LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 49

Search options

  1. Article: Epigenetics of diabetic complications.

    Villeneuve, Louisa M / Natarajan, Rama

    Expert review of endocrinology & metabolism

    2013  Volume 5, Issue 1, Page(s) 137–148

    Abstract: Type 1 and Type 2 diabetes are complex diseases associated with multiple complications, and both genetic and environmental factors have been implicated in these pathologies. While numerous studies have provided a wealth of knowledge regarding the ... ...

    Abstract Type 1 and Type 2 diabetes are complex diseases associated with multiple complications, and both genetic and environmental factors have been implicated in these pathologies. While numerous studies have provided a wealth of knowledge regarding the genetics of diabetes, the mechanistic pathways leading to diabetes and its complications remain only partly understood. Studying the role of epigenetics in diabetic complications can provide valuable new insights to clarify the interplay between genes and the environment. DNA methylation and histone modifications in nuclear chromatin can generate epigenetic information as another layer of gene transcriptional regulation sensitive to environmental signals. Recent evidence shows that key biochemical pathways and epigenetic chromatin histone methylation patterns are altered in target cells under diabetic conditions and might also be involved in the metabolic memory phenomenon noted in clinical trials and animal studies. New therapeutic targets and treatment options could be uncovered from an in-depth study of the epigenetic mechanisms that might perpetuate diabetic complications despite glycemic control.
    Language English
    Publishing date 2013-09-30
    Publishing country England
    Document type Journal Article
    ISSN 1744-6651
    ISSN 1744-6651
    DOI 10.1586/eem.09.54
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Epigenetic mechanisms.

    Villeneuve, Louisa M / Natarajan, Rama

    Contributions to nephrology

    2011  Volume 170, Page(s) 57–65

    Abstract: The incidence of diabetes and related complications like nephropathy is growing rapidly and has become a major health care issue. Changes in the environment and nutritional habits have been implicated as major players. Furthermore, it is becoming ... ...

    Abstract The incidence of diabetes and related complications like nephropathy is growing rapidly and has become a major health care issue. Changes in the environment and nutritional habits have been implicated as major players. Furthermore, it is becoming increasingly clear that epigenetic factors may modulate the connections between genes and the environment. While diabetes in itself is treatable to a large extent, it is still associated with significantly increased risk for complications including chronic kidney and cardiovascular diseases. Current treatments have added preventative approaches so as to avoid future diabetic complications. Unfortunately, diabetic patients are often plagued with the continued development of various complications even after achieving glucose control. This has been suggested to be attributable to a mysterious phenomenon termed 'metabolic memory' of the prior glycemic state. Recent studies have suggested that epigenetic changes to chromatin can affect gene expression in response to various stimuli, and changes in key biochemical pathways and epigenetic histone and DNA methylation patterns in chromatin have been observed in a diabetic milieu. These accumulating data suggest that metabolic or hyperglycemic memory may be due to epigenetic changes in specific target tissues altering gene expression without changing the genetic code itself. While the genetics of diabetes has long been the focus of scientific research, much less is known about the role of epigenetics and the related molecular pathways that might affect the development of diabetes and the associated complications. Further studies of epigenetic mechanisms are therefore timely and could provide valuable new insights into the pathology of diabetic complications and also uncover much needed new therapeutic targets.
    MeSH term(s) Animals ; Clinical Trials as Topic ; Diabetes Complications/etiology ; Diabetes Complications/genetics ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans
    Language English
    Publishing date 2011-06-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1662-2782 ; 0302-5144
    ISSN (online) 1662-2782
    ISSN 0302-5144
    DOI 10.1159/000324944
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: The role of epigenetics in the pathology of diabetic complications.

    Villeneuve, Louisa M / Natarajan, Rama

    American journal of physiology. Renal physiology

    2010  Volume 299, Issue 1, Page(s) F14–25

    Abstract: Diabetes is associated with significantly accelerated rates of several debilitating microvascular complications such as nephropathy, retinopathy, and neuropathy, and macrovascular complications such as atherosclerosis and stroke. While several studies ... ...

