Lymphocyte protein synthesis is increased with the progression of HIV-associated disease to AIDS

2001 ◽  
Vol 101 (6) ◽  
pp. 583-589 ◽  
Author(s):  
Giuseppe CASO ◽  
Peter J. GARLICK ◽  
Marie C. GELATO ◽  
Margaret A. MCNURLAN
Keyword(s):  
Protein Synthesis ◽  
Elevated Serum ◽  
Synthesis Rate ◽  
Hiv Positive ◽  
Lymphocyte Function ◽  
Healthy Controls ◽  
Aids Patients ◽  
Tnf Α

HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with l-[2H5]phenylalanine (45mg/kg body weight) in healthy volunteers (n = 7), in patients who were HIV-positive (n = 7) but asymptomatic, and in patients with AIDS (n = 8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9±1.28% and 9.1±0.53%/day respectively), but were significantly elevated in AIDS patients (14.0±1.16%/day; P < 0.05). The serum concentration of the cytokine tumour necrosis factor-α (TNF-α) increased with the progression of the disease, and TNF-α levels were significantly higher in AIDS patients (6.81±0.88ng/l) than in healthy controls (3.09±0.27ng/l; P < 0.05). Lymphocyte protein FSR was positively correlated with serum TNF-α concentration (r = 0.55, P = 0.009) and negatively correlated with CD4+ lymphocyte count (r =-0.70, P = 0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-α concentration in the late stages of HIV-associated disease.

Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation

1992 ◽  
Vol 262 (6) ◽  
pp. C1471-C1477 ◽  
Author(s):  
J. A. Chromiak ◽  
H. H. Vandenburgh
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Content ◽  
Total Protein ◽  
Weight Lifting ◽  
Mechanical Activity ◽  
Synthesis Rate ◽  
Protein Synthesis Rate

Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth.

scholarly journals Comparison of protein-synthesis rate of alveolar macrophages in vivo and in vitro

1984 ◽  
Vol 217 (3) ◽  
pp. 761-765 ◽  
Author(s):  
M H Oliver ◽  
P J Cole ◽  
G J Laurent
Keyword(s):  
Protein Synthesis ◽  
Alveolar Macrophages ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Novel Method

This paper describes and validates a novel method for measuring rates of protein synthesis of rabbit alveolar macrophages in vivo. A rate of 9.3%/day was obtained, compared with 48.9%/day measured in vitro. This study suggests that the procedures involved in the isolation of alveolar macrophages for study in vitro may themselves activate the cell.

scholarly journals Rates of protein turnover in vivo and in vitro in ventricular muscle of hearts from fed and starved rats

1984 ◽  
Vol 222 (2) ◽  
pp. 395-400 ◽  
Author(s):  
V R Preedy ◽  
D M Smith ◽  
N F Kearney ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Ventricular Muscle ◽  
Degradation Rates ◽  
Perfused Hearts

Starvation of 300 g rats for 3 days decreased ventricular-muscle total protein content and total RNA content by 15 and 22% respectively. Loss of body weight was about 15%. In glucose-perfused working rat hearts in vitro, 3 days of starvation inhibited rates of protein synthesis in ventricles by about 40-50% compared with fed controls. Although the RNA/protein ratio was decreased by about 10%, the major effect of starvation was to decrease the efficiency of protein synthesis (rate of protein synthesis relative to RNA). Insulin stimulated protein synthesis in ventricles of perfused hearts from fed rats by increasing the efficiency of protein synthesis. In vivo, protein-synthesis rates and efficiencies in ventricles from 3-day-starved rats were decreased by about 40% compared with fed controls. Protein-synthesis rates and efficiencies in ventricles from fed rats in vivo were similar to values in vitro when insulin was present in perfusates. In vivo, starvation increased the rate of protein degradation, but decreased it in the glucose-perfused heart in vitro. This contradiction can be rationalized when the effects of insulin are considered. Rates of protein degradation are similar in hearts of fed animals in vivo and in glucose/insulin-perfused hearts. Degradation rates are similar in hearts of starved animals in vivo and in hearts perfused with glucose alone. We conclude that the rates of protein turnover in the anterogradely perfused rat heart in vitro closely approximate to the rates in vivo in absolute terms, and that the effects of starvation in vivo are mirrored in vitro.

