Temporal pattern of rat small intestinal gene expression with refeeding

1994 ◽  
Vol 266 (1) ◽  
pp. G83-G89 ◽  
Author(s):  
R. A. Hodin ◽  
J. R. Graham ◽  
S. Meng ◽  
M. P. Upton
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Early Response ◽  
Protein Synthesis Inhibitor ◽  
Chow Diet ◽  
Intestinal Alkaline Phosphatase ◽  
Synthesis Inhibitor ◽  
Adult Rats ◽  
Fed State ◽  
Small Intestinal

Studies were carried out to elucidate the molecular mechanisms underlying small intestinal epithelial growth. Adult rats were fasted for 4 days and then refed a chow diet for up to 48 h. Histological examination confirmed the sequential occurrence of mucosal atrophy and hyperplasia. Northern blot analyses of RNA derived from small intestinal mucosal scrapings revealed a striking pattern of alterations in the expression of two different categories of genes. There were very early increases in the expression of c-fos and c-jun, reflecting the mitogenic response to refeeding that occurs within the crypt compartment. Studies using the protein synthesis inhibitor cycloheximide suggest that c-fos and c-jun are part of the “immediate-early” response of the small intestine. At later time points after the refeeding stimulus, differential changes occurred in the expression of the brush-border enzymes, lactase, and intestinal alkaline phosphatase (IAP). Refeeding caused a decrease in lactase gene expression and an increase in the expression of the 3.0-kb IAP mRNA species, reflecting a return of the villus phenotype to the normal fed state. Thus we have demonstrated a complex and temporally related pattern of gene expression within the small intestinal epithelium upon refeeding. The results provide insight into the relationship between the processes of intestinal growth and differentiation.

Gene expression responses over 24 h to lengthening and shortening contractions in human muscle: major changes in CSRP3, MUSTN1, SIX1, and FBXO32

2007 ◽  
Vol 31 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Matthew C. Kostek ◽  
Yi-Wen Chen ◽  
Daniel J. Cuthbertson ◽  
Rongye Shi ◽  
Mark J. Fedele ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Muscle Size ◽  
Temporal Expression ◽  
Lengthening Contractions ◽  
Fed State ◽  
Custom Made ◽  
Physiological Adaptations ◽  
Shortening Contractions

Resistance training using lengthening (eccentric) contractions induces greater increases in muscle size than shortening (concentric) contractions, but the underlying molecular mechanisms are not clear. Using temporal expression profiling, we compared changes in gene expression within 24 h of an acute bout of each type of contractions conducted simultaneously in the quadriceps of different legs. Five healthy young men performed shortening contractions with one leg while the contralateral leg performed lengthening contractions. Biopsies were taken from both legs before exercise and 3, 6, and 24 h afterwards, in the fed state. Expression profiling ( n = 3) was performed using a custom-made Affymetrix MuscleChip containing probe sets of ∼3,300 known genes and expressed sequence tags expressed in skeletal muscle. We identified 51 transcripts differentially regulated between the two exercise modes. Using unsupervised hierarchical clustering, we identified four distinct clusters, three of which corresponded to unique functional categories (protein synthesis, stress response/early growth, and sarcolemmal structure). Using quantitative RT-PCR ( n = 5), we verified expression changes (lengthening/shortening) in SIX1 (3 h, −1.9-fold, P < 0.001), CSRP3 (6 h, 2.9-fold, P < 0.05), and MUSTN1 (24 h, 4.3-fold, P < 0.05). We examined whether FBXO32/atrogin-1/MAFbx, a known regulator of protein breakdown and of muscle atrophy was differentially expressed: the gene was downregulated after lengthening contractions (3 h, 2.7-fold, P < 0.05; 6 h, 3.3-fold, P < 0.05; 24 h, 2.3-fold, P < 0.05). The results suggested that lengthening and shortening contractions activated distinct molecular pathways as early as 3 h postexercise. The molecular differences might contribute to mechanisms underlying the physiological adaptations seen with training using the two modes of exercise.

