Differential regulation of G protein expression in rat hearts exposed to chronic hypoxia

1995 ◽  
Vol 269 (6) ◽  
pp. H1865-H1873 ◽  
Author(s):  
R. Kacimi ◽  
J. M. Moalic ◽  
A. Aldashev ◽  
D. E. Vatner ◽  
J. P. Richalet ◽  
...  
Keyword(s):  
Gene Expression ◽  
G Protein ◽  
Functional Activity ◽  
Protein Level ◽  
Chronic Hypoxia ◽  
Mrna Level ◽  
Mrna Levels ◽  
Protein Levels ◽  
Rat Hearts ◽  
And Function

Chronic hypoxia impairs adrenergic responsiveness. A modulation of Gs and/or G1 protein alpha-subunits may be associated with the downregulation of the beta-adrenergic receptors previously found in chronic hypoxia. G protein gene expression and protein level and function in rat hearts exposed to a 30-day hypobaric chronic hypoxia were compared with control rat hearts. No change was observed in G alpha s mRNA levels in either right or left ventricles. In right ventricles, mRNA levels of G alpha i-2 increased by 40% (P < 0.05), but not in left ventricles. In both left and right ventricles, chronic hypoxia did not modify G alpha i-2 and G alpha s protein amounts, but significantly decreased functional activity of G alpha s. In conclusion, gene expression, protein levels of G alpha s and G alpha i-2, and activity of G alpha s do not change in parallel fashion with chronic hypoxia. In chronic hypoxic right ventricles, although the mRNA level of G alpha i-2 is increased, the protein level is unchanged. One potential mechanism of desensitization to catecholamines in chronic hypoxia appears to involve a decreased functional activity of G alpha s in spite of normal mRNA and protein levels

scholarly journals Treatment with PPARαAgonist Clofibrate Inhibits the Transcription and Activation of SREBPs and Reduces Triglyceride and Cholesterol Levels in Liver of Broiler Chickens

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lijun Zhang ◽  
Chunyan Li ◽  
Fang Wang ◽  
Shenghua Zhou ◽  
Mingjun Shangguan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Broiler Chickens ◽  
Target Genes ◽  
Nuclear Protein ◽  
Mrna Level ◽  
Control Group ◽  
Mrna Levels ◽  
Protein Levels ◽  
Cholesterol Levels ◽  
Regulation Mechanisms

PPARαagonist clofibrate reduces cholesterol and fatty acid concentrations in rodent liver by an inhibition of SREBP-dependent gene expression. In present study we investigated the regulation mechanisms of the triglyceride- and cholesterol-lowering effect of the PPARαagonist clofibrate in broiler chickens. We observed that PPARαagonist clofibrate decreases the mRNA and protein levels of LXRαand the mRNA and both precursor and nuclear protein levels of SREBP1 and SREBP2 as well as the mRNA levels of the SREBP1 (FASNandGPAM) and SREBP2 (HMGCRandLDLR) target genes in the liver of treated broiler chickens compared to control group, whereas the mRNA level ofINSIG2, which inhibits SREBP activation, was increased in the liver of treated broiler chickens compared to control group. Taken together, the effects of PPARαagonist clofibrate on lipid metabolism in liver of broiler chickens involve inhibiting transcription and activation of SREBPs and SREBP-dependent lipogenic and cholesterologenic gene expression, thereby resulting in a reduction of the triglyceride and cholesterol levels in liver of broiler chickens.

scholarly journals Levels of G-proteins in liver and brain of lean and obese (ob/ob) mice

1992 ◽  
Vol 282 (1) ◽  
pp. 15-23 ◽  
Author(s):  
N McFarlane-Anderson ◽  
J Bailly ◽  
N Bégin-Heick
Keyword(s):  
Gene Expression ◽  
G Proteins ◽  
Protein Level ◽  
Mrna Level ◽  
Beta Subunits ◽  
Obese Mice ◽  
Protein Levels ◽  
Alpha Subunits ◽  
Brain Membranes ◽  
Liver Membranes

