Implications of age and diet on canine cerebral cortex transcription

Swanson, Kelly S.; Vester, Brittany M.; Apanavicius, Carolyn J.; Kirby, Naomi A.; Schook, Lawrence B.

doi:10.1016/j.neurobiolaging.2007.10.017

Cited by 35 publications

(43 citation statements)

References 66 publications

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“…The fact that most gene expression differences were attributed to age in this experiment agrees with our previous experiments focused on gene expression in cerebral cortex [11], skeletal muscle [12], and abdominal adipose [13] tissues from these same dogs. Of the 14,217 genes expressed by colon mucosa, 1.49% (212/14,217) were significantly altered due to age.…”

Section: Resultssupporting

confidence: 91%

“…Our previous experiments also reported age as the primary factor affecting gene expression changes, with a small percentage of genes being altered. In short, only 0.25% of genes in adipose tissue [13], 2.91% of genes in skeletal muscle [12], and 6.48% of genes in cerebral cortex [11] were differentially expressed due to age. The small number of genes altered by age in this experiment is in agreement with previous microarray data from muscle [9], duodenum, and colon [16] tissues of aged vs. young mice.…”

Section: Resultsmentioning

confidence: 95%

“…Previously, we reported the effects of diet (APB; animal protein-based vs. PPB; plant protein-based) and age (young adult vs. senior dogs) on gene expression profiles of cerebral cortex [11], skeletal muscle [12], and abdominal adipose tissues [13]. To our knowledge, no large-scale molecular analysis of colonic mucosa in young adult vs. senior dogs is available.…”

Section: Introductionmentioning

confidence: 99%

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Gene Expression Profiles of Colonic Mucosa in Healthy Young Adult and Senior Dogs

et al. 2010

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BackgroundWe have previously reported the effects of age and diet on nutrient digestibility, intestinal morphology, and large intestinal fermentation patterns in healthy young adult and senior dogs. However, a genome-wide molecular analysis of colonic mucosa as a function of age and diet has not yet been performed in dogs.Methodology/Principal FindingsColonic mucosa samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed one of two diets (animal protein-based vs. plant protein-based) for 12 months. Total RNA in colonic mucosa was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Results indicated that the majority of gene expression changes were due to age (212 genes) rather than diet (66 genes). In particular, the colonic mucosa of senior dogs had increased expression of genes associated with cell proliferation, inflammation, stress response, and cellular metabolism, whereas the expression of genes associated with apoptosis and defensive mechanisms were decreased in senior vs. young adult dogs. No consistent diet-induced alterations in gene expression existed in both age groups, with the effects of diet being more pronounced in senior dogs than in young adult dogs.ConclusionOur results provide molecular insight pertaining to the aged canine colon and its predisposition to dysfunction and disease. Therefore, our data may aid in future research pertaining to age-associated gastrointestinal physiological changes and highlight potential targets for dietary intervention to limit their progression.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Gene Expression Profiles of Colonic Mucosa in Healthy Young Adult and Senior Dogs

et al. 2010

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“…These findings underline the potential decisive role of OCT in the development of neurodegenerative diseases. In this view, the interaction of LAPTM4A with OCT could be of importance, considering that, in brain of aged dogs, which develop similar neurological features as elderly humans, a significant upregulation of LAPTM4A-mRNA expression was found [31]. In the future, the role of the regulation of OCT expression and function by the interaction with LAPTM4A should be considered when investigating the role of dopaminergic signalling pathways in neurodegenerative diseases such as Parkinson's and Alzheimer's diseases.…”

Section: Discussionmentioning

confidence: 99%

LAPTM4A interacts with hOCT2 and regulates its endocytotic recruitment

Grabner

Brast

Sučić³

et al. 2011

Cell. Mol. Life Sci.

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Human organic cation transporter 2 (hOCT2) is involved in the transport of endogenous and exogenous organic cations mainly in cells of the kidney and the brain. Here, we focus on the regulation of hOCT2 by direct protein-protein interaction. Screening within a mating-based split-ubiquitin-yeast-two-hybrid system (mBSUS) revealed the lysosomal-associated protein transmembrane 4 alpha (LAPTM4A) as a potential interacting protein. Interaction of LAPTM4A and hOCT2 was confirmed by pulldown assays, FRET microscopy analysis and immunofluorescence microscopy. Functionally, overexpression of LAPTM4A significantly decreased ASP(+) uptake in HEK293 cells stably transfected with hOCT2, suggesting a negative regulation of hOCT2-mediated transport. Furthermore, overexpression of LAPTM4A leads to a significantly decreased hOCT2 plasma membrane expression in surface biotinylation experiments. In addition, significant expression of LAPTM4A in human kidney was demonstrated by immunoblotting and immunofluorescence.In this work, LAPTM4A has been identified as interaction partner of hOCT2. LAPTM4A regulates the function of hOCT2 by influencing its trafficking to/from the cell membrane and processing it via the intracellular sorting machinery.

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“…cDNAs were then synthesized using Superscript III kits (Invitrogen); hybridization of the samples with Affymetrix mouse arrays was then performed at the Harvard Medical School Facility according to the manufacturer’s protocol. The procedures for microarray data analyses were described previously by Swanson et al (2009).…”

Section: Methodsmentioning

confidence: 99%

OX40 Costimulation Inhibits Foxp3 Expression and Treg Induction via BATF3-Dependent and Independent Mechanisms

et al. 2018

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SUMMARY Naive CD4+ T cells can be converted to Foxp3+ T regulatory cells (Tregs) in the periphery (iTregs), where induction of Foxp3 gene expression is central to Treg differentiation. OX40 signaling is known to inhibit Foxp3 expression and Treg induction, but the underlying mechanisms remain poorly defined. Here, we found that OX40 costimulation activates two distinct molecular pathways to suppress Foxp3 expression in freshly activated naive CD4+ T cells. Specifically, OX40 upregulates BATF3 and BATF, which produce a closed chromatin configuration to repress Foxp3 expression in a Sirt1/7-dependent manner. Moreover, OX40 can also activate the AKT-mTOR pathway, especially in the absence of BATF3 and BATF, to inhibit Foxp3 induction, and this is mediated by phos-phorylation and nuclear exclusion of the transcription factor Foxo1. Taken together, our results provide key mechanistic insights into how OX40 inhibits Foxp3 expression and Treg induction in the periphery.

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Implications of age and diet on canine cerebral cortex transcription

Cited by 35 publications

References 66 publications

Gene Expression Profiles of Colonic Mucosa in Healthy Young Adult and Senior Dogs

Gene Expression Profiles of Colonic Mucosa in Healthy Young Adult and Senior Dogs

LAPTM4A interacts with hOCT2 and regulates its endocytotic recruitment

OX40 Costimulation Inhibits Foxp3 Expression and Treg Induction via BATF3-Dependent and Independent Mechanisms

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