scholarly journals Expression of IMP dehydrogenase in differentiating HL-60 cells

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 570-576 ◽  
Author(s):  
FR Collart ◽  
E Huberman
Keyword(s):  
Cell Differentiation ◽  
Mycophenolic Acid ◽  
Messenger Rna ◽  
Cellular Level ◽  
Imp Dehydrogenase ◽  
Protein Levels ◽  
Impdh Activity ◽  
Subsequent Decrease ◽  
Number Of Factors ◽  
Steady State Levels

Abstract Addition of mycophenolic acid to cultures of HL-60 cells results in a decreased cellular level of guanine nucleotides and the induction of cell differentiation. During the early stages of this induction, steady- state levels of cellular IMP dehydrogenase (IMPDH), messenger RNA (mRNA), and protein are increased, perhaps because of cellular compensation for the inhibition of IMPDH activity. The subsequent decrease in IMPH mRNA and protein levels after several days of treatment suggests a change in the control of IMPDH expression. In contrast to the pattern of increased IMPDH expression observed in the mycophenolic acid-treated cells, treatment of HL-60 cells with two other inducers of differentiation, namely retinoic acid and phorbol 12- myristate 13-acetate, resulted in stable or decreased levels of cellular IMPDH mRNA and protein. However, the kinetics of this expression were different. These results suggest that a number of factors influence the regulation of IMPDH expression during the induction of HL-60 cell differentiation, including the nature of the inducer. A decrease in the cellular IMPDH activity was observed for all of the inducers, suggesting that this decreased activity may be a determining factor in the acquisition of a mature phenotype in the HL- 60 cells.

scholarly journals Expression of IMP dehydrogenase in differentiating HL-60 cells

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 570-576
Author(s):  
FR Collart ◽  
E Huberman
Keyword(s):  
Cell Differentiation ◽  
Mycophenolic Acid ◽  
Messenger Rna ◽  
Cellular Level ◽  
Imp Dehydrogenase ◽  
Protein Levels ◽  
Impdh Activity ◽  
Subsequent Decrease ◽  
Number Of Factors ◽  
Steady State Levels

Addition of mycophenolic acid to cultures of HL-60 cells results in a decreased cellular level of guanine nucleotides and the induction of cell differentiation. During the early stages of this induction, steady- state levels of cellular IMP dehydrogenase (IMPDH), messenger RNA (mRNA), and protein are increased, perhaps because of cellular compensation for the inhibition of IMPDH activity. The subsequent decrease in IMPH mRNA and protein levels after several days of treatment suggests a change in the control of IMPDH expression. In contrast to the pattern of increased IMPDH expression observed in the mycophenolic acid-treated cells, treatment of HL-60 cells with two other inducers of differentiation, namely retinoic acid and phorbol 12- myristate 13-acetate, resulted in stable or decreased levels of cellular IMPDH mRNA and protein. However, the kinetics of this expression were different. These results suggest that a number of factors influence the regulation of IMPDH expression during the induction of HL-60 cell differentiation, including the nature of the inducer. A decrease in the cellular IMPDH activity was observed for all of the inducers, suggesting that this decreased activity may be a determining factor in the acquisition of a mature phenotype in the HL- 60 cells.

Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression by measuring IMP dehydrogenase activity

1995 ◽  
Vol 41 (2) ◽  
pp. 295-299 ◽  
Author(s):  
L J Langman ◽  
D F LeGatt ◽  
R W Yatscoff
Keyword(s):  
Enzyme Activity ◽  
Mycophenolic Acid ◽  
Whole Blood ◽  
De Novo ◽  
Immunosuppressive Drugs ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Imp Dehydrogenase ◽  
Impdh Activity ◽  
Key Enzyme

Abstract Pharmacodynamic monitoring of the biological effect of immunosuppressive drugs provides an alternative to traditional therapeutic drug monitoring. We chose this method to investigate mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by inhibition of IMP dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. Using an assay developed for measuring IMPDH activity in whole blood, we found the concentration of MPA required for 50% inhibition of enzyme activity to be in the range of 2.0-5.0 mg/L for both human and rabbit blood. The amount of enzyme activity in whole blood depended on the concentration of the leukocytes, was unaffected by the type of anticoagulant used, and was stable in blood specimens stored for as long as 48 h at 4 degrees C. An inverse relationship was found between plasma MPA concentrations and IMPDH activity in rabbits administered a single dose of RS-61443, the prodrug of MPA. Maximal inhibition of IMPDH activity (by approximately 60%) occurs at peak concentrations of MPA; as the concentration of the drug decreases postdose, the enzyme activity gradually increases with little or no inhibition being observed 24 h postdose.

scholarly journals Estrogen directly activates AID transcription and function

2009 ◽  
Vol 206 (1) ◽  
pp. 99-111 ◽  
Author(s):  
Siim Pauklin ◽  
Isora V. Sernández ◽  
Gudrun Bachmann ◽  
Almudena R. Ramiro ◽  
Svend K. Petersen-Mahrt
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Messenger Rna ◽  
Somatic Hypermutation ◽  
Cellular Level ◽  
Myc Oncogene ◽  
Protein Levels ◽  
Estrogen Response ◽  
Activation Induced Deaminase ◽  
And Function

The immunological targets of estrogen at the molecular, humoral, and cellular level have been well documented, as has estrogen's role in establishing a gender bias in autoimmunity and cancer. During a healthy immune response, activation-induced deaminase (AID) deaminates cytosines at immunoglobulin (Ig) loci, initiating somatic hypermutation (SHM) and class switch recombination (CSR). Protein levels of nuclear AID are tightly controlled, as unregulated expression can lead to alterations in the immune response. Furthermore, hyperactivation of AID outside the immune system leads to oncogenesis. Here, we demonstrate that the estrogen–estrogen receptor complex binds to the AID promoter, enhancing AID messenger RNA expression, leading to a direct increase in AID protein production and alterations in SHM and CSR at the Ig locus. Enhanced translocations of the c-myc oncogene showed that the genotoxicity of estrogen via AID production was not limited to the Ig locus. Outside of the immune system (e.g., breast and ovaries), estrogen induced AID expression by >20-fold. The estrogen response was also partially conserved within the DNA deaminase family (APOBEC3B, -3F, and -3G), and could be inhibited by tamoxifen, an estrogen antagonist. We therefore suggest that estrogen-induced autoimmunity and oncogenesis may be derived through AID-dependent DNA instability.