    Abstract Diabetes is associated with significantly accelerated rates of several debilitating microvascular complications such as nephropathy, retinopathy, and neuropathy, and macrovascular complications such as atherosclerosis and stroke. While several studies have been devoted to the evaluation of genetic factors related to type 1 and type 2 diabetes and associated complications, much less is known about epigenetic changes that occur without alterations in the DNA sequence. Environmental factors and nutrition have been implicated in diabetes and can also affect epigenetic states. Exciting research has shown that epigenetic changes in chromatin can affect gene transcription in response to environmental stimuli, and changes in key chromatin histone methylation patterns have been noted under diabetic conditions. Reports also suggest that epigenetics may be involved in the phenomenon of metabolic memory observed in clinic trials and animal studies. Further exploration into epigenetic mechanisms can yield new insights into the pathogenesis of diabetes and its complications and uncover potential therapeutic targets and treatment options to prevent the continued development of diabetic complications even after glucose control has been achieved.
    MeSH term(s) Animals ; Blood Glucose/metabolism ; Chromatin Assembly and Disassembly ; DNA Methylation ; Diabetes Complications/blood ; Diabetes Complications/genetics ; Diabetic Angiopathies/blood ; Diabetic Angiopathies/genetics ; Diabetic Nephropathies/blood ; Diabetic Nephropathies/genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Humans ; MicroRNAs/metabolism ; Risk Factors ; Transcriptional Activation
    Chemical Substances Blood Glucose ; MicroRNAs
    Language English
    Publishing date 2010-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00200.2010
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Epigenetics: deciphering its role in diabetes and its chronic complications.

    Villeneuve, Louisa M / Reddy, Marpadga A / Natarajan, Rama

    Clinical and experimental pharmacology & physiology

    2011  Volume 38, Issue 7, Page(s) 451–459

    Abstract: 1. Increasing evidence suggests that epigenetic factors might regulate the complex interplay between genes and the environment, and affect human diseases, such as diabetes and its complications. 2. Clinical trials have underscored the long lasting ... ...

    Abstract 1. Increasing evidence suggests that epigenetic factors might regulate the complex interplay between genes and the environment, and affect human diseases, such as diabetes and its complications. 2. Clinical trials have underscored the long lasting beneficial effects of strict glycaemic control for reducing the progression of diabetic complications. They have also shown that diabetic complications, such as diabetic nephropathy, a chronic kidney disorder, can continue even after blood glucose normalization, suggesting a metabolic memory of the prior glycaemic state. 3. Dysregulation of epigenetic post-transcriptional modifications of histones in chromatin, including histone lysine methylation, has been implicated in aberrant gene regulation associated with the pathology of diabetes and its complications. Genome-wide studies have shown cell-type specific changes in histone methylation patterns under diabetic conditions. In addition, studies in vascular cells have shown long lasting changes in epigenetic modifications at key inflammatory gene promoters after prior exposure to diabetic conditions, suggesting a possible mechanism for metabolic memory. 4. Recent studies have shown roles for histone methylation, DNA methylation, as well as microRNA in diabetic nephropathy. Whether these epigenetic factors play a role in metabolic memory of diabetic kidney disease is less well understood. 5. The incidence of diabetes is growing rapidly, as also the cost of treating the resulting complications. A better understanding of metabolic memory and the potential involvement of epigenetic mechanisms in this phenomenon could enable the development of new therapeutic targets for the treatment and/or prevention of sustained diabetic complications.
    MeSH term(s) Animals ; Diabetes Complications/genetics ; Diabetes Complications/metabolism ; Diabetes Mellitus/genetics ; Diabetes Mellitus/metabolism ; Epigenomics ; Gene Expression Regulation ; Humans
    Language English
    Publishing date 2011-02-11
    Publishing country Australia
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 189277-0
    ISSN 1440-1681 ; 0305-1870 ; 0143-9294
    ISSN (online) 1440-1681
    ISSN 0305-1870 ; 0143-9294
    DOI 10.1111/j.1440-1681.2011.05497.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic db/db mice lead to increased inflammatory gene expression by targeting the histone methyltransferase Suv39h1.

    Villeneuve, Louisa M / Kato, Mitsuo / Reddy, Marpadga A / Wang, Mei / Lanting, Linda / Natarajan, Rama

    Diabetes

    2010  Volume 59, Issue 11, Page(s) 2904–2915

    Abstract: Objective: Diabetes remains a major risk factor for vascular complications that seem to persist even after achieving glycemic control, possibly due to "metabolic memory." Using cultured vascular smooth muscle cells (MVSMC) from type 2 diabetic db/db ... ...

