Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence and absence of 1-methylnicotinamide (MNA) and nicotinic acid (NA)
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ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE49662 | GEO | 2013/08/09
SECONDARY ACCESSION(S): PRJNA214676
REPOSITORIES: GEO
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Project description:Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan of different species. Contrasting recent observations, we here find that overexpression of sir-2.1, the orthologue of mammalian SirT1, does extend C. elegans lifespan. Sirtuins are known to convert NAD+ into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, also in the absence of sir-2.1. Consistently, impairment of sir-2.1 prevents extension of lifespan by nicotinic acid (NA), a NAD+ precursor. Taken together, sirtuins extend lifespan by promoting formation of MNA to generate a phase I - mediated ROS signal, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation. 9 samples: 3 mRNA profiles of C.elegans 48h after L4 exposed to nicotinic acid; 3 mRNA profiles of C.elegans 48h after L4 exposed to 1-MNA; 3 mRNA profiles of C.elegans 48h after L4 as controls (H20)
2013-08-09 | E-GEOD-49662 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE4093: Resveratrol treatment of daf-16 mutant C. elegans GSE4094: N2 worms treated with Resveratrol GSE4095: Sir-2.1 low copy transgenic Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. Refer to individual Series
2006-03-07 | E-GEOD-4402 | biostudies-arrayexpress
Project description:Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. This SuperSeries is composed of the SubSeries listed below.
2006-03-08 | GSE4402 | GEO
Project description:Sir2 is an NAD+-dependent histone deacetylase, and is the founding member of a large, phylogentically conserved, family of such deacetylases called the Sirtuins. The budding yeast, Saccharomyces cerevisiae, harbors 4 paralogs of Sir2, known as Hst1, Hst2, Hst3, and Hst4. Reducing the intracellular NAD+ concentration is inhibitory for the Sirtuins, and raising the intracellular nicotinamide (NAM) concentration is inhibitory. Microarray gene expression analysis was used to identify novel classes of yeast genes whose expression is altered when either NAD+ concentration is reduced or NAM is elevated. A subset of genes involved in thiamine biosynthesis was identified as being upregulated when Sir2 or Hst1 was inactivated. Several mutants in the NAD+ biosynthesis and salvage pathways were tested, along with WT and WT grown in the presence of 5 mM nicotinamide, which inhibits the Sirtuins.
2010-05-11 | GSE18488 | GEO
Project description:Sir2 is an NAD+-dependent histone deacetylase, and is the founding member of a large, phylogentically conserved, family of such deacetylases called the Sirtuins. The budding yeast, Saccharomyces cerevisiae, harbors 4 paralogs of Sir2, known as Hst1, Hst2, Hst3, and Hst4. Reducing the intracellular NAD+ concentration is inhibitory for the Sirtuins, and raising the intracellular nicotinamide (NAM) concentration is inhibitory. Microarray gene expression analysis was used to identify novel classes of yeast genes whose expression is altered when either NAD+ concentration is reduced or NAM is elevated. A subset of genes involved in thiamine biosynthesis was identified as being upregulated when Sir2 or Hst1 was inactivated. Several mutants in the NAD+ biosynthesis and salvage pathways were tested, along with WT and WT grown in the presence of 5 mM nicotinamide, which inhibits the Sirtuins. Duplicate cultures in rich YPD media were grown into log phase and then harvested. The deletion mutants npt1M-bM-^HM-^F, bna1M-bM-^HM-^F, tna1M-bM-^HM-^F, and pnc1M-bM-^HM-^F were compared to a wild-type (WT) strain. Additionally, a WT strain grown in the presence of 5 mM NAM was compared to WT without NAM. Total RNA was isolated and used for microarray hybridizations onto Affymetrix Yeast 2.0 Gene arrrays.
2010-05-10 | E-GEOD-18488 | biostudies-arrayexpress
Project description:Mechanisms to control the immune response are important to pathogen evasion and host defense. Gram-negative bacteria are common pathogens that can activate host immune responses through their outer membrane component, lipopolysaccharide (LPS). Macrophages activated by LPS induce cell signals that promote hypoxic metabolism, phagocytosis, and antigen presentation. Nicotinamide (NAM) is a vitamin B3 derivative and precursor in the formation of nicotinamide adenine dinucleotide (NAD), which is a required co-factor in cellular function. In this study, treatment of human monocyte derived macrophages with NAM antagonized LPS-induced responses by altering the expression of ubiquitin genes, increasing HIF-1alpha and p65/RelA ubiquitination, decreasing p65/RelA acetylation and promoting the formation of the proteasome. NAM also elevated intracellular NAD levels and altered the genetic expression of sirtuins and poly(ADP-ribose) polymerases. These NAM responses highlight post-translational events in regulating the host response to pathogens and identify the ubiquitome as a target in pathogen evasion and host defense.
