A5067676527- Sirtuins and Resveratrol in Medicine
- Calcium signaling and nucleotide metabolism
- Adipose Tissue and Metabolism
- Adenosine and Purinergic Signaling
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- PARP inhibition in cancer therapy
- Biochemical and Molecular Research
- Adipokines, Inflammation, and Metabolic Diseases
- Telomeres, Telomerase, and Senescence
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Chemical Reactions and Isotopes
- Tryptophan and brain disorders
- Genetic and Kidney Cyst Diseases
- Metabolism, Diabetes, and Cancer
- Lipid metabolism and disorders
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Atherosclerosis and Cardiovascular Diseases
- Hedgehog Signaling Pathway Studies
- Kruppel-like factors research
- Growth Hormone and Insulin-like Growth Factors
- Bipolar Disorder and Treatment
- Diet and metabolism studies
Institut Pasteur de Montevideo
2015-2025
Universidad de la República de Uruguay
2005-2023
Mayo Clinic
2009-2016
WinnMed
2010-2016
Mayo Clinic in Florida
2014
Mayo Clinic in Arizona
2014
Aarhus University Hospital
2014
Instituto de Investigaciones Biológicas Clemente Estable
2005-2011
Hôpital Fernand-Widal
1990
Hôpital Saint-Louis
1980
Metabolic syndrome is a growing health problem worldwide. It therefore imperative to develop new strategies treat this pathology. In the past years, manipulation of NAD(+) metabolism has emerged as plausible strategy ameliorate metabolic syndrome. particular, an increase in cellular levels beneficial effects, likely because activation sirtuins. Previously, we reported that CD38 primary NAD(+)ase mammals. Moreover, knockout mice have higher and are protected against obesity Here, show...
The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As in vitro was recently found to be negatively regulated by interaction with deleted breast cancer–1 (DBC1) protein, we set out investigate whether DBC1 regulates vivo. We and colocalized interacted, modulated activity, multiple cell lines tissues. In mouse liver, increased concomitant decreased DBC1-SIRT1...
Abstract Purpose: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth. Experimental Design: We used human cancer cells, both vitro (cell culture experiments) vivo (xenograft experiments), to demonstrate the role of cell metabolism Results: demonstrated that pharmacologic genetic targeting Nampt, key enzyme salvage pathway, inhibits growth survival cells. These changes were accompanied by reduction levels, glycolytic flux, lactate...
Aging | doi:10.18632/aging.100681. Michael B. Stout, Tamara Tchkonia, Tamar Pirtskhalava, Allyson K. Palmer, Edward O. List, Darlene E. Berryman, Ellen R. Lubbers, Carlos Escande, Adam Spong, Michal M. Masternak, Ann L. Oberg, Nathan LeBrasseur, Richard A. Miller, John J. Kopchick, Andrzej Bartke, James Kirkland
The NAD(+)-dependent deacetylase SIRT1 is a key regulator of several aspects metabolism and aging. activation beneficial for human diseases, including metabolic syndrome, diabetes, obesity, liver steatosis, Alzheimer disease. We have recently shown that the protein deleted in breast cancer 1 (DBC1) activity vivo. Furthermore, DBC1 form dynamic complex regulated by energetic state organism. Understanding how interaction between therefore essential to design strategies aimed activate SIRT1....
Macrophages exert potent effector functions against invading microorganisms but constitute, paradoxically, a preferential niche for many bacterial strains to replicate. Using model of infection by Salmonella Typhimurium, we have identified molecular mechanism regulated the nuclear receptor LXR that limits host macrophages through transcriptional activation multifunctional enzyme CD38. agonists reduced intracellular levels NAD+ in CD38-dependent manner, counteracting pathogen-induced changes...
HDAC3 is a member of the class I histone deacetylase family that regulates gene expression by deacetylation histones and non-histone proteins. activity has been shown to be modulated interaction with co-repressors NCoR SMRT. Here, we present evidence nuclear protein DBC1 an endogenous inhibitor HDAC3. previously identified as regulator some receptors, methyltransferase SUV39H1, NAD-dependent SIRT1. Furthermore, influence transcription regulation apoptosis, it may also act tumor suppressor....