    Abstract Objective: Diabetes remains a major risk factor for vascular complications that seem to persist even after achieving glycemic control, possibly due to "metabolic memory." Using cultured vascular smooth muscle cells (MVSMC) from type 2 diabetic db/db mice, we recently showed that decreased promoter occupancy of the chromatin histone H3 lysine-9 methyltransferase Suv39h1 and the associated repressive epigenetic mark histone H3 lysine-9 trimethylation (H3K9me3) play key roles in sustained inflammatory gene expression. Here we examined the role of microRNAs (miRs) in Suv39h1 regulation and function in MVSMC from diabetic mice.
    Research design and methods: We used luciferase assays with Suv39h1 3'untranslated region (UTR) reporter constructs and Western blotting of endogenous protein to verify that miR-125b targets Suv39h1. We examined the effects of Suv39h1 targeting on inflammatory gene expression by quantitative real time polymerase chain reaction (RT-qPCR), and H3K9me3 levels at their promoters by chromatin immunoprecipitation assays.
    Results: We observed significant upregulation of miR-125b with parallel downregulation of Suv39h1 protein (predicted miR-125b target) in MVSMC cultured from diabetic db/db mice relative to control db/+. miR-125b mimics inhibited both Suv39h1 3'UTR luciferase reporter activity and endogenous Suv39h1 protein levels. Conversely, miR-125b inhibitors showed opposite effects. Furthermore, miR-125b mimics increased expression of inflammatory genes, monocyte chemoattractant protein-1, and interleukin-6, and reduced H3K9me3 at their promoters in nondiabetic cells. Interestingly, miR-125b mimics increased monocyte binding to db/+ MVSMC toward that in db/db MVSMC, further imitating the proinflammatory diabetic phenotype. In addition, we found that the increase in miR-125b in db/db VSMC is caused by increased transcription of miR-125b-2.
    Conclusions: These results demonstrate a novel upstream role for miR-125b in the epigenetic regulation of inflammatory genes in MVSMC of db/db mice through downregulation of Suv39h1.
    MeSH term(s) 3' Untranslated Regions/genetics ; Animals ; Blotting, Western ; Diabetes Mellitus, Type 2/genetics ; Down-Regulation ; Gene Expression Regulation ; Gene Expression Regulation, Enzymologic ; Genes, Reporter ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase/genetics ; Humans ; Inflammation/genetics ; Inflammation/prevention & control ; Methyltransferases/genetics ; Mice ; MicroRNAs/genetics ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/physiopathology ; Promoter Regions, Genetic/genetics ; Repressor Proteins/genetics ; Up-Regulation
    Chemical Substances 3' Untranslated Regions ; MicroRNAs ; Repressor Proteins ; SUV39H1 protein, human (EC 2.1.1.) ; Histone Methyltransferases (EC 2.1.1.-) ; Methyltransferases (EC 2.1.1.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43)
    Language English
    Publishing date 2010-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db10-0208
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Natural regeneration potential and dynamics in boreal lichen woodlands of eastern Canada following soil scarification

    Charles Marty / Olivier Fradette / Louis Duchesne / Patrick Faubert / Rock Ouimet / Claude Villeneuve

    Frontiers in Forests and Global Change, Vol

    2023  Volume 6

    Abstract: ... Seedling density averaged ∼9 seedlings m–2 of exposed mineral soil and increased with seed tree mean ...

