The proposed studies will provide an in-depth ultrastructural-biochemical examination of the process by which high density lipoproteins (HDL) deliver cholesterol to mammalian cells. Specifically, we hope to identify which cells in a given organ are responsible for HDL uptake, and which aspects of the cells themselves (surface membrane sites or intracellular organelles) are involved in HDL-uptake events. Although the majority of our structurally-oriented experiments are, of necessity, directed toward tracking the protein moiety of HDL in cells, each experiment will be linked to a parallel biochemical experiment in which the relevance of a given structural event involving HDL-protein is evaluated in terms of the cell's utilization of HDL-delivered cholesterol. In addition to these efforts, we plan to test specific morphological techniques which may allow us, in the future, to directly track cholesterol in cells. In large part, we have proposed follow-up experiments on information obtained in an earlier study using the luteinized ovary as a tissue model. The planned studies can be divided into 4 major parts as follows: 1) experiments designed to retest our observation that ovarian luteal cells in vivo do not internalize HDL-protein as part of an HDL-initiated steroidogenic response; 2) experiments designed to test the observation that ovarian cells in vivo may process HDL differently than ovarian cells in vitro; 3) experiments designed to enlarge these questions regarding HDL processing to include another steroidogenic organ (adrenal) and a non-steroidogenic organ (liver); and 4) efforts to develop morphological techniques which would permit us to track the delivery of cholesterol, itself, in tissues.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL033881-01
Application #
3346191
Study Section
Metabolism Study Section (MET)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Friends Research Institute, Inc.
Department
Type
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Hu, Zhigang; Shen, Wen-Jun; Kraemer, Fredric B et al. (2017) Regulation of adrenal and ovarian steroidogenesis by miR-132. J Mol Endocrinol 59:269-283
Lin, Ye; Hou, Xiaoming; Shen, Wen-Jun et al. (2016) SNARE-Mediated Cholesterol Movement to Mitochondria Supports Steroidogenesis in Rodent Cells. Mol Endocrinol 30:234-47
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Kan, Chin Fung Kelvin; Singh, Amar Bahadur; Stafforini, Diana M et al. (2014) Arachidonic acid downregulates acyl-CoA synthetase 4 expression by promoting its ubiquitination and proteasomal degradation. J Lipid Res 55:1657-67
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Zaidi, Syed Kashif; Shen, Wen-Jun; Bittner, Stefanie et al. (2014) p38 MAPK regulates steroidogenesis through transcriptional repression of STAR gene. J Mol Endocrinol 53:1-16

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