A5039776486- Hormonal and reproductive studies
- Peroxisome Proliferator-Activated Receptors
- Hormonal Regulation and Hypertension
- Protein Tyrosine Phosphatases
- Sperm and Testicular Function
- Mitochondrial Function and Pathology
- BRCA gene mutations in cancer
- Adipose Tissue and Metabolism
- Sexual Differentiation and Disorders
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Estrogen and related hormone effects
- Inflammatory mediators and NSAID effects
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Redox biology and oxidative stress
- Cancer, Lipids, and Metabolism
- Metabolism and Genetic Disorders
- Ion Transport and Channel Regulation
- Genomics, phytochemicals, and oxidative stress
- Ubiquitin and proteasome pathways
- Hypothalamic control of reproductive hormones
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Neuroendocrine regulation and behavior
University of Buenos Aires
2014-2024
Consejo Nacional de Investigaciones Científicas y Técnicas
2012-2024
Indian Institute of Science Bangalore
2005
American Society for Biochemistry and Molecular Biology
2005
Ellis Hospital
2005
Massachusetts Eye and Ear Infirmary
1995
Smith-Kettlewell Eye Research Institute
1995
Harvard University
1995
University of Miami
1993
Fundación Instituto Leloir
1993
Discrepancies between adenosine 3':5'-cyclic monophosphate (cAMP) and steroid production have been frequently observed in isolated target cells stimulated by low concentrations of trophic hormone. This dissociation is particularly marked the interstitial testis, where testosterone elicited gonadotropin picomolar range. Because these observations, a disparity steroidogenesis protein kinase (ATP: phosphotransferase, EC 2.7.1.37) activation Leydig cells, role cAMP as mediator acute...
Although the contribution of mitochondrial dynamics (a balance in fusion/fission events and changes mitochondria subcellular distribution) to key biological process has been reported, fusion achieve efficient steroid production never explored. The are central during synthesis different enzymes localized between endoplasmic reticulum produce final hormone, thus suggesting that might be relevant for this process. In present study, we showed hormonal stimulation triggers into tubular-shaped...
ERK1/2 is known to be involved in hormone-stimulated steroid synthesis, but its exact roles and the underlying mechanisms remain elusive. Both phosphorylation steroidogenesis may triggered by cAMP/cAMP-dependent protein kinase (PKA)-dependent and-independent mechanisms; however, activation cAMP results a maximal steroidogenic rate, whereas canonical epidermal growth factor (EGF) does not. We demonstrate herein Western blot analysis confocal studies that temporal mitochondrial obligatory for...
Endogenous concentrations of testosterone (T), 5µ-androstan-3µ,17β-diol (DIOL) and dihydrotestosterone (DHT) were determined in whole testis, seminiferous tubules interstitial tissue rats from 10 to 90 days age. Contents testis very close the sum contents tissue. In concentration T increased 39 ng/100 mg proteins at 14 94 20 days, then dropped 13 26 days. There was a gradual increase thereafter reach again value sexual maturation. The DIOL also 21 89 20-day-old rats, but it remained high...
The acyl-CoA synthetase 4 (ACSL4) is increased in breast cancer, colon and hepatocellular carcinoma. ACSL4 mainly esterifies arachidonic acid (AA) into arachidonoyl-CoA, reducing free AA intracellular levels, which contradiction with the need for metabolites tumorigenesis. Therefore, causal role of still not established. This study was undertaken to determine metabolic pathway cancer cells. first novel finding that regulates expression cyclooxygenase-2 (COX-2) production prostaglandin...
The rate-limiting step in the biosynthesis of steroid hormones, known as transfer cholesterol from outer to inner mitochondrial membrane, is facilitated by StAR, Steroidogenic Acute Regulatory protein. We have described that ERK1/2 phosphorylates StAR and fusion, through up-regulation a fusion protein Mitofusin 2, essential during steroidogenesis. Here, we demonstrate together with active ERK PKA are necessary for maximal production. Phosphorylation required maintenance this mitochondria,...
Whole testicular tissue, isolated seminiferous tubules and interstitial tissue of developing rats were incubated with testosterone–14C. After incubation, several steroid metabolites by paper thin—layer chromatography derivative formation. They usually accounted for more than 90% the radioactivity added as Losses corrected tritiated tracers. Identification products was confirmed recrystallization. 5α–Androstandiol– 14C main metabolite from tubules, dihydrotestosterone–14C androsterone– other...
The acyl-CoA synthetase 4 (ACSL4), which esterify mainly arachidonic acid (AA) into acyl-CoA, is increased in breast, colon and hepatocellular carcinoma. transfection of MCF-7 cells with ACSL4 cDNA transforms the a highly aggressive phenotype controls both lipooxygenase-5 (LOX-5) cyclooxygenase-2 (COX-2) metabolism AA, suggesting causal role tumorigenesis. We hypothesized that ACSL4, LOX-5 COX-2 may constitute potential therapeutic targets for control tumor growth. Therefore, aim this study...