Tri-iodothyronine and cycloheximide enhance insulin-like growth factor-binding protein-1 gene expression in human hepatoma cells

1993 ◽  
Vol 10 (1) ◽  
pp. 7-13 ◽  
Author(s):  
M Angervo ◽  
P Leinonen ◽  
R Koistinen ◽  
M Julkunen ◽  
M Seppälä
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Hepatoma Cells ◽  
Protein Synthesis Inhibitor ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Synthesis Inhibitor ◽  
Genes Encoding ◽  
Protein Mediator

ABSTRACT The growth-regulating actions of IGFs are modulated by their binding proteins (IGFBPs). The serum concentration of IGFBP-1 is down-regulated by insulin, and in-vitro studies have demonstrated that IGFBP-1 secretion from various tissues and cells can be stimulated by theophylline, forskolin, oestrogen and progesterone. We have studied the effects and mechanisms of thyroid hormone action on IGFBP-1 gene expression and secretion by human hepatoma cells in vitro. Tri-iodothyronine dose-dependently enhanced IGFBP-1 secretion in serum-free HepG2 cell cultures after 24–48 h of exposure, as measured by a specific immunofluorometric assay. This was accompanied by an increase (+ 50%) in the amount of IGFBP-1 mRNA, which could be prevented by cycloheximide, a protein synthesis inhibitor. Cycloheximide transiently enhanced (+ 200%) the accumulation of IGFBP-1 mRNA at 3–12 h of incubation, when no effect of tri-iodothyronine was observed. It is concluded that thyroid hormone stimulates IGFBP-1 secretion slowly by enhancing IGFBP-1 gene expression by a protein mediator. The acute stimulation of IGFBP-1 gene transcription by cycloheximide associates this gene with a number of growth-related genes encoding growth- and tumour-associated peptides.

scholarly journals Western-diet consumption induces alteration of barrier function mechanisms in the ileum that correlates with metabolic endotoxemia in rats

2017 ◽  
Vol 313 (2) ◽  
pp. E107-E120 ◽  
Author(s):  
Mathilde Guerville ◽  
Anaïs Leroy ◽  
Annaëlle Sinquin ◽  
Fabienne Laugerette ◽  
Marie-Caroline Michalski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Elevated Serum ◽  
Caloric Intake ◽  
Western Diet ◽  
Chow Diet ◽  
Low Grade ◽  
Mrna Levels ◽  
Intestinal Alkaline Phosphatase ◽  
Ad Libitum ◽  
Metabolic Endotoxemia

Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and -β gene expression along with high ileal permeability to LPS were observed in WD compared with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD-fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepatic aoah gene expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment induced by WD feeding contribute to metabolic endotoxemia.

scholarly journals Hepatic Gene Expression Changes in Hypothyroid Juvenile Mice: Characterization of a Novel Negative Thyroid-Responsive Element

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3932-3940 ◽  
Author(s):  
Hongyan Dong ◽  
Carole L. Yauk ◽  
Andrew Williams ◽  
Alice Lee ◽  
George R. Douglas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Microarrays ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Transient Gene Expression ◽  
Early Response ◽  
Response Element ◽  
Gene Expression Studies ◽  
Maternal Thyroid ◽  
Responsive Element

