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HPMR

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apolipoprotein A1 OKDB#: 3504
 Symbols: APOA1 Species: human
 Synonyms: HPALP2, apo(a)  Locus: 11q23.3 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment NCBI Summary: This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]
General function Extracellular binding protein
Comment LDL species heterogeneity in the atherogenic dyslipidemia of polycystic ovary syndrome. Doi SA et al. (2008) One of the important risk factors for coronary heart disease is dyslipidemia. Several lipid abnormalities have been studied in patients with polycystic ovary syndrome (PCOS), but the relationship between PCOS and low-density lipoprotein (LDL) subclass pattern is not clear. A case-control study was designed to look into lipid differences, and LDL size was analyzed by a newly developed polyacrylamide tube gel electrophoresis method. Results indicated that only PCOS status and serum triglyceride levels were independently associated with LDL particle size. The apolipoprotein (Apo)A-I level was higher in PCOS patients with small dense LDL (sdLDL). PCOS seems to result in smaller LDL particle size and higher ApoA-I levels independent of triglyceride levels. After adjusting for triglyceride levels, other traits of insulin resistance syndrome (IRS) were not associated with LDL size phenotype, suggesting that the IRS-related sdLDL is linked most strongly to alterations in triglyceride levels.//////////////////
Cellular localization Secreted
Comment candidate123
Ovarian function Steroid metabolism, Luteolysis
Comment The apolipoprotein A-I level is downregulated in the granulosa cells of patients with polycystic ovary syndrome and affects steroidogenesis. Choi DH 2010 et al. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder found in women. The etiology of PCOS is still not clear, and there are no available studies on the proteome analysis of granulosa cells (GCs) in PCOS patients. To identify the pathogenic mechanisms and potential diagnostic markers for PCOS, we conducted proteomic profiling of GCs in PCOS patients by two-dimensional gel electrophoresis and liquid chromatography coupled with mass spectrometry (LC-MS/MS) analyses. The proteomic analysis yielded eight downregulated and 12 upregulated proteins in PCOS patients, among which apolipoprotein A-I (ApoA-I) showed significant downregulation in PCOS patients as confirmed by Western blotting. Knockdown of ApoA-I decreased the number of transcripts of steroidogenic enzymes in a granulosa cell line (KGN), while its overexpression generally increased the level of expression of these enzymes. Furthermore, modulation of the expression level of ApoA-I in the granulosa cells altered progesterone production. Therefore, this study suggests that ApoA-I can be useful as a granulosa cell biomarker of PCOS patients and that downregulated ApoA-I may be related to the disturbed production of steroid hormones in PCOS patients. ///////////////////////// The Reverse Cholesterol Transport System as a Potential Mediator of Luteolysis in the Primate Corpus Luteum. Bogan R et al. The cessation of progesterone (P4) production (i.e., functional regression), arguably the key event in luteolysis of the primate corpus luteum (CL), is poorly understood. Previously, we found that genes encoding proteins involved in cholesterol uptake decreased while those involved in cholesterol efflux (reverse cholesterol transport; RCT) increased in expression during spontaneous functional regression of the rhesus macaque CL, thereby potentially depleting the cholesterol reserves needed for steroidogenesis. Therefore, a comprehensive analysis of the components necessary for RCT was performed. RCT components were expressed (mRNA and/or protein) in the macaque CL including cholesterol sensors (liver x receptors alpha or NR1H3; and beta or NR1H2), efflux proteins (ATP-binding cassette subfamilies A1 or ABCA1; and G1 or ABCG1), acceptors (apolipoproteins A1 or APOA1; and E or APOE), and plasma proteins facilitating high-density lipoprotein (HDL) formation (lecithin:cholesterol acyltransferase or LCAT; phospholipid transfer protein or PLTP). ABCA1, APOE, PLTP and NR1H3 increased, while lipoprotein receptors decreased, in expression (mRNA and/or protein) through the period of functional regression. The expression of APOA1 and APOE, as well as NR1H3, was greatest in the CL and tissues involved in regulating cholesterol homeostasis. Immunolocalization studies revealed that RCT proteins and lipoprotein receptors were expressed in large luteal cells, which possess intracellular cholesterol reserves during periods of progesterone synthesis. Lipid staining revealed changes in luteal cholesterol ester/lipid distribution that occurred following functional regression. These results indicate that decreased cholesterol uptake and increased RCT may be critical for the initiation of primate luteolysis by limiting intracellular cholesterol pools required for steroidogenesis.
Expression regulated by LH, Steroids
Comment Progesterone Receptor-Induced Gene Expression in Primary Mouse Granulosa Cell Cultures. Sriraman V et al. The progesterone receptor (PGR) is induced by LH in granulosa cells of preovulatory follicles and the PGR-A isoform is essential for ovulation based on the phenotypes of Pgr isoform specific knockout mice. Although several genes regulated by PGR-A in vivo have been identified, whether these genes are primary targets of PGR-A or if their expression also depends on other signaling molecules that are induced by the LH surge have not been resolved. Therefore, to identify genes that are either induced or repressed by PGR in the absence of LH mediated signaling cascades, we infected primary cultures of mouse granulosa cells with either PGR-A or PGR-B adenoviral vectors without or with R5020 as a PGR ligand. Total RNA was extracted from infected cells at 16 h and analyzed by Affymetrix Mouse 430 2.0 microarrays. PGR-A in the presence or absence of ligand significantly induced ~50 genes 2-fold or more (LPE test at P-value <= 0.01). Fewer and different genes were induced by PGR-B in the absence of ligand. Edn1, Apoa1 and Cited1 were primarily regulated by PGR-A as verified by additional RT-PCR analyses, suppression by the PGR antagonist RU486 and by the lack of induction by protein kinase A, protein kinase C or EGF-like factors pathways. PGR regulation of these genes was confirmed further by gene expression analyses in hormonally-primed Pgr mutant mouse ovaries. Because Edn1, Apoa1 and Cited1 are known to regulate angiogenesis, PGR may impact the neovascularization of follicles that is initiated with ovulation.
Ovarian localization Granulosa
Comment Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.
Follicle stages
Comment
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 1 mutations