    Abstract Boreal lichen woodlands (LWs) are stable low tree-density zones of the Canadian boreal forest whose afforestation has been proposed as a way to create new C sinks and thus mitigate climate change. Planting operations in these remote areas are however costly and time-consuming, and may not be necessary when soil scarification is followed by dense natural regeneration. In the present study, we assessed the natural regeneration potential and dynamics in six boreal LWs of Québec, Canada, 11 years after soil scarification. The number, size (height and stem diameter) and age of seedlings were measured in 2-4 sampling plots per site (18 plots in total). Our data show that scarification operations produced on average 1,400 m2 ha–1 of exposed mineral soil (scarification intensity of 14%) with, however, a large within-site variability. The natural regeneration was mainly composed of black spruce seedlings (> 95%), averaged ∼12,000 seedlings ha–1 across the six sites and significantly varied among sites, mostly due to the variation in scarification intensity. Seedling density averaged ∼9 seedlings m–2 of exposed mineral soil and increased with seed tree mean diameter at breast height (DBH) (R2 = 0.51; P < 0.05) but not with the density of seed trees, revealing the importance of old and large seed trees in natural regeneration success. Together, scarification intensity and the DBH of remaining seed trees explained ∼60% of the variation in natural regeneration density across the 18 sampled plots. The rate of establishment of seedlings was generally high – with on average 60% of the carrying capacity of the substrate being reached within three years following scarification – and increased with seed tree mean DBH (R2 = 0.77; P < 0.05). However, the growth rate of seedlings was very low. Eleven years after scarification, 60% of the seedlings were < 15 cm and the height of 10-yr-old seedlings averaged 27.5 cm. Thus, even though seedling establishment was successful, the biomass accumulated by the natural regeneration ...
    Keywords boreal forest ; black spruce ; soil mechanical preparation ; scarification intensity ; natural sowing ; seed bed ; Forestry ; SD1-669.5 ; Environmental sciences ; GE1-350
    Subject code 580
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  7. Article: Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells.

    Kim, Daniel H / Villeneuve, Louisa M / Morris, Kevin V / Rossi, John J

    Nature structural & molecular biology

    2006  Volume 13, Issue 9, Page(s) 793–797

    Abstract: Argonaute proteins are the core components of effector complexes that facilitate RNA interference (RNAi). Small interfering RNAs (siRNAs) targeted to promoter regions mediate transcriptional gene silencing (TGS) in human cells through heterochromatin ... ...

    Abstract Argonaute proteins are the core components of effector complexes that facilitate RNA interference (RNAi). Small interfering RNAs (siRNAs) targeted to promoter regions mediate transcriptional gene silencing (TGS) in human cells through heterochromatin formation. RNAi effector complexes have yet to be implicated in the mechanism of mammalian TGS. Here we describe the role of the human Argonaute-1 homolog (AGO1) in directing TGS at the promoters for human immunodeficiency virus-1 coreceptor CCR5 and tumor suppressor RASSF1A. AGO1 associates with RNA polymerase II (RNAPII) and is required for histone H3 Lys9 dimethylation and TGS. AGO1, TAR RNA-binding protein-2 (7TRBP2) and Polycomb protein EZH2 colocalize to the siRNA-targeted RASSF1A promoter, implicating Polycomb silencing in the mechanism of mammalian TGS. These results establish a connection between RNAi components AGO1 and TRBP2, RNAPII transcription and Polycomb-regulated control of gene expression.
    MeSH term(s) Argonaute Proteins ; Cells, Cultured ; DNA Methylation ; DNA-Binding Proteins/metabolism ; Enhancer of Zeste Homolog 2 Protein ; Eukaryotic Initiation Factors/metabolism ; HeLa Cells ; Histones/metabolism ; Humans ; Phosphorylation ; Polycomb Repressive Complex 2 ; Polycomb-Group Proteins ; Promoter Regions, Genetic/genetics ; RNA Interference ; RNA Polymerase II/metabolism ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins/metabolism ; Receptors, CCR5/metabolism ; Repressor Proteins/metabolism ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/metabolism
    Chemical Substances AGO1 protein, human ; Argonaute Proteins ; DNA-Binding Proteins ; Eukaryotic Initiation Factors ; Histones ; Polycomb-Group Proteins ; RASSF1 protein, human ; RNA, Small Interfering ; RNA-Binding Proteins ; Receptors, CCR5 ; Repressor Proteins ; Transcription Factors ; Tumor Suppressor Proteins ; trans-activation responsive RNA-binding protein (136628-24-5) ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Polycomb Repressive Complex 2 (EC 2.1.1.43) ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2006-08-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/nsmb1142
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Role of the lysine-specific demethylase 1 in the proinflammatory phenotype of vascular smooth muscle cells of diabetic mice.

    Reddy, Marpadga A / Villeneuve, Louisa M / Wang, Mei / Lanting, Linda / Natarajan, Rama

    publication RETRACTED

    Circulation research

    2008  Volume 103, Issue 6, Page(s) 615–623

    Abstract: Insulin resistance and type 2 diabetes are major risk factors for vascular complications. Vascular smooth muscle cells (VSMCs) derived from db/db mice, an established mouse model of type 2 diabetes, displayed enhanced inflammatory gene expression and ... ...