scholarly journals Inhibitory Effects of Urtica thunbergiana Ethanol Extract on Atopic Dermatitis-Induced NC/Nga Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 197
Author(s):  
Hien T.T. Ngo ◽  
Minzhe Fang ◽  
Eunson Hwang ◽  
Yoosung Kim ◽  
Bom Park ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Elevated Serum ◽  
Nuclear Factor ◽  
Hacat Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Urtica Thunbergiana

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that persists or repeatedly recurs in both childhood and adulthood. Urtica thunbergiana (UT) is an aroma herb with little-known pharmacological effects and anti-inflammatory activities against AD. This study investigated the immunomodulatory efficacy of 50% ethanol-extracted UT in necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ)-stimulated HaCaT cells in vitro and AD-Biostir-induced NC/Nga mice in vivo. The results showed that UT exhibits a dose-dependent increase in scavenged free radicals, reaching 76.0% ± 1.4% of scavenged 1,1-diphenyl-2-picrylhydrazyl at a concentration of 250 µg/mL. In addition, UT significantly downregulated the mRNA expression of the following pro-inflammatory cytokines and chemokines in TNF-α/IFN-γ-stimulated HaCaT cells: interleukin (IL)-6, IL-8, thymus- and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation normal T expressed and secreted. UT-treated HaCaT cells showed inhibition of the overexpression of chemokine-regulated signaling molecules, such as nuclear factor-kappa B, inhibitor of kappa B (IκBα), signal transducer and activator of transcription 1, and mitogen-activated protein kinases (MAPKs). UT dietary administration in AD-Biostir-induced NC/Nga mice treated and improved AD-like symptoms, such as scales, epidermal thickening, the dermatitis severity score, high trans-epidermal water loss, reduced skin hydration, increased mast cells, elevated serum immunoglobulin E levels, and an enlarged spleen. UT treatment inhibited the expression of phosphorylated forms of MAPKs, nuclear factor of activated T-cells 1, and regulator IκBα. It also upregulated filaggrin (FLG) production. Therefore, UT shows high anti-AD activity both in vitro and in vivo, and can be a useful anti-AD agent.

Determination of Protein Synthesis in Lymphocytes in Vivo after Surgery

1996 ◽  
Vol 91 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Pia Essén ◽  
Margaret A. McNurlan ◽  
Anders Thorell ◽  
Inga Tjäder ◽  
Giuseppe Caso ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Mixed Population ◽  
Synthesis Rate ◽  
Blood Lymphocytes ◽  
Mononuclear Leucocytes

1. The stimulation and depression of peripheral blood lymphocytes has previously been studied in vitro, showing an immune depression postoperatively; however, it is difficult to interpret these in vitro findings. Therefore, an in vivo technique has been established for determination of the fractional protein synthesis rate, as an index of metabolic activity in human peripheral blood lymphocytes, by using a stable isotope technique. 2. The rate of protein synthesis was calculated from the increase in enrichment of l-[2H5]phenylalanine in protein of a mixed population of mononuclear leucocytes, isolated by density gradient, after an intravenous flooding dose of l-[2H5]phenylalanine. A linear time course of isotopic incorporation into the cells was demonstrated. 3. The fractional rate of protein synthesis of a mixed population of mononuclear leucocytes was studied in relation to surgical interventions and to potential modifiers of the response. The fractional synthesis rate increased 24 h after open and laparoscopic cholecystectomy (49 ± 19% and 40 ± 14% respectively, P > 0.02), irrespective of postoperative total parenteral nutrition or preoperative glucose infusion. In contrast to surgery, insulin did not stimulate protein synthesis in peripheral mononuclear leucocytes.

scholarly journals Control by insulin and insulin-related growth factor 1 of protein synthesis in a cell-free translational system from chick-embryo fibroblasts

1987 ◽  
Vol 244 (1) ◽  
pp. 239-242 ◽  
Author(s):  
M W Pierce ◽  
K Coombs ◽  
M Young ◽  
J Avruch
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Chick Embryo ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Leucine Incorporation ◽  
A Cell ◽  
Embryo Fibroblasts

