Search results for: Debra Toiber

Items from 1 to 12 out of 12 results

article

Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos

Anat Lan, Daniel Stein, Miguel Portillo, Debra Toiber, more

Behavioral and Brain Functions > 2019 > 15 > 1 > 1-9

Background Signs of pervasive developmental disorder and social deficits were reported in toddlers and children whose mothers were exposed to organophosphate pesticides during pregnancy. Deficits in social preference were reported in adult male mice exposed to chlorpyrifos on gestational days 12–15. This study aimed (a) to test the hypothesis that adult female and male mice that were exposed prenatally...

article

Epigenetic control of early neurodegenerative events in diabetic retinopathy by the histone deacetylase SIRT6

María A. Zorrilla‐Zubilete, Ada Yeste, Francisco J. Quintana, Debra Toiber, more

Journal of Neurochemistry > 144 > 2 > 128 - 138

Diabetic retinopathy (DR) is one of the common complications associated with diabetes mellitus and the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Moreover, glucose‐induced neuron and glial cell damage may occur shortly after the onset of diabetes which makes the disease hard...

article

Neuroprotective Functions for the Histone Deacetylase SIRT6

Shai Kaluski, Miguel Portillo, Antoine Besnard, Daniel Stein, more

Cell Reports > 2017 > 18 > 13 > 3052-3062

The histone deacetylase SIRT6 promotes DNA repair, but its activity declines with age with a concomitant accumulation of DNA damage. Furthermore, SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. Here, we report that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these...

chapter

Characterization of Nuclear Sirtuins: Molecular Mechanisms and Physiological Relevance

Debra Toiber, Carlos Sebastian, Raul Mostoslavsky

Handbook of Experimental Pharmacology > Histone Deacetylases: the Biology and Clinical Implication > 189-224

Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. This group of enzymes relies on nicotinamide adenine dinucleotide (NAD⁺) as a cofactor linking their activity to the cellular metabolic status. Originally found in yeast, Sir2 was discovered as a silencing factor and has been shown to mediate the effects of calorie restriction on lifespan...

article

SIRT6 Recruits SNF2H to DNA Break Sites, Preventing Genomic Instability through Chromatin Remodeling

Debra Toiber, Fabian Erdel, Karim Bouazoune, Dafne M. Silberman, more

Molecular Cell > 2013 > 51 > 4 > 454-468

DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6...

article

The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism

Carlos Sebastián, Bernadette M.M. Zwaans, Dafne M. Silberman, Melissa Gymrek, more

Cell > 2012 > 151 > 6 > 1185-1199

Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed...

article

A SIRT1-LSD1 Corepressor Complex Regulates Notch Target Gene Expression and Development

Peter Mulligan, Fajun Yang, Luisa Di Stefano, Jun-Yuan Ji, more

Molecular Cell > 2011 > 42 > 5 > 689-699

Epigenetic regulation of gene expression by histone-modifying corepressor complexes is central to normal animal development. The NAD ⁺ -dependent deacetylase and gene repressor SIRT1 removes histone H4K16 acetylation marks and facilitates heterochromatin formation. However, the mechanistic contribution of SIRT1 to epigenetic regulation at euchromatic loci and whether it acts in concert with...

article

Engineering DYRK1A overdosage yields Down syndrome-characteristic cortical splicing aberrations

Debra Toiber, Garikoitz Azkona, Shani Ben-Ari, Nuria Torán, more

Neurobiology of Disease > 2010 > 40 > 1 > 348-359

Down syndrome (DS) associates with impaired brain functions, but the underlying mechanism(s) are yet unclear. The “gene dosage” hypothesis predicts that in DS, overexpression of a single gene can impair multiple brain functions through a signal amplification effect due to impaired regulatory mechanism(s). Here, we report findings attributing to impairments in the splicing process such a regulatory...

article

The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1α

Lei Zhong, Agustina D'Urso, Debra Toiber, Carlos Sebastian, more

Cell > 2010 > 140 > 2 > 280-293

SIRT6 is a member of a highly conserved family of NAD ⁺ -dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the...

article

Pro-apoptotic protein–protein interactions of the extended N-AChE terminus

Debra Toiber, David S. Greenberg, Hermona Soreq

Journal of Neural Transmission > 2009 > 116 > 11 > 1435-1442

The N-terminally extended “synaptic” acetylcholinesterase variant N-AChE-S operates to promote apoptosis; however, the protein partners involved in this function remain unknown. Here, we report that when microinjected to fertilized mouse oocytes, N-AChE-S caused embryonic death as early as the zygotic stage. To identify the putative protein partners involved, we first tried yeast two hybrid screening,...

article

Function of alternative splicing

Stefan Stamm, Shani Ben-Ari, Ilona Rafalska, Yesheng Tang, more

Gene > 2005 > 344 > Complete > 1-20

Alternative splicing is one of the most important mechanisms to generate a large number of mRNA and protein isoforms from the surprisingly low number of human genes. Unlike promoter activity, which primarily regulates the amount of transcripts, alternative splicing changes the structure of transcripts and their encoded proteins. Together with nonsense-mediated decay (NMD), at least 25% of all alternative...

article

Cellular Stress Reactions as Putative Cholinergic Links in Alzheimer’s Disease

Debra Toiber, Hermona Soreq

Neurochemical Research > 2005 > 30 > 6-7 > 909-919

Alzheimer’s disease involves normal cellular aging and chronic cellular stress events, leading to interrelated changes in gene expression and subsequent neurodegeneration. Premature death of cholinergic neurons and the formation of amyloid fibrils separately initiated the cholinergic and amyloid hypotheses of Alzheimer’s disease. Here, we present evidence to the fact that these two distinct phenomena...

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