Evidence for a diazepam-binding inhibitor (DBI) benzodiazepine receptor-like mechanism in ecdysteroidogenesis by the insect prothoracic gland

Snyder, Mark J.; Antwerpen, Rik van

doi:10.1007/s004410051166

Cited by 34 publications

(18 citation statements)

References 38 publications

(56 reference statements)

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“…This indicates that ACBP is expressed in an allele dosage-dependent fashion from both alleles. The immunohistochemical detections revealed that ACBP is distributed evenly in the hepatocytes from ACBP ϩ/ϩ liver and that ACBP is present both in the cytosol and in the nucleus as has been reported for other cell types (57)(58)(59)(60). Importantly, ACBP staining is completely absent from the liver of ACBP Ϫ/Ϫ mice, thereby demonstrating the specificity of the antibody.…”

Section: Resultssupporting

confidence: 70%

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Neess¹,

Bloksgaard²,

Bek³

et al. 2011

Journal of Biological Chemistry

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The mouse acyl-CoA-binding protein (ACBP) 5 /diazepam binding inhibitor is a 10-kDa intracellular protein consisting of 86 amino acids. It is highly conserved throughout evolution and expressed in all cell types in the eukaryotes investigated (1, 2). This, together with the characteristics of the ACBP promoter (3, 4), implies a housekeeping function of the gene. However, expression levels vary markedly between tissues (5) and in response to different metabolic stimuli (6 -9), thereby indicating that ACBP might perform more specialized functions in some cell types. The ACBP protein binds C 14 -C 22 acyl-CoA esters with high affinity and specificity (10, 11) and has very little or no affinity toward other ligands (11-13). From in vitro studies, ACBP is known to protect acyl-CoA esters from hydrolysis (14 -16) and to relieve acyl-CoA inhibition of a number of enzymes, including long chain acyl-CoA synthetase, acetyl-CoA carboxylase (ACC), adenine nucleotide translocase, fatty acid synthetase (FAS), carnitine palmitoyltransferase, and acyl-CoA:cholesterol acyltransferase (9, 16 -18). In addition, ACBP is known to donate acyl-CoA esters to phospholipid, glycerolipid, and cholesteryl ester (CE) synthesis (14, 18 -21). Finally, proteolytic products of secreted ACBP have been shown to have signaling functions in Dictyostelium as well as mammalian cells (22). Targeted disruption of the yeast ACBP gene (ACB1) revealed that ACBP deficiency results in increased levels of C18:0 acyl-CoA esters and a decrease in the amount of total C26:0 fatty acids, indicating that transport of FA toward elongation is impaired by lack of ACBP. Furthermore, sphingolipid and ceramide amounts were reduced, membrane structure was altered, and vesicular transport was compromised (23-25).The functions of ACBP in lipid metabolism have been further studied in different mammalian cell culture systems and animal models by both knockdown strategies and overexpression of the protein. It has been reported that knockdown of ACBP by small interfering RNA causes growth arrest and lethality in three different mammalian cell lines (26); however, data from our laboratory show that ACBP can be knocked down in many different cell systems without affecting growth and survival (27). 6 Recently, knockdown of ACBP in HepG2 cells was shown to suppress the expression of a number of genes involved in lipid biosynthesis and lead to decreased levels of saturated and monounsaturated fatty acids (28). In 3T3-L1 preadipocytes, knockdown of ACBP caused a mild impairment of adipocyte differentiation and accumulation of triacylglycerol (TAG) (27), whereas overexpression of ACBP in McA-RH7777 rat hepatoma cells resulted in increased intracellular TAG accumulation (29). Overexpression of ACBP in transgenic mice resulted in accumulation of different lipid classes, including TAG in the liver (30). These results suggest *

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Section: Resultssupporting

confidence: 70%

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Neess¹,

Bloksgaard²,

Bek³

et al. 2011

Journal of Biological Chemistry

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“…For instance, cholesterol transport into mitochondria is the rate-determining step in steroidogenesis (8,11). TSPO serves the similar function in plants (12), insects (13), and mammals (14). However, the appearance of the drug, such as the benzodiazepine diazepam, binding sites on TSPO evolved later than the brain-specific ␥-aminobutyric acid A receptor benzodiazepine binding sites (15), although drug binding was observed in both the plant and insect TSPOs (12,13).…”