    Abstract Insulin resistance and type 2 diabetes are major risk factors for vascular complications. Vascular smooth muscle cells (VSMCs) derived from db/db mice, an established mouse model of type 2 diabetes, displayed enhanced inflammatory gene expression and proatherogenic responses. We examined the hypothesis that aberrant epigenetic chromatin events may the underlying mechanism for this persistent dysfunctional behavior and "memory" of the diabetic cells. Chromatin immunoprecipitation assays showed that levels of histone H3 lysine 4 dimethylation (H3K4me2), a key chromatin mark associated with active gene expression, were significantly elevated at the promoters of the inflammatory genes monocyte chemoattractant protein-1 and interleukin-6 in db/db VSMCs relative to db/+ cells. Tumor necrosis factor-alpha-induced inflammatory gene expression, H3K4me2 levels, and recruitment of RNA polymerase II at the gene promoters were also enhanced in db/db VSMCs, demonstrating the formation of open chromatin poised for transcriptional activation in diabetes. On the other hand, protein levels of lysine-specific demethylase1 (LSD1), which negatively regulates H3K4 methylation and its occupancy at these gene promoters, were significantly reduced in db/db VSMCs. High glucose (25 mmol/L) treatment of human VSMCs also increased inflammatory genes with parallel increases in promoter H3K4me2 levels and reduced LSD1 recruitment. LSD1 gene silencing with small interfering RNAs significantly increased inflammatory gene expression and enhanced VSMC-monocyte binding in nondiabetic VSMCs. In contrast, overexpression of LSD1 in diabetic db/db VSMCs inhibited their enhanced inflammatory gene expression. These results demonstrate novel functional roles for LSD1 and H3K4 methylation in VSMCs and inflammation. Dysregulation of their actions may be a major mechanism for vascular inflammation and metabolic memory associated with diabetic complications.
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/enzymology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Histone Demethylases ; Histones/metabolism ; Humans ; Inflammation Mediators/physiology ; Lysine/metabolism ; Male ; Methylation ; Mice ; Mice, Knockout ; Mice, Mutant Strains ; Muscle, Smooth, Vascular/enzymology ; Muscle, Smooth, Vascular/pathology ; Myocytes, Smooth Muscle/enzymology ; Myocytes, Smooth Muscle/pathology ; Oxidoreductases, N-Demethylating/metabolism ; Oxidoreductases, N-Demethylating/physiology ; Phenotype
    Chemical Substances Histones ; Inflammation Mediators ; Histone Demethylases (EC 1.14.11.-) ; KDM1a protein, mouse (EC 1.14.11.-) ; Oxidoreductases, N-Demethylating (EC 1.5.-) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2008-08-07
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Retracted Publication
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.108.175190
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Characteristics of subjective cognitive decline associated with amyloid positivity.

    Janssen, Olin / Jansen, Willemijn J / Vos, Stephanie J B / Boada, Merce / Parnetti, Lucilla / Gabryelewicz, Tomasz / Fladby, Tormod / Molinuevo, José Luis / Villeneuve, Sylvia / Hort, Jakub / Epelbaum, Stéphane / Lleó, Alberto / Engelborghs, Sebastiaan / van der Flier, Wiesje M / Landau, Susan / Popp, Julius / Wallin, Anders / Scheltens, Philip / Rikkert, Marcel Olde /
    Snyder, Peter J / Rowe, Chris / Chételat, Gaël / Ruíz, Agustin / Marquié, Marta / Chipi, Elena / Wolfsgruber, Steffen / Heneka, Michael / Boecker, Henning / Peters, Oliver / Jarholm, Jonas / Rami, Lorena / Tort-Merino, Adrià / Binette, Alexa Pichet / Poirier, Judes / Rosa-Neto, Pedro / Cerman, Jiri / Dubois, Bruno / Teichmann, Marc / Alcolea, Daniel / Fortea, Juan / Sánchez-Saudinós, M Belén / Ebenau, Jarith / Pocnet, Cornelia / Eckerström, Marie / Thompson, Louisa / Villemagne, Victor / Buckley, Rachel / Burnham, Samantha / Delarue, Marion / Freund-Levi, Yvonne / Wallin, Åsa K / Ramakers, Inez / Tsolaki, Magda / Soininen, Hilkka / Hampel, Harald / Spiru, Luiza / Tijms, Betty / Ossenkoppele, Rik / Verhey, Frans R J / Jessen, Frank / Visser, Pieter Jelle

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2021  Volume 18, Issue 10, Page(s) 1832–1845

    Abstract: Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited.: Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the ... ...

