Abstract:
:Translocator protein (TSPO) is a key member of the mitochondrial cholesterol transport complex in steroidogenic tissues. To assess the function of TSPO, we generated two lines of Cre-mediated Tspo conditional knockout (cKO) mice. First, gonadal somatic cell-targeting Amhr2-Cre mice were crossed with Tspo-floxed mice to obtain F1 Tspo Amhr2 cKO mice (Tspo(fl/fl);Amhr2-Cre(/+)). The unexpected Mendelian ratio of 4.4% cKO mice was confirmed by genotyping of 12.5-day-postcoitum (dpc) embryos. As Amhr2-Cre is expressed in gonads at 12.5 dpc, these findings suggest preimplantation selection of embryos. Analysis of expression databases revealed elevated levels of Amhr2 in two- and eight-cell zygotes, suggesting ectopic Tspo silencing before the morula stage and demonstrating elevated embryonic lethality and involvement of TSPO in embryonic development. To circumvent this issue, steroidogenic cell-targeting Nr5a1-Cre mice were crossed with Tspo-floxed mice. The resulting Tspo(fl/fl);Nr5a1-Cre(/+) mice were born at a normal Mendelian ratio. Nr5a1-driven Tspo cKO mice exhibited highly reduced Tspo levels in adrenal cortex and gonads. Treatment of mice with human chorionic gonadotropin (hCG) resulted in increased circulating testosterone levels despite extensive lipid droplet depletion. In contrast, Nr5a1-driven Tspo cKO mice lost their ability to form corticosterone in response to adrenocorticotropic hormone (ACTH). Important for ACTH-dependent steroidogenesis, Mc2r, Stard1, and Cypa11a1 levels were unaffected, whereas Scarb1 levels were increased and accumulation of lipid droplets was observed, indicative of a blockade of cholesterol utilization for steroidogenesis. TSPO expression in the adrenal medulla and increased epinephrine production were also observed. In conclusion, TSPO was found necessary for preimplantation embryo development and ACTH-stimulated steroid biosynthesis.
journal_name
Proc Natl Acad Sci U S Aauthors
Fan J,Campioli E,Midzak A,Culty M,Papadopoulos Vdoi
10.1073/pnas.1502670112subject
Has Abstractpub_date
2015-06-09 00:00:00pages
7261-6issue
23eissn
0027-8424issn
1091-6490pii
1502670112journal_volume
112pub_type
杂志文章abstract::Brief incubation of partially purified preparations of hormone-sensitive lipase from rat epididymal fat pads with ATP, Mg(++), cyclic adenosine 3':5'-monophosphate and rabbit muscle protein kinase (phosphorylase b kinase kinase) resulted in enhancement of lipolytic activity (44-93%). Little or no activation was observ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.67.1.290
更新日期:1970-09-01 00:00:00
abstract::Migrations allow animals to track seasonal changes in resources, find mates, and avoid harsh climates, but these regular, long-distance movements also have implications for parasite dynamics and animal health. Migratory animals have been dubbed "superspreaders" of infection, but migration can also reduce parasite burd...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1908777117
更新日期:2020-05-19 00:00:00
abstract::Chemoresistance of cisplatin therapy is related to extensive repair of cisplatin-modified DNA in the nucleus by the nucleotide excision repair (NER). Delivering cisplatin to the mitochondria to attack mitochondrial genome lacking NER machinery can lead to a rationally designed therapy for metastatic, chemoresistant ca...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1405244111
更新日期:2014-07-22 00:00:00
abstract::Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1406103111
更新日期:2014-06-10 00:00:00
abstract::The medial preoptic area has been shown to be intricately involved in many behaviors, including locomotion, sexual behavior, maternal care, and aggression. The gene encoding estrogen receptor-α (ERα) protein is expressed in preoptic area neurons, and a very dense immunoreactive field of ERα is found in the preoptic re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1214094109
更新日期:2012-10-02 00:00:00
abstract::Clinical studies have revealed that genetic variations in metabotropic glutamate receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the prefrontal cortex (PFC) and may be linked to psychiatric conditions such as schizophrenia, bipolar disorder, and addiction. We have performed a series of studies ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1416196112
更新日期:2015-01-27 00:00:00
abstract::Regulatory mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to induce local damage, independent of genetic manipula...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1523681113
更新日期:2016-02-16 00:00:00