Section: Translocator Protein (Tspo)mentioning

confidence: 99%

“…TSPO serves the similar function in plants (12), insects (13), and mammals (14). However, the appearance of the drug, such as the benzodiazepine diazepam, binding sites on TSPO evolved later than the brain-specific ␥-aminobutyric acid A receptor benzodiazepine binding sites (15), although drug binding was observed in both the plant and insect TSPOs (12,13). Thus, throughout evolution, mammalian Tspo genes have exhibited extraordinary plasticity, a valuable trait to be further exploited.…”

Section: Translocator Protein (Tspo)mentioning

confidence: 99%

Translocator Protein 2 Is Involved in Cholesterol Redistribution during Erythropoiesis

Fan

Rone

Papadopoulos

2009

Journal of Biological Chemistry

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Translocator protein (TSPO) is an 18-kDa cholesterol-and drug-binding protein conserved from bacteria to humans. While surveying for Tspo-like genes, we identified its paralogous gene, Tspo2, encoding an evolutionarily conserved family of proteins that arose by gene duplications before the divergence of avians and mammals. Comparative analysis of Tspo1 and Tspo2 functions suggested that Tspo2 has become subfunctionalized, typical of duplicated genes, characterized by the loss of diagnostic drug ligandbinding but retention of cholesterol-binding properties, hematopoietic tissue-and erythroid cell-specific distribution, and subcellular endoplasmic reticulum and nuclear membrane localization. Expression of Tspo2 in erythroblasts is strongly correlated with the down-regulation of the enzymes involved in cholesterol biosynthesis. Overexpression of TSPO2 in erythroid cells resulted in the redistribution of intracellular free cholesterol, an essential step in nucleus expulsion during erythrocyte maturation. Taken together, these data identify the TSPO2 family of proteins as mediators of cholesterol redistribution-dependent erythroblast maturation during mammalian erythropoiesis.Translocator protein (TSPO) 2 is an 18-kDa protein that was previously known as PBR (peripheral type benzodiazepine receptor) and represents a gene family evolutionarily conserved from bacteria to humans (1). In bacteria, TSPO is the tryptophan-rich sensory protein, an integral membrane protein that acts as a negative regulator of the expression of specific photosynthesis genes in response to oxygen and light (2). It is involved in the efflux of porphyrin intermediates from the cell, and several conserved aromatic residues within TSPO are thought to be involved in binding porphyrin intermediates (2). TSPO of bacterial origin has been shown to have the same ligand binding properties as mammalian TSPO proteins (3). In addition to the binding of porphyrin and heme, mammalian TSPO can replace the activity of its bacterial homologs (2, 4, 5). Rat TSPO was shown to retain its structure within the bacterial outer membrane, to functionally substitute for the bacterial homolog, and to act in a manner similar to TSPO in the outer mitochondrial membrane (6). Therefore, it is conceivable that some conserved functions of the Tspo genes within a cell are maintained from bacteria to plants and to mammals.In mammals, the biological significance of TSPO has been studied for decades, and TSPO has been shown to be involved in a variety of cellular functions, including cholesterol transport and steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and proliferation (7-10). Moreover, its expression correlates with certain pathological conditions such as cancer and endocrine and neurological diseases (8). Although some conserved cellular functions of Tspo are shared from bacteria to mammals, such as cholesterolbinding and transport, their biological significance seems to have adapted to serve specific functions critica...

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“…Acyl-CoA is transported in the cytoplasm by specific acyl-CoA-binding proteins (ACBP) (Knudsen et al, 2000). ACBP has been identified in the midgut and prothoracic gland of M. sexta (Snyder and Van Antwerpen, 1997;Snyder and Van Antwerpen, 1998), as well as in different tissues of D. melanogaster, including the oocyte (Kolmer et al, 1994). Northern blot analysis has indicated that the ovaries of M. sexta also express ACBP (Snyder and Feyereisen, 1993), indicating the possible involvement of this protein in the cytosolic transport of acyl-CoAs in oocytes of M.sexta.…”

Section: Intracellular Lipid Transportmentioning

confidence: 99%

Lipid uptake by insect oocytes

Ziegler

Antwerpen

2006

Insect Biochemistry and Molecular Biology

202

172

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Evidence for a diazepam-binding inhibitor (DBI) benzodiazepine receptor-like mechanism in ecdysteroidogenesis by the insect prothoracic gland

Cited by 34 publications

References 38 publications

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Translocator Protein 2 Is Involved in Cholesterol Redistribution during Erythropoiesis

Lipid uptake by insect oocytes

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