glc. CONCLUSION: The results indicate that GlcN facilitates the production of proteoglycan components that are synthesized through the hexosamine biochemical pathway.

Animals↗
PubMed2000

Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimer's disease.

Beta-amyloid peptide (Abeta), which plays a central role in the pathogenesis of Alzheimer's disease, is derived from the transmembrane beta-amyloid precursor protein (APP) by proteolytic processing. Although mechanisms associated with Abeta generation are not fully understood, it is known that Abeta can be generated within endosomal compartments upon internalization of APP from the cell surface. The low density lipoprotein receptor-related protein (LRP) was previously shown to mediate the endocytosis of APP isoforms containing the Kunitz proteinase inhibitor domain (Kounnas, M. Z., Moir, R. D., Rebeck, G. W., Bush, A. I., Argraves, W. S., Tanzi, R. E., Hyman, B. T., and Strickland, D. K. (1995) Cell 82, 331-340; Knauer, M. F., Orlando, R. A., and Glabe, C. G. (1996) Brain Res. 740, 6-14). The objective of the current study was to test the hypothesis that LRP-mediated internalization of cell surface APP can modulate APP processing and thereby affect Abeta generation. Here, we show that long term culturing of cells in the presence of the LRP-antagonist RAP leads to increased cell surface levels of APP and a significant reduction in Abeta synthesis. Further, restoring LRP function in LRP-deficient cells results in a substantial increase in Abeta production. These findings demonstrate that LRP contributes to Abeta generation and suggest novel pharmacological approaches to reduce Abeta levels based on selective LRP blockade.

Alzheimer Disease↗
PubMed2000

Sensitivity of MRI to proteoglycan depletion in cartilage: comparison of sodium and proton MRI.

OBJECTIVE: The purpose of this work was to evaluate the results from sodium and proton magnetic resonance imaging (MRI) in detecting small changes in proteoglycan (PG) content in bovine articular cartilage specimens. DESIGN: Articular cartilage from 15 specimens of bovine patellae were subjected to partial PG depletion with different concentrations of trypsin for 30 min. Sodium and proton MR images of the intact specimen were obtained on a 4T GE clinical MRI system. Two custom-built 7 cm-diameter solenoid coils tuned to proton and sodium frequencies were employed. Fast gradient echo and spin echo imaging sequences were used to determine sodium density, proton density and proton relaxation times (T(1)and T(2)) of the specimens. Spectrophotometric assay was performed after MRI to determine PG concentrations of the cartilage specimens. RESULTS: The sodium signal change correlated well with the observed PG loss (R(2)=0.85, P< 0.01) whereas the proton signal change was inconsistent (R(2)=0.10, P< 0.8). The change in proton T(1)and T(2)between the two regions did not correlate with PG loss (R(2)=0. 07 and R(2)=0.06, respectively). CONCLUSIONS: Results from these studies demonstrate that sodium MRI is both sensitive and specific in detecting small changes in PG concentration, whereas proton density and relaxation properties are not sensitive to small changes in PG content.

Animals↗
PubMed1997

Purification, characterization, and localization of yeast Cox17p, a mitochondrial copper shuttle.

Cox17p was previously shown to be essential for the expression of cytochrome oxidase in Saccharomyces cerevisiae. In the present study COX17 has been placed under the control of the GAL10 promoter in an autonomously replicating plasmid. A yeast transformant harboring the high copy construct was used to purify Cox17p to homogeneity. Purified Cox17p contains 0.2-0.3 mol of copper per mol of protein. The molar copper content is increased to 1.8 after incubation of Cox17p in the presence of a 6-fold molar excess of cuprous chloride under reduced conditions. An antibody against Cox17p was obtained by immunization of rabbits with a carboxyl-terminal peptide coupled to bovine serum albumin. The antiserum detects Cox17p in both the mitochondrial and soluble protein fractions of wild type yeast and of the transformant overexpressing Cox17p. Exposure of intact mitochondria to hypotonic conditions causes most of Cox17p to be released as a soluble protein indicating that the mitochondrial fraction of Cox17p is localized in the intermembrane space. These results are consistent with the previously proposed function of Cox17p, namely in providing cytoplasmic copper for mitochondrial utilization.

Amino Acid Sequence↗
PubMed1997

Lipid composition changes in normal breast throughout the menstrual cycle.

The detection of breast cancer in women using magnetic resonance imaging (MRI) is increasingly used as a supplement to X-ray mammography. Furthermore, proton MR spectroscopy (1H MRS) has detected alterations in lipid profiles that are linked with tumor development and progression in human biopsy tissue. Because normal "resting" breast is highly active, it is necessary to consider that any alterations observed in lipid profiles may not be indicative of breast tumor development. The purpose of this study was to assess the changes in lipid composition in the breast throughout the menstrual cycle in "normals" using MRS at 4.0 T. Five women with no known history of breast disease were subject to biweekly MRS breast examinations. MRS results showing water and fat resonances revealed cyclic changes in the lipid content throughout the duration of the menstrual cycle. In particular, intensity changes were seen in methylene (-CH2-) and allylic methylene (CH2CH2*CH=) resonances at 2.1 ppm and 1.3 ppm, respectively. These intensity changes assumed a similar cyclic trend for each subject over the 28 days that correlate with the follicular, ovulatory, and luteal phases of the menstrual cycle. The results obtained may indicate cell synthesis or metabolic activity in the breast during the menstrual cycle and provide valuable information pertinent to lipid responses associated with breast disease.

Adult↗