The molecular mechanisms involved in the response of developing mice to disruptions in maternal thyroid hormone (TH) homeostasis are poorly characterized. We used DNA microarrays to examine a broad spectrum of genes from the livers of mice rendered hypothyroid by treating pregnant mice from gestational d 13 to postnatal d 15 with 6-propyl-2-thiouracil in drinking water. Twenty-four individuals (one male and one female pup from six litters of control or 6-propyl-2-thiouracil treatment groups, respectively) were profiled using Agilent oligonucleotide microarrays. MAANOVA identified 96 differentially expressed genes (false discovery rate adjusted P &lt; 0.1 and fold change &gt; 2 in at least one gender). Of these, 72 genes encode proteins of known function, 15 of which had previously been identified as regulated by TH. Pathway analysis revealed these genes are involved in metabolism, development, cell proliferation, apoptosis, and signal transduction. An immediate-early response gene, Nr4a1 (nuclear receptor subfamily 4, group A, member 1), was up-regulated by 3-fold in hypothyroid juvenile mouse liver; treatment of HepG2 cells with T3 resulted in down-regulation of Nr4a1. A potential thyroid response element −1218 to −1188 bp upstream of the promoter region of Nr4a1 was identified and demonstrated to bind TH receptor (TR)-α and TRβ. Point mutation or deletion of the sequence containing the potential Nr4a1-thyroid response element in transient gene expression studies resulted in both higher basal expression and loss of T3 regulatory capacity, suggesting that this site is responsible for the negative regulation of gene expression by TR and TH.

High affinity promoter binding of STOP1 is essential for the early aluminum-inducible expression of novel Al resistance genes GDH1 and GDH2 in Arabidopsis

2021 ◽  
Author(s):  
Mutsutomo Tokizawa ◽  
Takuo Enomoto ◽  
Hiroki Ito ◽  
Liujie Wu ◽  
Yuriko Kobayashi ◽  
...  
Keyword(s):  
Binding Site ◽  
Resistance Genes ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Aluminum Toxicity ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Induced Expression ◽  
Aluminum Resistance ◽  
High Affinity

Abstract Malate-efflux from roots, which is regulated by the transcription factor STOP1 (SENSITIVE-TO-PROTON-RHIZOTOXICITY1), which mediates aluminum-induced expression of ALUMINUM-ACTIVATED-MALATE-TRANSPORTER1 (AtALMT1), is critical for aluminum-resistance in Arabidopsis thaliana. Several studies showed that root AtALMT1 expression is rapidly observed in response to aluminum (within 1-hour), this early induction is an important mechanism to immediately protect roots from aluminum-toxicity. Additionally, identifying the molecular mechanisms that underlie rapid aluminum-resistance responses should lead to a better understanding of plant aluminum-sensing and -signal transduction mechanisms. In this study, histochemical analyses using GFP-tagged STOP1 proteins showed that STOP1 proteins were accumulated in the nucleus soon after aluminum-treatment. The rapid aluminum-induced STOP1-nuclear localization and AtALMT1-induction were observed in the presence of the protein synthesis inhibitor, suggesting that post-translational regulation is involved in these events. STOP1 also regulated rapid aluminum-induced expression for other genes that carry a functional/high-affinity STOP1-binding site in their promoter, including STOP2, GLUTAMATE-DEHYDROGENASE1 and 2 (GDH1 and 2), but not for Al resistance genes which have no functional STOP1-binding site such as ALUMINUM-SENSITIVE3, suggesting that the binding of STOP1 in the promoter is essential for the early induction. Finally, we report that GDH1 and 2 which are the target of STOP1 are novel aluminum-resistance genes in Arabidopsis.

Transcriptional and posttranscriptional regulation of CSF-1 gene expression in human monocytes

1988 ◽  
Vol 8 (9) ◽  
pp. 3951-3954
Author(s):  
J Horiguchi ◽  
E Sariban ◽  
D Kufe
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Gene Transcription ◽  
Posttranscriptional Regulation ◽  
Drug Exposure ◽  
Actinomycin D ◽  
Protein Synthesis Inhibitor ◽  
Mrna Levels ◽  
Human Monocytes ◽  
Synthesis Inhibitor

Regulation of CSF-1 gene expression was investigated in human monocytes. CSF-1 transcripts were at low or undetectable levels in resting monocytes. However, in monocytes treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), CSF-1 mRNA was increased by 3 h and reached maximal levels by 12 h of drug exposure. When nuclear run-on assays were used, CSF-1 gene transcription was also at low or undetectable levels in resting monocytes but was activated after TPA exposure. TPA-treated monocytes exposed to actinomycin D further demonstrated that the half-life of the CSF-1 mRNA is 0.9 h. The results also demonstrated that the protein synthesis inhibitor, cycloheximide (CHX), increases CSF-1 mRNA levels in both resting and TPA-treated monocytes. These effects of CHX occurred in the absence of detectable increases in CSF-1 gene transcription. Moreover, treatment of monocytes with CHX and actinomycin D demonstrated that inhibition of protein synthesis is associated with stabilization of the CSF-1 transcript. Taken together, these findings indicated that CSF-1 gene expression is controlled at both transcriptional and posttranscriptional levels in human monocytes.