G-protein levels were assessed in liver and brain membranes of lean and obese mice. ADP-ribosylation and immunodetection studies revealed a decrease in the abundance of Gs and Gi alpha-subunits in the liver membranes of obese mice compared with lean mice. In contrast, in brain membranes, the abundance of these proteins was not significantly different between lean and obese mice. Studies at the mRNA level in both liver and brain revealed no difference in gene expression between lean and obese mice. Protein and mRNA studies both showed that Gs, Gi alpha 1, Gi alpha 2, Go alpha and G beta subunits are present in brain membranes, and Gi alpha 3 is barely detectable. In liver, Ga alpha, Gi alpha 2 and G beta subunits are the major constituents, whereas Gi alpha 1, Gi alpha 3 and Go alpha are barely detectable. It is possible that the differences observed at the protein level are due to different rates of translation of the mRNA. Different rates of release of the alpha-subunits from the membrane and/or different rates of degradation would also explain these results.

Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery

2005 ◽  
Vol 288 (6) ◽  
pp. L1049-L1058 ◽  
Author(s):  
Jian Wang ◽  
Letitia Weigand ◽  
Wenqian Wang ◽  
J. T. Sylvester ◽  
Larissa A. Shimoda
Keyword(s):  
Gene Expression ◽  
Pulmonary Artery ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Mrna Levels ◽  
Protein Levels ◽  
Kv Channel ◽  
Channel Gene ◽  
Pulmonary Arterial ◽  
Α Subunits

In pulmonary arterial smooth muscle cells (PASMCs), voltage-gated K+ (Kv) channels play an important role in regulating membrane potential, cytoplasmic free Ca2+ concentration, and pulmonary vasomotor tone. Previous studies demonstrated that exposure of rats to chronic hypoxia decreased Kv channel function in PASMCs from distal pulmonary arteries (dPA). To determine whether this decrease in function was due to decreased expression of Kv channel proteins and which Kv proteins might be involved, we analyzed Kv channel gene expression in intact, endothelium-denuded dPAs obtained from rats exposed to 10% O2 for 3 wk. Kv1.1, Kv1.2, Kv1.4, Kv1.5, Kv1.6, Kv2.1, Kv3.1, Kv4.3, and Kv9.3 channel α-subunits and Kv1, Kv2, and Kv3 β-subunits were expressed in rat dPAs. Exposure to chronic hypoxia decreased mRNA and protein levels of Kv1.1, Kv1.5, Kv1.6, Kv2.1, and Kv4.3 α-subunits in dPAs but did not alter gene or protein expression of these channels in aorta. Furthermore, chronic hypoxia did not alter the mRNA levels of β-subunits in dPAs. These results suggest that diminished transcription of Kv α-subunits may reduce the number of functional Kv channels in dPAs during prolonged hypoxia, causing the decreased Kv current previously observed in PASMCs and leading to pulmonary artery vasoconstriction.

scholarly journals Alcohol Metabolism in the Progression of Human Nonalcoholic Steatohepatitis

2018 ◽  
Vol 164 (2) ◽  
pp. 428-438 ◽  
Author(s):  
Hui Li ◽  
Erica Toth ◽  
Nathan J Cherrington
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Protein Level ◽  
Mrna Levels ◽  
Alcohol Metabolism ◽  
Aldh Activity ◽  
Nonalcoholic Fatty Liver ◽  
Protein Levels ◽  
Protein Adduct ◽  
And Function ◽  
Adh Activity