Insulin and insulin-related growth factor 1 (IGF-1) increase by 1.5-1.6-fold the rate of [3H]leucine incorporation into protein in primary monolayer cultures of chick-embryo fibroblasts (CEF); half-maximal hormone concentrations are 10 and 0.25 nM respectively. To investigate the mechanism of this effect, a rapid method is used to prepare a lysate from CEF which is active in protein synthesis. Lysate derived from cells treated for 30-150 min with insulin synthesized protein at 1.8-3.0-fold greater rate than did controls; the increased rate persisted for 20 min in vitro. Pactamycin (0.5 microM), an inhibitor of peptide-chain initiation, inhibited protein synthesis by 50% in lysates derived from insulin-treated and control cells. Thus insulin and IGF-1 cause an increase in the protein-synthesis rate in vivo, which persists in cell-free protein-synthesizing lysates of CEF.

scholarly journals Biochemical, Ameliorative and Cytotoxic Effects of Newly Synthesized Curcumin Microemulsions: Evidence from In Vitro and In Vivo Studies

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 817
Author(s):  
Abbas Rahdar ◽  
Mohammad Reza Hajinezhad ◽  
Saman Sargazi ◽  
Maryam Zaboli ◽  
Mahmood Barani ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Density Functional ◽  
Liver Enzymes ◽  
Elevated Serum ◽  
Ethyl Butyrate ◽  
Polymeric Chain ◽  
Prolonged Release ◽  
Advanced Therapies

Curcumin is known to exhibit antioxidant and tissue-healing properties and has recently attracted the attention of the biomedical community for potential use in advanced therapies. This work reports the formulation and characterization of oil-in-water F127 microemulsions to enhance the bioavailability of curcumin Microemulsions showed a high encapsulation efficiency and prolonged release. To investigate the interactions of curcumin with one unit of the polymeric chain of surfactant F127, ethyl butyrate, and sodium octanoate, as well as the interaction between ethyl butyrate and one unit of the F127 polymer chain, the Density Functional Theory (DFT) calculations at the M06-2X level of theory, were performed in water solution. The MTT assay was used to assess the cytotoxicity of free and encapsulated curcumin on non-malignant and malignant cell lines. Combination effects were calculated according to Chou-Talalay’s principles. Results of in vitro studies indicated that MCF7 and HepG2 cells were more sensitive to curcumin microemulsions. Moreover, a synergistic relationship was observed between curcumin microemulsions and cisplatin in all affected fractions of MCF7 and HepG2 cells (CI < 0.9). For in vivo investigation, thioacetamide-intoxicated rats received thioacetamide (100 mg/kg Sc) followed by curcumin microemulsions (30 mg/kg Ip). Thioacetamide-intoxicated rats showed elevated serum liver enzymes, blood urea nitrogen (BUN), and creatinine levels, and a significant reduction in liver superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). Curcumin microemulsions reduced liver enzymes and serum creatinine and increased the activity of antioxidant enzymes in thioacetamide-treated rats in comparison to the untreated thioacetamide-intoxicated group. Histopathological investigations confirmed the biochemical findings. Overall, the current results showed the desirable hepatoprotective, nephroprotective, and anti-cancer effects of curcumin microemulsions.

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

scholarly journals TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

2021 ◽  
Author(s):  
Hongli Zhou ◽  
Minyu Zhou ◽  
Yue Hu ◽  
Yanin Limpanon ◽  
Yubin Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Enrichment Analysis ◽  
Angiostrongylus Cantonensis ◽  
Gene Set Enrichment Analysis ◽  
Caspase 8 ◽  
Cns Injury ◽  
Vitro Assay ◽  
Tnf Α

AbstractAngiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

scholarly journals 5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

2021 ◽  
Vol 22 (3) ◽  
pp. 1083
Author(s):  
Sukkum Ngullie Chang ◽  
Se Ho Kim ◽  
Debasish Kumar Dey ◽  
Seon Min Park ◽  
Omaima Nasif ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Elevated Serum ◽  
In Vitro Study ◽  
Biological Properties ◽  
Autophagic Flux ◽  
Serum Aminotransferase ◽  
Ccl4 Treatment

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.

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