Transcriptional regulation of the CYP11A1 and ferredoxin genes

Chung, Bon Chu; Guo, Ing-Cherng; Chou, Shen Ju

doi:10.1016/s0039-128x(96)00156-0

Cited by 48 publications

(25 citation statements)

References 45 publications

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“…Furthermore, the morphant studies reported herein demonstrate that the zebrafi sh is an excellent vertebrate model system to further Recent studies have established that NP-C pathology is enhanced by a physiological defi ciency state (21)(22)(23), as cholesterol sequestration in late endosomes and lysosomes consequently limits substrates for steroid biosynthesis ( 23 ). Cholesterol-derived steroid hormones include mineralocorticoids, glucocorticoids, sex hormones, and neurosteroids that collectively control important physiological functions, such as electrolyte balance, glucose homeostasis, and sexual development ( 24,25 ). Normal steroid hormone metabolism is disrupted in fl ies and mice where Npc1 and Npc2 have been genetically inactivated (21)(22)(23)26 ).…”

Section: This Work Was Supported By a Ruth L Kirschtein Predoctoral mentioning

confidence: 76%

“…IIG-N), as were the markers cldnE and krt8 (data not shown). Moreover, YSL nuclei marked ( 25,75 ). Knockdown of cyp11a by MO in the zebrafi sh results in an epiboly-delay defect that can be partially rescued by incubating cyp11a morphants in P5 at early developmental stages prior to the doming of the yolk ( 37 ).…”

Section: Disruption Of Npc1 Function Results In Actin Cytoskeleton DImentioning

confidence: 99%

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Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Schwend

Loucks

Snyder

et al. 2011

Journal of Lipid Research

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This article is available online at http://www.jlr.org ( 1,2 ). NP-C symptoms typically appear in childhood, although infant onsets are possible. By the time the disorder's symptoms manifest, signifi cant cellular damage has already occurred. At the cellular level, NP-C is characterized by an aberrant accumulation of unesterifi ed cholesterol and glycolipids in the late endosomes and lysosomes of the endocytotic pathway ( 3-6 ). The disease is caused by mutations in one of two genes, Niemann-Pick disease, type C1 ( NPC1 ), which accounts for 95% of cases, or NiemannPick disease, type C2 ( NPC2 ), which accounts for 4% of cases. The remaining 1% of cases involves patients with confi rmed biochemical defects without an accompanying identifi ed mutation ( 7-10 ).The function of NPC1 involves regulating the movement of LDL-derived cholesterol and plasma-derived glycolipids from the endocytotic pathway to the endoplasmic reticulum/trans-Golgi network (ER/TGN) and the mitochondrial membrane ( 11-15 ). Despite reductions in sterol exit from the endocytotic pathway, NPC1-defi cient cells display normal sterol uptake, proper sterol delivery to the endocytotic organelles, and unperturbed levels of cholesterol ester hydrolysis ( 3,16,17 ). Excessive sterol content in the liver and spleen likely accounts for reports of hepato-splenomegaly, whereas sterol accumulation in the brain may contribute to the neurological deterioration in NP-C patients ( 16,(18)(19)(20).Abstract Niemann-Pick disease, type C (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafi sh npc1 and analyzed its gene expression and activity by reducing Npc1 protein with morpholino (MO)-oligonucleotides. Filipin staining in npc1-morphant cells was punctate, suggesting abnormal accumulation of cholesterol. Developmentally, reducing Npc1 did not disrupt early cell fate or survival; however, early morphogenetic movements were delayed, and the actin cytoskeleton network was abnormal. MO-induced defects were rescued with ectopic expression of mouse NPC1 , demonstrating functional gene conservation, and by treatments with steroids pregnenolone or dexamethasone, suggesting that reduced steroidogenesis contributed to abnormal cell movements. Cell death was found in anterior tissues of npc1 morphants at later stages, consistent with fi ndings in mammals. Collectively, these studies show that npc1 is required early for proper cell movement and cholesterol localization and later for cell survival. -Schwend, T., E. J. Loucks, D. Snyder, and S. C. Ahlgren. Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafi sh. J.

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Section: This Work Was Supported By a Ruth L Kirschtein Predoctoral mentioning

confidence: 76%

Section: Disruption Of Npc1 Function Results In Actin Cytoskeleton DImentioning

confidence: 99%

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Schwend

Loucks

Snyder

et al. 2011

Journal of Lipid Research

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“…Meanwhile, steroid 17a-hydroxylase and 3b-dehydrogenase can be regulated by cyclic AMP and protein kinase C secondary messenger system (Lund et al, 1997). Among all the positive gene regulations in hormone production, CREB, a highly expressive transcription factor in adrenal cortex, regulated steroid production by binding with frequently present CREB binding site in the promoter region of genes which encoding steroidogenic enzymes (Tsukiyama et al, 1994;Chung et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway

Chen

et al. 2002

Br J Cancer

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The result of our previous study has shown that the K-ras mutant (pK568MRSV) transfected human adrenocortical cells can significantly increase cortisol production and independently cause cell transformation. The aim of this study is to investigate the effect of the active K-ras oncogene on the cortisol production in normal human adrenocortical cells. First we used isopropyl thiogalactoside to induce the inducible mutant K-ras expression plasmid, pK568MRSV, in the stable transfected human adrenocortical cells. The result showed that the increase of RasGTP levels in transfected cells was time-dependent after isopropyl thiogalactoside induction. Additionally, results from Western blot analysis revealed significant elevation in phosphorylation of c-Raf-1 and Mitogen-activated protein kinase. We also detected the levels of mRNA encoding Cholesterol side-chain cleavage enzyme (P450 SCC ), 17a-Hydroxylase/17,20-lyase (P450 c17 ) and 3b-Hydroxysteroid dehydrogenase (3bHSD) were increased in human adrenocortical cells transfected with mutant K-ras after IPTG treatment. The increase of mRNA amount in P450 scc P450 c17 and 3bHSD and the elevation of cortisol level were inhibited with a pretreatment of PD098059, a specific extracellular signal-regulated kinase inhibitor. In our previous report, we proved that lovastatin, a pharmacological inhibitor of p21 ras function, also reversed the increase of cortisol level in mutant K-ras stably transfected human adrenocortical cells. Taken together, these findings proved that the active mutant Ras enhanced not only cell proliferation but also steroidogenesis in steroidogenic phenotype cells by activating Raf-MEK-MAPK related signal transduction pathway. Therefore, we believe that K-ras mutants influence regulation of steroidogenesis in adrenocortical cells through RAF-MEK-MAPK pathway.

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“…Pregnenolone is the common precursor in the steroidogenesis pathway, which leads to the synthesis of mineralocorticoids, glucocorticoids, and sex hormones. The enzyme P450scc is encoded by a single human gene, CYP11A1 (2), on chromosome 15q23-24 (3), and its expression is regulated hormonally at the transcriptional level (4). Although expression of the gene has been detected in the central nervous system (5), P450scc transcript and protein are expressed for the most part in steroidogenic tissues such as adrenals, ovaries (6), testis, and the placenta (7)(8)(9).…”

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confidence: 99%

The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

Gizard

Lavallée

Dewitte

et al. 2002

Journal of Biological Chemistry

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Transcriptional regulation of the CYP11A1 and ferredoxin genes

Cited by 48 publications

References 45 publications

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway

The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

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