Abstract Alcohol metabolism is a well-characterized biological process that is dominated by the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) families. Nonalcoholic steatohepatitis (NASH) is the advanced inflammatory stage of nonalcoholic fatty liver disease (NAFLD) and is known to alter the metabolism and disposition of numerous drugs. The purpose of this study was to investigate the alterations in alcohol metabolism processes in response to human NASH progression. Expression and function of ADHs, ALDHs, and catalase were examined in normal, steatosis, NASH (fatty) and NASH (not fatty) human liver samples. ALDH4A1 mRNA was significantly decreased in both NASH groups, while no significant changes were observed in the mRNA levels of other alcohol-related enzymes. The protein levels of ADH1A, ADH1B, and ADH4 were each decreased in the NASH groups, which was consistent with a decreased overall ADH activity. The protein level of ALDH2 was significantly increased in both NASH groups, while ALDH1A1 and ALDH1B1 were only decreased in NASH (fatty) samples. ALDH activity represented by oxidation of acetaldehyde was decreased in the NASH (fatty) group. The protein level of catalase was decreased in both NASH groups, though activity was unchanged. Furthermore, the significant accumulation of 4-hydroxynonenal protein adduct in NASH indicated significant oxidative stress and a potential reduction in ALDH activity. Collectively, ADH and ALDH expression and function are profoundly altered in the progression of NASH, which may have a notable impact on ADH- and ALDH-associated cellular metabolism processes and lead to significant alterations in drug metabolism mediated by these enzymes.

scholarly journals Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16

2003 ◽  
Vol 30 (2) ◽  
pp. 253-262 ◽  
Author(s):  
M Imae ◽  
Z Fu ◽  
A Yoshida ◽  
T Noguchi ◽  
H Kato
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Fold Increase ◽  
Mrna Levels ◽  
Hormonal Factors ◽  
Protein Levels ◽  
Nuclear Exclusion ◽  
Protein Free Diet

Transcription factors of the FoxO family in mammals are orthologues of the Caenorhabditis elegans forkhead factor DAF-16, which has been characterized as a target of insulin-like signalling. Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. A number of in vitro studies have revealed that FoxOs are regulated through phosphorylation in response to insulin and related growth factors, resulting in their nuclear exclusion and inactivation. To clarify the mechanisms involved in the regulation of these factors in vivo, we investigated in the present study whether or not, and if so how, their mRNA levels in rat liver respond to the stimuli of several nutritional and hormonal factors. Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. Of the three FoxO genes, FoxO4 only showed altered levels of mRNA (a 1.5-fold increase) in response to a protein-free diet. Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). These results show that the FoxO genes respond differently to nutritional and hormonal factors, suggesting a new mechanism for the regulation of FoxO-dependent gene expression by these factors. Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo.

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

scholarly journals DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα

2013 ◽  
Vol 451 (3) ◽  
pp. 453-461 ◽  
Author(s):  
Claudia C. S. Chini ◽  
Carlos Escande ◽  
Veronica Nin ◽  
Eduardo N. Chini
Keyword(s):  
Breast Cancer ◽  
Nuclear Receptor ◽  
Clock Genes ◽  
Mrna Levels ◽  
Protein Levels ◽  
The Stability ◽  
And Function ◽  
Interfering Rna ◽  
In Cells

The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbα controls circadian oscillations of several clock genes and Rev-erbα protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbα stability is essential for our understanding of these processes. In the present paper, we report that the protein DBC1 (Deleted in Breast Cancer 1) is a novel regulator of Rev-erbα. Rev-erbα and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbα repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Rev-erbα protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbα protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbα protein levels and function by DBC1 depends on both the N-terminal and C-terminal domains of DBC1. More importantly, in cells depleted of DBC1, there was a dramatic decrease in circadian oscillations of both Rev-erbα and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1.