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Dyslipidemia with particular regard to apolipoprotein profile in association with polycystic ovary syndrome: a study among Indian women. Maitra A et al. (2001) To investigate putative dyslipidemia in women with polycystic ovary syndrome (PCOS) with particular emphasis on specific parameters of atherosclerotic risk, and to assess the independent influence of obesity and hyperandrogenemia on these parameters. Women investigated were among those attending the infertility clinics. Three groups of women were studied: (I) a core study group consisting of oligomenorrhoeic, chronically anovulatory women with or without obesity in whom polycystic ovaries were confirmed through ultrasound evidence, and were established to be the cause of infertility; II) a control group of non-hirsute, non-obese women with regular menstrual cycles; and (III) a group of controls consisting of women with obesity, but with normal ovarian morphology and regular menstrual cycles. All three study groups were investigated for androgen (total testosterone) and lipid-lipoprotein profile, including apolipoproteins, ApoA1 and ApoB. Retrospective analysis of the data was carried out to assess hyperandrogenism in the study group of women with PCOS as well as to investigate changes in the lipid-lipoprotein profile, particularly the measures of cardiovascular risk, ApoA1 and ApoB. Triglycerides showed a significant increase in the PCOS group compared to controls, whereas HDL-cholesterol as well as HDL-carrying ApoA1 showed a significant decrease (P < .05). Also a significant finding was the decrease in ApoA1/ApoB ratio among the women with PCOS compared to both controls and obese women. A direct negative correlation of this decrease in ApoA1/ApoB ratio with the Body Mass Index was also confirmed in the study. Hyperandrogenemia in terms of significantly raised total testosterone levels was found in 30% of the PCOS women. However, no direct correlation of this increase with changes in lipid-lipoprotein profile could be observed. The study confirms the trend toward dyslipidemia among women with PCOS, particularly in parameters associated with cardiovascular risk. A significant association of obesity rather than raised testosterone with this dyslipidemia was also confirmed by the study.//////////////////

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created: Aug. 1, 2006, 1:38 p.m. by: Alex   email:
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last update: March 21, 2020, 11:27 a.m. by: hsueh    email:



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