Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 4 of 4

Publication Record

Connections

Molecular consequences of altered neuronal cholesterol biosynthesis.
Korade Z, Kenworthy AK, Mirnics K
(2009) J Neurosci Res 87: 866-75
MeSH Terms: Animals, Blotting, Northern, Cell Line, Cholesterol, Down-Regulation, Farnesyl-Diphosphate Farnesyltransferase, Fatty Acid Synthases, Fatty Acids, Gene Expression, Gene Expression Profiling, Intracellular Signaling Peptides and Proteins, Mice, Neurons, Oxidoreductases Acting on CH-CH Group Donors, Polymerase Chain Reaction, Proprotein Convertases, RNA, Small Interfering, Serine Endopeptidases, Sterol Regulatory Element Binding Protein 2, Sterols, Transfection, Vesicular Transport Proteins
Show Abstract · Added December 10, 2013
The first dedicated step in de novo cholesterol biosynthesis begins with formation of squalene and ends with the reduction of 7-dehydrocholesterol by 7-dehydrocholesterol reductase (Dhcr7) into cholesterol, which is an essential structural and signaling molecule. Mutations in the Dhcr7 gene lead to Smith-Lemli-Opitz syndrome (SLOS), which is characterized by developmental deformities, incomplete myelination, and mental retardation. To understand better the molecular consequences of Dhcr7 deficiency in neuronal tissue, we analyzed the effect of cholesterol deficiency on the transcriptome in Neuro2a cells. Transient down-regulation of Dhcr7 by siRNA led to altered expression of multiple molecules that play critical roles in intracellular signaling or vesicular transport or are inserted into membrane rafts (e.g. Egr1, Snx, and Adam19). A similar down-regulation was also observed in stable Dhrc7-shRNA-transfected cell lines, and the findings were verified by qPCR. Furthermore, we investigated the Dhcr7-deficient and control cells for the expression of several critical genes involved in lipid biosynthesis. Among these, fatty acid synthase, sterol-regulatory element binding protein 2, SREBF chaperone, site-1 protease, and squalene synthase showed a significant down-regulation, suggesting that, in a neuronal cell line, Dhcr7 is a potent regulator of lipid biosynthesis. Importantly, the gene expression changes were present in both lipid-containing and cholesterol-deficient media, suggesting that intrinsic cholesterol biosynthesis is necessary for normal neuronal function and cannot be supplemented from extrinsic sources.
0 Communities
2 Members
0 Resources
22 MeSH Terms
Lanosterol 14alpha-demethylase (CYP51), NADPH-cytochrome P450 reductase and squalene synthase in spermatogenesis: late spermatids of the rat express proteins needed to synthesize follicular fluid meiosis activating sterol.
Majdic G, Parvinen M, Bellamine A, Harwood HJ, Ku WW, Waterman MR, Rozman D
(2000) J Endocrinol 166: 463-74
MeSH Terms: Animals, Cholestenes, Cytochrome P-450 Enzyme System, Farnesyl-Diphosphate Farnesyltransferase, Immunoblotting, Immunohistochemistry, Leydig Cells, Liver, Male, NADPH-Ferrihemoprotein Reductase, Oxidoreductases, Rats, Rats, Sprague-Dawley, Rats, Wistar, Spermatids, Spermatogenesis, Sterol 14-Demethylase
Show Abstract · Added February 12, 2015
Lanosterol 14alpha-demethylase (CYP51) is a cytochrome P450 enzyme involved primarily in cholesterol biosynthesis. CYP51 in the presence of NADPH-cytochrome P450 reductase converts lanosterol to follicular fluid meiosis activating sterol (FF-MAS), an intermediate of cholesterol biosynthesis which accumulates in gonads and has an additional function as oocyte meiosis-activating substance. This work shows for the first time that cholesterogenic enzymes are highly expressed only in distinct stages of spermatogenesis. CYP51, NADPH-P450 reductase (the electron transferring enzyme needed for CYP51 activity) and squalene synthase (an enzyme preceding CYP51 in the pathway) proteins have been studied. CYP51 was detected in step 3-19 spermatids, with large amounts in the cytoplasm/residual bodies of step 19 spermatids, where P450 reductase was also observed. Squalene synthase was immunodetected in step 2-15 spermatids of the rat, indicating that squalene synthase and CYP51 proteins are not equally expressed in same stages of spermatogenesis. Discordant expression of cholesterogenic genes may be a more general mechanism leading to transient accumulation of pathway intermediates in spermatogenesis. This study provides the first evidence that step 19 spermatids and residual bodies of the rat testis have the capacity to produce MAS sterols in situ.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Cyclic adenosine 3',5'-monophosphate(cAMP)/cAMP-responsive element modulator (CREM)-dependent regulation of cholesterogenic lanosterol 14alpha-demethylase (CYP51) in spermatids.