Abstract Purpose: Recent studies suggest that SIRT1-activating compounds (STAC) are a promising class of anticancer drugs, although their mechanism action remains elusive. The main goal this study is to determine the role STACs as potential therapy for pancreatic cancer. In addition, we also explored by which these affect Experimental design: Using in vitro (cell culture experiments) and vivo (xenograft approaches, studied SIRT1 agonists human cancer cell viability growth. Results: We show...
Some people remain lean despite pressure to gain weight. Lean tend have high daily activity levels, but the source of this increased is unknown. We found that leanness cannot be accounted for by weight-corrected food intake in two different types rats. As previously reported people, we rats had higher levels; also expended more energy. These were developed through artificial selection aerobic endurance capacity. To test whether our findings extended a human population, measured capacity...
The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates rhythm metabolism. controls oscillations several genes protein degradation is important for maintenance also adipocyte differentiation. Elucidating mechanisms that regulate stability essential our understanding these processes. In present paper, we report DBC1 (Deleted in Breast Cancer 1) novel Rev-erbα. interact cells vivo, modulates repressor function. Depletion by siRNA (small...
The function of Krüppel-like factor 11 (KLF11) in the regulation metabolic pathways is conserved from flies to human. Alterations KLF11 result maturity onset diabetes young 7 (MODY7) and neonatal diabetes; however, mechanisms underlying role this protein disorders remain unclear. Here, we investigated how A347S genetic variant, present MODY7 patients, modulates transcriptional activity. affects a previously identified regulatory domain 3 (TRD3) for which co-regulators unknown....
Abstract Immediately after wounding, bovine corneal endothelial cells develop a fast calcium wave that propagates from the wound border to rest of monolayer and extinguishes in approximately 5 minutes. One hour late, slow ( SCW ) develops concomitantly depolarization plasma membrane potential cells. The incorporation inhibitors epithelial sodium channel sodium‐calcium exchanger produces inhibition , diminishes rate healing. L‐type blocker nimodipine does not have any effect on . reversible...
Chronic obesity leads to inflammation, tissue dysfunction, and cellular senescence. It was proposed that senescence during aging drives inflammation dysfunction. Consistent with this, clearance of senescent cells increases healthspan in progeroid mice. Here, we show the protein Deleted Breast Cancer-1 (DBC1) regulates obesity. Deletion DBC1 protects preadipocytes against senescence-driven inflammation. Furthermore, protection KO mice Finally, found participates onset response cell damage by...
Abstract Cellular senescence is an endpoint of chemotherapy, and targeted therapies in melanoma the senescence-associated secretory phenotype (SASP) can affect tumor growth microenvironment, influencing treatment outcomes. Metabolic interventions modulate SASP, enhanced mitochondrial energy metabolism supports resistance to therapy cells. Herein, we assessed function therapy-induced senescent cells obtained after exposing temozolomide (TMZ), a methylating chemotherapeutic agent. Senescence...
Cellular senescence is characterized by proliferation arrest and a senescence-associated secretory phenotype (SASP), that plays role in aging the progression of various age-related diseases. Although metabolic alterations have been reported, no consensus exists regarding mitochondrial bioenergetics. Here we compared metabolism human fibroblasts after inducing with different stimuli: oxidant hydrogen peroxide (H2O2), genotoxic doxorubicin, serial passage, or expression H-RASG12V oncogene...
The protein Deleted in Breast Cancer 1 (Dbc1) is an important regulator of various transcription factors and epigenetic modulators, significantly influencing metabolism, obesity, aging-related processes. Knockout mice lacking Dbc1 exhibit severe obesity but remain protected from liver steatosis, insulin resistance, atherosclerosis. We hypothesized that this phenotype “healthy obesity” results adipose tissue expansion, which prevents free fatty acid spillover subsequent metabolic damage to...