Synbiotic-associated improvement in liver function in cirrhotic patients: Relation to changes in circulating cytokine messenger RNA and protein levels

2007 ◽  
Vol 19 (1) ◽  
Author(s):  
Stephen M. Riordan ◽  
Narelle A. Skinner ◽  
Christopher J. Mciver ◽  
Qing Liu ◽  
Stig Bengmark ◽  
...  
Keyword(s):  
Liver Function ◽  
Messenger Rna ◽  
Protein Levels ◽  
Cirrhotic Patients

scholarly journals Changes in globin messenger RNA content during erythroid cell differentiation.

1975 ◽  
Vol 250 (15) ◽  
pp. 6054-6058
Author(s):  
F Ramirez ◽  
R Gambino ◽  
G M Maniatis ◽  
R A Rifkind ◽  
P A Marks ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Messenger Rna ◽  
Erythroid Cell ◽  
Rna Content ◽  
Erythroid Cell Differentiation

scholarly journals Role of a Stem-Loop Structure inHelicobacter pylori cagATranscript Stability

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
John T. Loh ◽  
Aung Soe Lin ◽  
Amber C. Beckett ◽  
Mark S. McClain ◽  
Timothy L. Cover
Keyword(s):  
Steady State ◽  
Untranslated Region ◽  
Loop Structure ◽  
Stem Loop ◽  
Content Type ◽  
Transcript Stability ◽  
Protein Levels ◽  
Caga Protein ◽  
Stem Loop Structure ◽  
Steady State Levels

ABSTRACTHelicobacter pyloriCagA is a secreted effector protein that contributes to gastric carcinogenesis. Previous studies showed that there is variation amongH. pyloristrains in the steady-state levels of CagA and that a strain-specific motif downstream of thecagAtranscriptional start site (the +59 motif) is associated with both high levels of CagA and premalignant gastric histology. ThecagA5′ untranslated region contains a predicted stem-loop-forming structure adjacent to the +59 motif. In the current study, we investigated the effect of the +59 motif and the adjacent stem-loop oncagAtranscript levels andcagAmRNA stability. Using site-directed mutagenesis, we found that mutations predicted to disrupt the stem-loop structure resulted in decreased steady-state levels of both thecagAtranscript and the CagA protein. Additionally, these mutations resulted in a decreasedcagAmRNA half-life. Mutagenesis of the +59 motif without altering the stem-loop structure resulted in reduced steady-statecagAtranscript and CagA protein levels but did not affectcagAtranscript stability.cagAtranscript stability was not affected by increased sodium chloride concentrations, an environmental factor known to augmentcagAtranscript levels and CagA protein levels. These results indicate that both a predicted stem-loop structure and a strain-specific +59 motif in thecagA5′ untranslated region influence the levels ofcagAexpression.

Lower antioxidant capacity in the prefrontal cortex of individuals with schizophrenia

2017 ◽  
Vol 52 (7) ◽  
pp. 690-698 ◽  
Author(s):  
Yiru Zhang ◽  
Vibeke Sørensen Catts ◽  
Cynthia Shannon Weickert
Keyword(s):  
Prefrontal Cortex ◽  
Antioxidant Capacity ◽  
Mrna Expression ◽  
Antioxidant System ◽  
Messenger Rna ◽  
Total Glutathione ◽  
Protein Levels ◽  
Significant Difference ◽  
Dorsolateral Prefrontal ◽  
And Control

Objective: The glutathione (GSH) pathway is the main antioxidant system to protect against oxidative stress in the human brain. In this study, we tested whether molecular components of the GSH antioxidant system are changed in dorsolateral prefrontal cortex tissue from people with schizophrenia compared to controls. Method: The levels of total glutathione and reduced GSH were determined by fluorometric assay via quantifying thiols in extracts from frontal cortex of 68 people. Immunoblotting was used to measure levels of enzymes responsible for maintaining GSH, the glutamyl-cysteine ligase (GCL) catalytic subunit (GCLC) and the GSH peroxidase (GPx)-like protein ( n = 74). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure GCLC messenger RNA (mRNA) expression. Results: Both total glutathione ( t(66) = 2.467, p = 0.016) and reduced GSH ( t(66) = 3.001, p = 0.004) levels were significantly less in people with schizophrenia than in controls. However, there were no significant differences in either GCLC-like protein ( t(72) = −1.077, p = 0.285) or GCLC mRNA expression ( t(71) = −0.376, p = 0.708) between people with schizophrenia and control subjects. There was also no significant difference of GPx-like protein levels between schizophrenia and controls ( t(72) = −0.060, p = 0.952). Moreover, no significant correlations of putative confounding factors with GSH changes were detected. Discussion: These results suggest that people with schizophrenia have impaired GSH antioxidant capacity, alongside normal levels of key regulatory proteins.

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