abstract::The caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans. Many members of the Bcl-2 family, including Bcl-XL, are potent inhibitors of programmed cell death and inhibit activation of caspases in cells. Here, we report a direct...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.2.554
更新日期:1998-01-20 00:00:00
abstract::It has been proposed that horizontal cells of the vertebrate retina have a negative feedback synapse with cone photoreceptors. gamma-Aminobutyric acid (GABA) has been suggested to be a neurotransmitter of monophasic horizontal cells (a subtype of horizontal cells), which have direct connections with red-sensitive and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.24.7961
更新日期:1984-12-01 00:00:00
abstract::We predict by first principles a phase transition in alumina at approximately 3.7 Mbar and room temperature from the CaIrO(3)-type polymorph to another with the U(2)S(3)-type structure. Because alumina is used as window material in shock-wave experiments, this transformation should be important for the analysis of sho...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0711925105
更新日期:2008-05-06 00:00:00
abstract::Organic substances can adopt an amorphous solid or semisolid state, influencing the rate of heterogeneous reactions and multiphase processes in atmospheric aerosols. Here we demonstrate how molecular diffusion in the condensed phase affects the gas uptake and chemical transformation of semisolid organic particles. Flo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1103045108
更新日期:2011-07-05 00:00:00
abstract::The antitumor drug Taxol stabilizes microtubules and reduces their dynamicity, promoting mitotic arrest and cell death. Upon assembly of the alpha/beta-tubulin heterodimer, GTP bound to beta-tubulin is hydrolyzed to GDP reaching a steady-state equilibrium between free tubulin dimers and microtubules. The binding of Ta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0603704103
更新日期:2006-07-05 00:00:00
abstract::Aptamers recognize their targets with extraordinary affinity and specificity. The aptamer-based therapeutic, Macugen, is derived from a modified 2'fluoro pyrimidine RNA inhibitor to vascular endothelial growth factor (VEGF) and is now being used to treat the wet form of age-related macular degeneration. This VEGF(165)...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0509069102
更新日期:2005-12-27 00:00:00
abstract::Insect molting and metamorphosis are induced by steroid hormones named ecdysteroids, whose production is regulated by various neuropeptides. We cloned the gene and analyzed the expression of the prothoracicostatic peptide, a unique neuropeptide shown to suppress the production of ecdysteroids in the prothoracic gland ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0907471107
更新日期:2010-02-02 00:00:00
abstract::Recent work using culture-independent methods suggests that the lungs of cystic fibrosis (CF) patients harbor a vast array of bacteria not conventionally implicated in CF lung disease. However, sampling lung secretions in living subjects requires that expectorated specimens or collection devices pass through the oroph...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1107435109
更新日期:2012-08-21 00:00:00
abstract::The Fas/APO-1 cytotoxic pathway plays an important role in the regulation of peripheral immunity. Recent evidence indicates that this regulatory function operates through deletion of activated T and B lymphocytes by CD4+ T cells expressing the Fas ligand. Because macrophages play a key role in peripheral immunity, we ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.24.11225
更新日期:1995-11-21 00:00:00
abstract::The autoimmune dermatologic disease pemphigus vulgaris (PV) is associated with the HLA serotypes DR4 and DRw6. Susceptibility to PV could be conferred either by sequences shared between the DR4 and DRw6 haplotypes or by different sequences in these haplotypes. We have examined the distribution of DR and DQ beta-chain ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.10.3504
更新日期:1988-05-01 00:00:00
abstract::Infection of cultured cells with lytic animal viruses often results in the selective inhibition of host protein synthesis, whereas viral mRNA is efficiently translated under these circumstances. This phenomenon, known as "shut off," has been well described at the molecular level for some viruses, but there is not yet ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1004110107
更新日期:2010-05-25 00:00:00