    Abstract Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited.
    Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity.
    Results: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages.
    Discussion: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
    MeSH term(s) Humans ; Amyloid ; Amyloidogenic Proteins ; Amyloidosis ; Apolipoprotein E4/genetics ; Biomarkers ; Brain/metabolism ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/psychology ; Positron-Emission Tomography
    Chemical Substances Amyloid ; Amyloidogenic Proteins ; Apolipoprotein E4 ; Biomarkers
    Language English
    Publishing date 2021-12-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12512
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes.

    Villeneuve, Louisa M / Reddy, Marpadga A / Lanting, Linda L / Wang, Mei / Meng, Li / Natarajan, Rama

    Proceedings of the National Academy of Sciences of the United States of America

    2008  Volume 105, Issue 26, Page(s) 9047–9052

    Abstract: Diabetic patients continue to develop inflammation and vascular complications even after achieving glycemic control. This poorly understood "metabolic memory" phenomenon poses major challenges in treating diabetes. Recent studies demonstrate a link ... ...

    Abstract Diabetic patients continue to develop inflammation and vascular complications even after achieving glycemic control. This poorly understood "metabolic memory" phenomenon poses major challenges in treating diabetes. Recent studies demonstrate a link between epigenetic changes such as chromatin histone lysine methylation and gene expression. We hypothesized that H3 lysine-9 tri-methylation (H3K9me3), a key repressive and relatively stable epigenetic chromatin mark, may be involved in metabolic memory. This was tested in vascular smooth muscle cells (VSMC) derived from type 2 diabetic db/db mice. These cells exhibit a persistent atherogenic and inflammatory phenotype even after culture in vitro. ChIP assays showed that H3K9me3 levels were significantly decreased at the promoters of key inflammatory genes in cultured db/db VSMC relative to control db/+ cells. Immunoblotting demonstrated that protein levels of the H3K9me3 methyltransferase Suv39h1 were also reduced in db/db VSMC. Furthermore, db/db VSMC were hypersensitive to TNF-alpha inflammatory stimulus, which induced dramatic and sustained decreases in promoter H3K9me3 and Suv39h1 occupancy. Recruitment of corepressor HP1alpha was also reduced under these conditions in db/db cells. Overexpression of SUV39H1 in db/db VSMC reversed this diabetic phenotype. Conversely, gene silencing of SUV39H1 with shRNAs in normal human VSMC (HVSMC) increased inflammatory genes. HVSMC cultured in high glucose also showed increased inflammatory gene expression and decreased H3K9me3 at their promoters. These results demonstrate protective roles for H3K9me3 and Suv39h1 against the preactivated state of diabetic VSMC. Dysregulation of epigenetic histone modifications may be a major underlying mechanism for metabolic memory and sustained proinflammatory phenotype of diabetic cells.
    MeSH term(s) Animals ; Chromosomal Proteins, Non-Histone/metabolism ; Diabetes Mellitus/genetics ; Diabetes Mellitus/immunology ; Epigenesis, Genetic/drug effects ; Glucose/pharmacology ; Histones/metabolism ; Humans ; Immunologic Memory/drug effects ; Inflammation/genetics ; Lysine/metabolism ; Methylation/drug effects ; Methyltransferases/metabolism ; Mice ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/pathology ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/pathology ; Phenotype ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Repressor Proteins/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
    Chemical Substances Chromosomal Proteins, Non-Histone ; Histones ; Repressor Proteins ; Tumor Necrosis Factor-alpha ; heterochromatin-specific nonhistone chromosomal protein HP-1 (107283-02-3) ; SUV39H1 protein, human (EC 2.1.1.) ; Methyltransferases (EC 2.1.1.-) ; Glucose (IY9XDZ35W2) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2008-06-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0803623105
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top