Studies of renal injury. I. Gentamicin toxicity and expression of basolateral transporters

1996 ◽  
Vol 270 (2) ◽  
pp. F245-F253 ◽  
Author(s):  
J. H. Dominguez ◽  
C. C. Hale ◽  
M. Qulali
Keyword(s):  
Stress Response ◽  
Glucose Transporter ◽  
Mrna Level ◽  
Specific Protein ◽  
Renal Tubules ◽  
Mrna Levels ◽  
Glucose Transporter 1 ◽  
Protein Levels ◽  
Expression Of Genes ◽  
Glut1 Mrna

Gentamicin nephrotoxicity may arise in part from alterations in the expression of genes critical for renal proximal tubule metabolism. We tested the hypothesis that gentamicin suppressed the gene expression of the Na+/Ca2+ exchanger (NaCaX), glucose transporter 1 (GLUT1) and alpha 1-subunit of Na(+)-K(+)-ATPase (alpha 1-NKA) in renal tubules. The products of these genes mediate Na(+)-dependent Ca2+ efflux, glucose efflux and influx, and ATP-dependent Na+ efflux across tubular basolateral membranes, respectively. After 10 days of gentamicin intoxication (40 mg/kg ip, twice daily), levels of mRNAs encoding NaCaX and the cognate protein declined. GLUT1 mRNA levels increased, although GLUT1 protein levels were also reduced. Moreover, whereas alpha 1-NKA mRNA levels remained unchanged, alpha 1-NKA protein levels were also reduced. We suggest that the higher GLUT1 mRNA level is part of the stress response to tubular injury. However, regardless of the mRNA level, the most consistent effect of gentamicin was reduction of specific protein levels. We propose that failure to translate high levels of mRNA into proportionally high levels of protein, as in the case of GLUT1, may attenuate the expression of stress response gene products, and thus diminish the possibility of recovery in gentamicin intoxication.

scholarly journals Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma

2019 ◽  
Vol 20 (2) ◽  
pp. 375 ◽  
Author(s):  
Alexander W. Eckert ◽  
Susanne Horter ◽  
Daniel Bethmann ◽  
Johanna Kotrba ◽  
Tom Kaune ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Carbonic Anhydrase ◽  
Protein Level ◽  
Normal Tissue ◽  
Mrna Level ◽  
Mrna Levels ◽  
Cox's Regression ◽  
Carbonic Anhydrase 9

s: Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan–Meier and Cox’s regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox’s regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.

scholarly journals Differential Gene Expression of Steroid 5α-Reductase 2 in Core Needle Biopsies from Malignant and Benign Prostatic Tissue1

1997 ◽  
Vol 82 (7) ◽  
pp. 2210-2214
Author(s):  
Catarina Bjelfman ◽  
Torbjörn G. Söderström ◽  
Einar Brekkan ◽  
Bo Johan Norlén ◽  
Lars Egevad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Mrna Level ◽  
Transrectal Ultrasound ◽  
Mrna Levels ◽  
Prostate Hyperplasia ◽  
Noncancerous Tissue ◽  
Core Needle ◽  
Total Rna ◽  
Prostate Diseases

Androgens are implicated in the development of prostate cancer (CAP) and benign prostate hyperplasia. The conversion of testosterone to the more potent metabolite dihydrotestosterone by prostate-specific steroid 5α-reductase type 2 (5α-red2) is a key mechanism in the action of androgens in the prostate and is important in the promotion and progression of prostate diseases. Manipulation of the turnover of androgens is thus fundamental in the pharmacological treatment strategy. We have developed a sensitive solution hybridization method for quantification of the gene expression of 5α-red2 in core needle biopsies of the prostate. The 5α-red2-specific messenger RNA (mRNA) levels were measured in 50 human prostate transrectal ultrasound-guided core biopsies obtained from 31 outpatients (median age 72, range 57–88 yr) undergoing biopsy for diagnostic purposes. Significant differences were observed in the gene expression of 5α-red2 between cancerous and noncancerous tissue. In the 14 biopsies judged cancerous, the median 5α-red mRNA levels were 3.5 amol/ng total RNA compared with 12.0 amol/ng total RNA in the biopsies showing no cancer (P = 0.0018). The median 5α-red2 mRNA level in noncancerous tissue was thus 3.4 times higher than in the cancerous specimens.

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