scholarly journals Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes

2011 ◽  
Vol 300 (3) ◽  
pp. G425-G432 ◽  
Author(s):  
Lei Lu ◽  
Tiantian Li ◽  
Graham Williams ◽  
Elizabeth Petit ◽  
Mark Borowsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Molecular Mechanisms ◽  
Cell Maturation ◽  
Epithelial Cell Line ◽  
Intestinal Epithelial ◽  
Tight Junction Formation ◽  
Expression Of Genes ◽  
Small Intestinal

It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC), including an increased expression of digestive hydrolases. However, the molecular mechanisms are not well understood, particularly in the human gut. Here we report a microarray analysis of HC-induced changes in gene expression in H4 cells (a well-characterized human fetal small intestinal epithelial cell line). This study identified a large number of HC-regulated genes, some involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication. HC also regulates the expression of genes important for cell maturation such as development of cell polarity, tight junction formation, and interactions with extracellular matrices. Using human small intestinal xenografts, we also show that HC can regulate the expression of genes important for intestinal epithelial cell maturation. Our dataset may serve as a useful resource for understanding and dissecting the molecular mechanisms of intestinal epithelial cell maturation.

scholarly journals Tissue-Specific Difference in the Molecular Mechanisms for the Development of Acute Insulin Resistance after Injury

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 24-32 ◽  
Author(s):  
Li Li ◽  
LaWanda H. Thompson ◽  
Ling Zhao ◽  
Joseph L. Messina
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Rapid Development ◽  
Serine Phosphorylation ◽  
Synthesis Inhibitor ◽  
Adult Rats ◽  
Counterregulatory Hormones

Acute insulin resistance occurs after injury, hemorrhage, infection, and critical illness. However, little is known about the development of this acute insulin-resistant state. In the current study, we found that insulin resistance develops rapidly in skeletal muscle, with the earliest insulin signaling defects at 60 min. However, defects in insulin signaling were measurable even earlier in liver, by as soon as 15 min after hemorrhage. To begin to understand the mechanisms for the development of acute insulin resistance, serine phosphorylation of insulin receptor substrate (IRS)-1 and c-Jun N-terminal kinase phosphorylation/activation was investigated. These markers (and possible contributors) of insulin resistance were increased in the liver after hemorrhage but not measurable in skeletal muscle. Because glucocorticoids are important counterregulatory hormones responsible for glucose homeostasis, a glucocorticoid synthesis inhibitor, metyrapone, and a glucocorticoid receptor antagonist, RU486, were administered to adult rats prior to hemorrhage. In the liver, the defects of insulin signaling after hemorrhage, including reduced tyrosine phosphorylation of the insulin receptor and IRS-1, association between IRS-1 and phosphatidylinositol 3-kinase and serine phosphorylation of Akt in response to insulin were not altered by pretreatment of rats with metyrapone or RU486. In contrast, hemorrhage-induced defects in insulin signaling were dramatically reversed in skeletal muscle, indicating a prevention of insulin resistance in muscle. These results suggest that distinct mechanisms for hemorrhage-induced acute insulin resistance are present in these two tissues and that glucocorticoids are involved in the rapid development of insulin resistance in skeletal muscle, but not in the liver, after hemorrhage. Glucocorticoids play a major role in the development of acute insulin resistance following hemorrhage in skeletal muscle, but not in the liver.

scholarly journals Epigenetic regulation of protein translation in KMT2A-rearranged AML

