Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam binding inhibitor in steroidogenesis

Papadopoulos, Vassilios; Brown, Andrea

doi:10.1016/0960-0760(95)00027-w

Cited by 96 publications

(51 citation statements)

References 47 publications

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“…2). Diazepam-binding inhibitor (DBI) is a polypeptide found in several organisms that has been shown to be involved in benzodiazepine receptor modulation, acyl CoA metabolism, steroidogenesis, insulin secretion, and drug dependence (36,37). The relative transcript expression of DBI in Rst(2)DDT 91-R and Rst(2)DDT Wisconsin was 108-and 89-fold greater than Canton-S, suggesting a possible association between DDT resistance and cholesterol metabolism (Fig.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide transcription profile of field- and laboratory-selected dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila

Pedra

McIntyre

Scharf

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

212

268

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Genome-wide microarray analysis (Affymetrix array) was used (i) to determine whether only one gene, the cytochrome P450 enzyme Cyp6g1, is differentially transcribed in dichlorodiphenyltrichloroethane (DDT)-resistant vs. -susceptible Drosophila; and (ii) to profile common genes differentially transcribed across a DDT-resistant field isolate [Rst(2)DDT Wisconsin ] and a laboratory DDT-selected population [Rst(2)DDT 91-R ]. Statistical analysis (ANOVA model) identified 158 probe sets that were differentially transcribed among Rst(2)DDT 91-R , Rst(2)DDT Wisconsin , and the DDT-susceptible genotype Canton-S (P < 0.01). The cytochrome P450 Cyp6a2 and the diazepam-binding inhibitor gene (Dbi) were over transcribed in the two DDT-resistant genotypes when compared to the wild-type Drosophila, and this difference was significant at the most stringent statistical level, a Bonferroni correction. The list of potential candidates differentially transcribed also includes 63 probe sets for which molecular function ontology annotation of the probe sets did not exist. A total of four genes (Cyp6a2, Dbi, Uhg1, and CG11176) were significantly different (P < 5.6 e ؊06 ) between Rst(2)DDT 91-R and Canton-S. Additionally, two probe sets encoding Cyp12d1 and Dbi were significantly different between Rst(2)DDT Wisconsin and Canton-S after a Bonferroni correction. Fifty-two probe sets, including those associated with pesticide detoxification, ion transport, signal transduction, RNA transcription, and lipid metabolism, were commonly expressed in both resistant lines but were differentially transcribed in Canton-S. Our results suggest that more than Cyp6g1 is overtranscribed in field and laboratory DDT-resistant genotypes, and the number of commonalities suggests that similar resistance mechanisms may exist between laboratory-and field-selected DDT-resistant fly lines.T he evolution of insecticide resistance is often, but not always, based on major effect alleles (1-4). It has been hypothesized that high selection pressure in the field will favor monogenic forms of pesticide resistance, and that selection for resistance in the laboratory will favor polygenic resistance (5-7). In early genetic studies in Drosophila, dichlorodiphenyltrichloroethane (DDT) resistance was mapped to multiple locations on chromosomes II and III (8-14). Subsequently, low-level DDT resistance was mapped to 64.5 Ϯ 2 centiMorgans on the second chromosome (15), a locus (loci) known as Rst(2)DDT.Recently, Daborn et al. (16) suggested that resistance to DDT in the field is monogenic and is due to the overexpression of a single P450 gene, Cyp6g1. Le Goff et al. (17) suggested that resistance in field isolates of both Drosophila melanogaster and Drosophila simulans is associated with overtranscription of Cyp6g1, whereas prolonged laboratory selection with DDT apparently coselects additional genes such as Cyp12d1 (18) To date, no genome-wide expression profile has been evaluated to investigate the extent to which gene transcription varies between genotypes that are resis...

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Section: Resultsmentioning

confidence: 99%

Genome-wide transcription profile of field- and laboratory-selected dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila

Pedra

McIntyre

Scharf

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

212

268

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“…ACBP is reported to play a role in a number of important physiological and biochemical functions, such as regulation of glucose-induced insulin secretion from pancreatic β-cells (32,33), stimulation of steroidogenesis through peripheral-type benzodiazepine receptor (PBR) (34)(35)(36), and modulation of cell proliferation (37). ACBP/DBI, originally described as a cytosolic protein and identified as stimulating the synthesis of pregnenolone in mitochondrial fractions, enhances steroidogenesis via PBRs.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of PGC-1α enhances cell proliferation and tumorigenesis of HEK293 cells through the upregulation of Sp1 and Acyl-CoA binding protein

Shin

Yun

Park

et al. 2015

International Journal of Oncology

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Abstract. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a coactivator interacting with multiple transcription factors, regulates several metabolic processes. Although recent studies have focused on the role of PGC-1α in cancer, the underlying molecular mechanism has not been clarified. Therefore, we evaluated the role of PGC-1α in cell proliferation and tumorigenesis using human embryonic kidney (HEK)293 cells and colorectal cancer cells. We established stable HEK293 cell lines expressing PGC-1α and examined cell proliferation, anchorage-independent growth, and oncogenic potential compared to parental HEK293 cells. To identify the molecular PGC-1α targets for increased cell proliferation and tumorigenesis, the GeneFishing™ DEG (differentially expressed genes) screening system was used. Western blot analysis and immunofluorescence staining were performed for a regulated gene product to confirm the results. Forced expression of PGC-1α in HEK293 cells promoted cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC-1α showed enhanced tumor formation when subcutaneously injected into the bilateral flanks of immunodeficient mice. The results of the GeneFishing DEG screening system identified one upregulated gene (Acyl-CoA binding protein; ACBP). Real-time RT-PCR, western blot analysis, and immunofluorescence staining showed that ACBP was markedly increased in HEK293 cells stably overexpressing PGC-1α (PGC-1α-HEK293 cells) compared to those expressing an empty vector. In PGC-1α, ACBP, and specificity protein 1 (Sp1) siRNA knockdown experiments in PGC-1α-HEK293 and SNU-C4 cells, we also observed inhibition of cell proliferation, reduced expression of antioxidant enzymes, and increased H 2 O 2 -induced reactive oxygen species production and apoptosis. These findings suggest that PGC-1α may promote cell proliferation and tumorigenesis through upregulation of ACBP. We provide evidence that increased Sp1 expression might contribute to enhanced ACBP expression by PGC-1α. The current results also suggest that PGC-1α, whose expression is related to enhanced cell proliferation and tumorigenesis, may be a good candidate molecular target for cancer therapy.

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“…Subsequent studies from several laboratories have shown that these changes in 30-kDa proteins occur in adrenal, testis, and ovarian cells of several species (13)(14)(15)(16)21). The peripheral benzodiazepine receptor that is localized in the adrenal mitochondrial outer membrane is also essential for this step, suggesting the involvement of a complex multistep process (17,18).…”

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confidence: 99%

Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

Ariyoshi¹,

Kim²,

Artemenko

et al. 1998

Journal of Biological Chemistry

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The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3.5-kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating (ϳ85% of total) in vivo. Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold.

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Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam binding inhibitor in steroidogenesis

Cited by 96 publications

References 47 publications

Genome-wide transcription profile of field- and laboratory-selected dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila

Genome-wide transcription profile of field- and laboratory-selected dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila

Overexpression of PGC-1α enhances cell proliferation and tumorigenesis of HEK293 cells through the upregulation of Sp1 and Acyl-CoA binding protein

Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

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