Rozman D, Fink M, Fimia GM, Sassone-Corsi P, Waterman MR
(1999) Mol Endocrinol 13: 1951-62
MeSH Terms: Animals, Base Sequence, CCAAT-Enhancer-Binding Proteins, Cyclic AMP, Cyclic AMP Response Element Modulator, Cytochrome P-450 Enzyme System, DNA-Binding Proteins, Farnesyl-Diphosphate Farnesyltransferase, Gene Expression Profiling, Humans, Male, Mice, Molecular Sequence Data, Nuclear Proteins, Oxidoreductases, Promoter Regions, Genetic, Rats, Rats, Sprague-Dawley, Repressor Proteins, Response Elements, Spermatids, Sterol 14-Demethylase, Sterol Regulatory Element Binding Protein 1, Sterols, Testis, Transcription Factors
Show Abstract · Added February 12, 2015
Lanosterol 14alpha-demethylase (CYP51) produces MAS sterols, intermediates in cholesterol biosynthesis that can reinitiate meiosis in mouse oocytes. As a cholesterogenic gene, CYP51 is regulated by a sterol/sterol-regulatory element binding protein (SREBP)-dependent pathway in liver and other somatic tissue. In testis, however, cAMP/cAMP-responsive element modulator CREMtau-dependent regulation of CYP51 predominates, leading to increased levels of shortened CYP51 mRNA transcripts. CREM-/- mice lack the abundant germ cell-specific CYP51 mRNAs in testis while expression of somatic CYP51 transcripts is unaffected. The mRNA levels of squalene synthase (an enzyme preceding CYP51 in cholesterol biosynthesis in testis of CREM-/- mice are unchanged as compared with wild-type animals, showing that regulation by CREMtau is not characteristic for all cholesterogenic genes expressed during spermatogenesis. The -334/+314 bp CYP51 region can mediate both the sterol/SREBP-dependent as well as the cAMP/CREMtau-dependent transcriptional activation. SREBP-1a from somatic cell nuclear extracts binds to a conserved CYP51-SRE1 element in the CYP51 proximal promoter. The cAMP-dependent transcriptional activator CREMtau from germ cell nuclear extracts binds to a conserved CYP51-CRE2 element while no SREBP-1 binding is observed in germ cells. The two regulatory pathways mediating expression of CYP51 describe this gene as a cholesterogenic gene (SREBP-dependent expression in liver and other somatic cells) and also as a haploid expressed gene (CREMtau-dependent expression in haploid male germ cells). While in somatic cells all genes involved in cholesterol biosynthesis are regulated coordinately by the sterol/SREBP-signaling pathway, male germ cells contain alternate routes to control expression of cholesterogenic genes.
0 Communities
1 Members
0 Resources
26 MeSH Terms
Elevated expression of lanosterol 14alpha-demethylase (CYP51) and the synthesis of oocyte meiosis-activating sterols in postmeiotic germ cells of male rats.
Strömstedt M, Waterman MR, Haugen TB, Taskén K, Parvinen M, Rozman D
(1998) Endocrinology 139: 2314-21
MeSH Terms: Animals, Cytochrome P-450 Enzyme System, Farnesyl-Diphosphate Farnesyltransferase, Gene Expression, Humans, L-Lactate Dehydrogenase, Male, Meiosis, Oocytes, Oxidoreductases, RNA, Messenger, Rats, Spermatozoa, Sterol 14-Demethylase, Sterols, Testis, Tissue Distribution
Show Abstract · Added February 12, 2015
Mammalian CYP51 encodes lanosterol 14alpha-demethylase (P45014DM) that is involved in the postsqualene part of cholesterol biosynthesis. This enzyme removes the 14alpha-methyl group from lanosterol and 24,25-dihydrolanosterol producing intermediates in cholesterol biosynthesis, the oocyte meiosis-activating sterols FF-MAS and MAS-412. Human and rat CYP51 messenger RNAs (mRNAs) are expressed in all tissues, with highest levels in the testis due to the presence of an additional shorter CYP51 transcript in this tissue. In situ hybridization shows the highest CYP51 mRNA levels in seminiferous tubules, with only background levels in Leydig cells. The rat testis-specific CYP51 mRNA arises from the use of an upstream polyadenylation site and is restricted to germ cells, being most abundant in elongating spermatids in stages VII-XIV, whereas somatic CYP51 transcripts are present in all cells. In contrast, the mRNA levels of squalene synthase are maximal in round spermatids, and no germ cell-specific transcript is observed. The rat male germ cell-specific CYP51 transcript is translated in vitro to two proteins of approximately 55 and 53.5 kDa. CYP51 activity is higher in protein extracts of testes and germ cells of sexually mature rats than in prepubertal animals, in which postmeiotic germ cells are not yet present. This shows increased capacity for the production of MAS sterols by male germ cells that have already completed meiosis, suggesting that they serve a role different from meiosis activation.
0 Communities
1 Members
0 Resources
17 MeSH Terms