2019 ◽  
Author(s):  
Alexandra Lenard ◽  
Hongbo Michael Xie ◽  
Simone S. Riedel ◽  
Zuo-Fei Yuan ◽  
Nan Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Agent ◽  
Protein Translation ◽  
Ribosomal Gene ◽  
Clinical Activity ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Methyl Transferase ◽  
Antagonistic Effects ◽  
Translation Inhibitor

ABSTRACTInhibition of the histone methyl-transferase DOT1L (KMT4) has shown encouraging activity in preclinical models of KMT2A (MLL)-rearranged leukemia. The DOT1L inhibitor pinometostat (EPZ5676) was well tolerated in early phase clinical trials and showed modest clinical activity, including occasional complete responses (CRs) as single agent. These studies support the development of combinatorial therapies for KMT2A-rearranged leukemias. Here, we investigated two novel combinations: dual inhibition of the histone methyltransferases DOT1L and EZH2, and the combination of a DOT1L inhibitor with the protein synthesis inhibitor homoharringtonine (HHR).EZH2 is the catalytic histone methyltransferase in the polycomb repressive complex 2 (PRC2), and inhibition of EZH2 has reported preclinical activity in KMT2A-rearranged leukemia. We found that the H3K79 and H3K27 methyl marks are not dependent on each other, and that DOT1L and EZH2 inhibition affect largely distinct gene expression programs. In particular, the KMT2A/DOT1L target HOXA9, which is commonly de-repressed as a consequence of PRC2 loss or inhibition in other contexts, was not re-activated upon dual DOT1L/EZH2 knockout or inhibition. Despite encouraging data in murine KMT2A-MLLT3 transformed cells suggesting synergy between DOT1L and EZH2 inhibition, we found both synergistic and antagonistic effects on a panel of human KMT2A rearranged cell lines. Combinatorial inhibition of DOT1L and EZH2 is thus not a promising strategy. We identified opposing effects on ribosomal gene transcription and protein translation by DOT1L and EZH2 as a mechanism that is partially responsible for observed antagonistic effects. The effects of DOT1L inhibition on ribosomal gene expression prompted us to evaluate the combination of EPZ5676 with a protein translation inhibitor. EPZ5676 was synergistic with the protein translation inhibitor homoharringtonine (HHR), supporting further preclinical/clinical development of this combination.

Acute metabolic acidosis inhibits the induction of osteoblastic egr-1 and type 1 collagen

1997 ◽  
Vol 272 (5) ◽  
pp. C1450-C1456 ◽  
Author(s):  
K. K. Frick ◽  
L. Jiang ◽  
D. A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Bone Cells ◽  
Early Response ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Calvarial Bone ◽  
Ph Dependency ◽  
Medium Change ◽  
External Ph

Metabolic acidosis induces net calcium efflux from bone through a decrease in osteoblastic formation and an increase in osteoclastic resorption. We tested the hypothesis that changes in external pH would alter the expression of genes critical to the function of mouse calvarial bone cells, predominantly osteoblasts. Cells were cultured in physiologically neutral pH medium until confluent and then stimulated with fresh medium at either neutral or acidic pH. Among a group of immediate early response genes, including egr-1, junB, c-jun, junD, and c-fos, only egr-1 stimulation was modulated by changes in medium pH. At pH 7.4, RNA for egr-1 was stimulated approximately 10- to 30-fold, 40 min after medium change. A progressive decrease in pH to 6.8 led to a parallel reduction in egr-1 stimulation, and an increase in pH to 7.6 led to an increase in egr-1 stimulation. The protein synthesis inhibitor cycloheximide led to a superinduction of egr-1 with preservation of the pH dependency of expression. Osteoblasts synthesize collagen, which is subsequently mineralized. RNA for type 1 collagen was stimulated approximately three- to fivefold, 40 min after medium change. Again the stimulation was inhibited by acidosis and increased by alkalosis. Cycloheximide abolished the pH dependency of expression. These results suggest that small changes in external pH have a significant effect on the expression of certain genes important for osteoblastic function.

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