abstract::Ceramide, a lipid mediator, has been most closely associated with antiproliferative activities. In this study, we examine the mechanism by which ceramide induces growth suppression and the role of the retinoblastoma gene product (Rb) in this process. Withdrawal of serum from the serum-dependent MOLT-4 cells resulted i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.5.1347
更新日期:1995-02-28 00:00:00
abstract::Human and murine MHC nonclassical class Ib-restricted invariant T (iT) cell subsets, such as invariant natural killer T cells (iNKT) and mucosal-associated invariant T cells, have specialized functions early in immune responses, especially in modulating subsequent adaptive immune responses. Here, we characterize a pro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1309840110
更新日期:2013-08-27 00:00:00
abstract::Conjugative DNA transfer of the self-transmissible broad-host-range plasmid RP4 is initiated by strand- and site-specific cleavage at the nick site (nic) of the transfer origin (oriT). Cleavage results in covalent attachment of the plasmid-encoded relaxase (TraI) to the 5'-terminal 2'-deoxycytidine residue at nic. We ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.7.2925
更新日期:1993-04-01 00:00:00
abstract::The binding of interferons to distinct cell surface receptors leads to the induction of synthesis of several unique polypeptides and their corresponding mRNAs (1-6). We have isolated two cDNAs that are complementary to nuclear RNA whose synthesis is induced from undetectable levels to maximal rates of transcription wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.21.6733
更新日期:1984-11-01 00:00:00
abstract::Earlier papers demonstrated an extensive genetic exchange among fluorescent Pseudomonads; this one documents for genes specifying enzymes of peripheral dissimilation an extrachromosomal array, segregation, and frequent interstrain transfer. An hypothesis is presented of a general mechanism for the formation and mainte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.3.885
更新日期:1973-03-01 00:00:00
abstract::The time-dependent Schrödinger equation is a cornerstone of quantum physics and governs all phenomena of the microscopic world. However, despite its importance, its origin is still not widely appreciated and properly understood. We obtain the Schrödinger equation from a mathematical identity by a slight generalization...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1302475110
更新日期:2013-04-02 00:00:00
abstract::T cell recognition typically involves both the engagement of a specific T cell receptor with a peptide/major histocompatibility complex (MHC) and a number of accessory interactions. One of the most important interactions is between the integrin lymphocyte function-associated antigen 1 (LFA-1) on the T cell and intrace...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.11.6302
更新日期:1998-05-26 00:00:00
abstract::We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1118833109
更新日期:2012-01-31 00:00:00
abstract::The multidimensional free energy surface for a small fast folding helical protein is explored based on first-principle calculations. The model represents the 46-residue segment from fragment B of staphylococcal protein A. The relationship between collapse and tertiary structure formation, and the order of collapse and...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.19.10161
更新日期:1997-09-16 00:00:00
abstract::Mature immunologically competent dendritic cells are the most efficient antigen-presenting cells that powerfully activate T cells and initiate and sustain immune responses. Indeed, dendritic cells are able to efficiently capture antigens, express high levels of costimulatory molecules, and produce the combination of c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.190204697
更新日期:2000-09-26 00:00:00
abstract::Multiple resistance and pH adaptation (Mrp) complexes are sophisticated cation/proton exchangers found in a vast variety of alkaliphilic and/or halophilic microorganisms, and are critical for their survival in highly challenging environments. This family of antiporters is likely to represent the ancestor of cation pum...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2006276117
更新日期:2020-12-08 00:00:00
abstract::We present a unique proxy for the reconstruction of variation in precipitation over the Amazon: oxygen isotope ratios in annual rings in tropical cedar (Cedrela odorata). A century-long record from northern Bolivia shows that tree rings preserve the signal of oxygen isotopes in precipitation during the wet season, wit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1205977109
更新日期:2012-10-16 00:00:00