The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer patients has been scarcely investigated outside Europe and North America, with few reports for South where Amerindian founder effects recent multiracial immigration are predicted to result high diversity. We describe here the results BRCA1/BRCA2 germline analysis an Argentinean series breast/ovarian selected young age at diagnosis or family history.The study (134 patients) included 37 cases diagnosed within 40 years no...
// Ulises D. Orlando 1, * , Ana F. Castillo Melina A. Dattilo 1 Angela R. Solano Paula M. Maloberti Ernesto J. Podesta Biomedical Research Institute, INBIOMED, Department of Biochemistry, School Medicine, University Buenos Aires, CABA, Argentina These authors have contributed equally to this work Correspondence to: Podesta, e-mail: ernestopodesta@yahoo.com.ar ; biohrdc@fmed.uba.ar Keywords: arachidonic acid, cancer, cell signaling, gene expression, tamoxifen Received: May 14, 2015 Accepted:...
Acyl-CoA thioesterases, also known as acyl-CoA hydrolases, are a group of enzymes that hydrolyze CoA esters such acyl-CoAs (saturated, unsaturated, branched-chain), bile acid-CoAs, prostaglandins, etc., to the corresponding free acid and CoA. However, there is significant confusion regarding nomenclature these genes. In agreement with HUGO Gene Nomenclature Committee Mouse Genomic Committee, revised for mammalian thioesterases/hydrolases has been suggested 12 member family. The family root...
Because several groups have recently questioned a mediating role for cyclic AMP in adrenocortical steroidogenesis, we analysed the problem more detail by measuring three different pools cells isolated from decapsulated rat adrenals. Extra-cellular, total intracellular and bound were determined radioimmunoassay comparison with corticosterone production induced low corticotropin concentrations. The increase extracellular concentrations was dependent on presence of phosphodiesterase inhibitor...
Arachidonic acid and its lypoxygenated metabolites play a fundamental role in the hormonal regulation of steroidogenesis. Reduction expression mitochondrial acyl-CoA thioesterase (MTE-I) by antisense or small interfering RNA (siRNA) arachidonic acid-preferring synthetase (ACS4) siRNA produced marked reduction steroid output cAMP-stimulated Leydig cells. This effect was blunted permeable analog cholesterol that bypasses rate-limiting step steroidogenesis, transport from outer to inner...
Antibodies against the lutropin receptor have been obtained by monoclonal antibody technique. Mice were immunized with luteal membrane from ovaries pseudopregnant rats, containing high concentration. Hybridoma cells fusing mouse myeloma spleen animal. Five clones produced that secreted antibodies specifically inhibited binding to its in a competitive fashion. three capable of blocking biological response (e.g., testosterone production isolated rat Leydig cells). two other clones, however,...
The physical properties of detergent-solubilized gonadotropin receptor-hormone complexes, determined by density gradient centrifugation and gel filtration, were compared after in vivo vitro labeling specific ovarian binding sites with radioiodinated human chorionic (hCG). Following intravenous administration biologically active 125I-labeled hCG, up to 50% the tracer was bound luteinized ovaries immature female rats treated pregnant mare serum/human gonadotropin. Comparable hCG observed...
Acyl-CoA synthetase 4 (ACSL4) is implicated in fatty acid metabolism with marked preference for arachidonic (AA). ACSL4 plays crucial roles physiological functions such as steroid synthesis and pathological processes tumorigenesis. However, factors regulating mRNA and/or protein levels are not fully described. Because expression requires tyrosine phosphatase activity, this study we aimed to identify the involved expression. NSC87877, a specific inhibitor of SHP2, reduced ACSL4-rich breast...
BRCA1/2 mutations in Latin America are scarcely documented and serious need of knowledge about the spectrum BRCA pathogenic variants, information which may alter clinical practice subsequently improve patient outcome. In addition, search for data on testing policies different regions constitutes a fundamental strength present study, analyzes gene sequences large rearrangements 940 probands with familial and/or personal history breast/ovary cancer (BOC). non-mutated DNA samples, Multiplex...
Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models breast cancer. We assessed effects using human MCF-7 MDA‑MB‑231 carcinoma cells, well highly metastatic F3II cell line. Effect vitro cancer growth evaluated...
Acyl-CoA synthetase 4 (ACSL4) overexpression plays a causal role in the aggressiveness of triple negative breast cancer. In turn, correlation has been established between ACSL4 and estrogen receptor alpha (ERα) expression. However, upstream regulatory mechanisms leading to differential expression cancer ERα-positive cells remained unknown. We performed characterization human promoter identification transcription factors involved. Deletional analysis demonstrated proximal 43 base pairs are...