2023-05-01 | GSE188206 | GEO
Project description:Sirtuin deacetylases and forkhead box class O (FOXO) transcription factors are central regulators of cell survival, cell cycle and cellular resistance to stress in response to signals from hormones, growth factors and oxidative stress. FOXO activity is modulated by the sirtuins, which function in a NAD+-dependent manner. Sirtuin activity, on the other hand is subject to inhibition by a natural compound nicotinamide (NAM). This study aims to investigate the effects of NAM on the sirtuin pathway and cellular homeostasis. It was hypothesized that NAM inhibits the sirtuin deacetylase activity, which then shifts FOXO-dependent responses away from stress resistance and towards apoptosis. Expression analysis using Affymetrix microarray was employed to determine differential gene expression in HEK293 cells in response to NAM treatment. Data analyses were performed using multiple algorithms, computational methods and interaction analyses. Significant changes in gene expression were detected with the generation of an expansive list of genes and interaction amongst gene groups were identified from the NAM treatment at different concentration. Substantial changes in expression profiles were detected for genes involved in a number of unique cellular pathways and functions, including cell cycle arrest, cellular proliferation and differentiation, metabolism, apoptotic signaling, inflammatory regulation and various disease conditions such as cancer. In addition, this study observed that sirtuin activities exhibit complex cell- and contextdependent behavior in modulating FOXO signaling. Contrasting roles of FOXOs and sirtuins appear to have opposite effects on cellular homeostasis. In addition, the coexistence of reciprocal regulations in this cell system suggested several levels of feedback control and illustrated the complexity of an existing fine-tuned regulatory network system between these two proteins. Future work aims to characterize putative regulators and effectors of sirtuin- and FOXO-related pathways using molecular approaches such and RNA interference knockdown of individual FOXO-isoforms. Inter-connectivity of the pathways will provide invaluable insight into current understanding of cell degeneration diseases such as diabetes, cancers and neurological disorders. Keywords: Serial concentration experiment
2018-12-31 | GSE9707 | GEO
Project description:Sirtuin deacetylases and forkhead box class O (FOXO) transcription factors are central regulators of cell survival, cell cycle and cellular resistance to stress in response to signals from hormones, growth factors and oxidative stress. FOXO activity is modulated by the sirtuins, which function in a NAD+-dependent manner. Sirtuin activity, on the other hand is subject to inhibition by a natural compound nicotinamide (NAM). This study aims to investigate the effects of NAM on the sirtuin pathway and cellular homeostasis. It was hypothesized that NAM inhibits the sirtuin deacetylase activity, which then shifts FOXO-dependent responses away from stress resistance and towards apoptosis. Expression analysis using Affymetrix microarray was employed to determine differential gene expression in HEK293 cells in response to NAM treatment. Data analyses were performed using multiple algorithms, computational methods and interaction analyses. Significant changes in gene expression were detected with the generation of an expansive list of genes and interaction amongst gene groups were identified from the NAM treatment at different concentration. Substantial changes in expression profiles were detected for genes involved in a number of unique cellular pathways and functions, including cell cycle arrest, cellular proliferation and differentiation, metabolism, apoptotic signaling, inflammatory regulation and various disease conditions such as cancer. In addition, this study observed that sirtuin activities exhibit complex cell- and contextdependent behavior in modulating FOXO signaling. Contrasting roles of FOXOs and sirtuins appear to have opposite effects on cellular homeostasis. In addition, the coexistence of reciprocal regulations in this cell system suggested several levels of feedback control and illustrated the complexity of an existing fine-tuned regulatory network system between these two proteins. Future work aims to characterize putative regulators and effectors of sirtuin- and FOXO-related pathways using molecular approaches such and RNA interference knockdown of individual FOXO-isoforms. Inter-connectivity of the pathways will provide invaluable insight into current understanding of cell degeneration diseases such as diabetes, cancers and neurological disorders. Keywords: Serial concentration experiment
2018-12-31 | GSE7319 | GEO
Project description:Sir2 and the homologous proteins, Hst1, Hst2, Hst3, and Hst4 from Saccharomyces cerevisiae are NAD+-dependent histone deacetylases of the sirtuin protein family. Sir2 functions in transcriptional silencing at the silent mating-type loci, telomeres, and rDNA locus, but also promotes replicative lifespan. To gain a better understanding of the chromatin-regulatory roles carried out by Sir2 and the Hst proteins, we performed ChIP-sequencing analysis on all five sirtuins and Sum1, the DNA binding partner for Hst1. Sir2, Hst1, and Sum1 were abundantly, and functionally co-enriched at several major targets, including the telomeric repeats, where they were required for maintaining proper telomere repeat length. At tRNA target genes they were required for efficient cohesin and condensin deposition. Across the open reading frames of glycolytic and ribosomal protein genes, Sir2 and Hst1 functioned in NAD+-dependent transcriptional repression at the diauxic shift, directly linking Sir2 to glucose metabolism, which could have implications for longevity. Six factors and Input ChIP-seq samples were analyzed in Saccharomyces eerevisiae.
2013-05-10 | E-GEOD-41415 | biostudies-arrayexpress