scholarly journals A comparative analysis of erythropoietin and carbamoylated erythropoietin-induced proteome profiles

2020 ◽  
Author(s):  
Neeraj Kumar Tiwari ◽  
Monica Sathyanesan ◽  
Vikas Kumar ◽  
Samuel S Newton

Abstract In recent years erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity and produce adverse effects in non-anemic populations. Carbamyolated erythropoietin (CEPO), a chemically engineered modification of EPO, is non-erythropoietic but retains the neurotrophic and neurotrophic activity of EPO. Blood profile analysis after EPO and CEPO administration showed that CEPO has no effect on red blood cell or platelet counts. We conducted an unbiased, quantitative, mass spectrometry-based proteomics study to comparatively investigate EPO and CEPO-induced protein profiles in neuronal phenotype PC12 cells. Bioinformatics enrichment analysis of the protein expression profiles revealed the upregulation of protein functions related to memory formation such as synaptic plasticity, long term potentiation (LTP), neurotransmitter transport, synaptic vesicle priming, and dendritic spine development. The regulated proteins, with roles in LTP and synaptic plasticity, include Neudesin, Chromogranin b, Cortactin, Elongation initiation factor 3a and Proteasome 26s subunit, ATPase. We examined the expression of a subset of regulated proteins by immunohistochemical analysis in mouse brain. The results of our study sheds light on potential mechanisms whereby EPO and CEPO produce cognitive enhancing effects in clinical and preclinical studies.

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 359
Author(s):  
Neeraj K. Tiwari ◽  
Monica Sathyanesan ◽  
Vikas Kumar ◽  
Samuel S. Newton

In recent years, erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive-enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity and produce adverse effects in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered modification of EPO, is non-erythropoietic but retains the neurotrophic and neurotrophic activity of EPO. Blood profile analysis after EPO and CEPO administration showed that CEPO has no effect on red blood cell or platelet counts. We conducted an unbiased, quantitative, mass spectrometry-based proteomics study to comparatively investigate EPO and CEPO-induced protein profiles in neuronal phenotype PC12 cells. Bioinformatics enrichment analysis of the protein expression profiles revealed the upregulation of protein functions related to memory formation such as synaptic plasticity, long term potentiation (LTP), neurotransmitter transport, synaptic vesicle priming, and dendritic spine development. The regulated proteins, with roles in LTP and synaptic plasticity, include calcium/calmodulin-dependent protein kinase type 1 (Camk1), Synaptosomal-Associated Protein, 25 kDa (SNAP-25), Sectretogranin-1 (Chgb), Cortactin (Cttn), Elongation initiation factor 3a (Eif3a) and 60S acidic ribosomal protein P2 (Rplp2). We examined the expression of a subset of regulated proteins, Cortactin, Grb2 and Pleiotrophin, by immunofluorescence analysis in the rat brain. Grb2 was increased in the dentate gyrus by EPO and CEPO. Cortactin was induced by CEPO in the molecular layer, and pleiotrophin was increased in the vasculature by EPO. The results of our study shed light on potential mechanisms whereby EPO and CEPO produce cognitive-enhancing effects in clinical and preclinical studies.


Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 414
Author(s):  
Gal Avishai ◽  
Idan Rabinovich ◽  
Hanna Gilat ◽  
Gavriel Chaushu ◽  
Liat Chaushu

Sialolithiasis is a chronic disease in which a sialolith (salivary stone) causes recurrent inflammation of the affected salivary gland. Anemia of inflammation is a well-described pathology in which a chronic inflammatory disease leads to a reduction in the red blood cell count, hemoglobin and hematocrit values. In this retrospective cohort study, we aim to find whether removal of the sialolith and alleviation of the inflammation affect the complete blood count results. We examined data regarding forty-nine patients who underwent surgery for the removal of a submandibular gland sialolith using the duct-stretching technique. Complete blood counts two years before and after the surgical procedure were collected. The average pre-procedure and post-procedure values were calculated for each patient to establish the average blood profile. The pre- and post-procedure values were compared to evaluate the effect of the surgical treatment on the blood profile. We found that the average blood count values for patients with sialolithiasis were towards the lower end of the normal range. Post-surgery, a significant increase in hematocrit, hemoglobin and red blood cell count was observed, which was more pronounced in the older age group and in patients with co-morbidities. We conclude that sialolith removal surgery is associated with significant improvement in the complete blood count values, especially in the elderly and in patients and with co-morbidities. The speculated pathogenesis is relative anemia of inflammation.


1976 ◽  
Vol 13 (4) ◽  
pp. 207-214
Author(s):  
Hiroshi Yamanouchi ◽  
Hideo Tohgi ◽  
Masakuni Kameyama ◽  
Mototaka Murakami ◽  
Tamotsu Matsuda

2013 ◽  
Vol 40 (6) ◽  
pp. 903-909 ◽  
Author(s):  
Jolanta Parada-Turska ◽  
Wojciech Zgrajka ◽  
Maria Majdan

Objective.Previously we demonstrated that kynurenic acid (KYNA), an endogenous metabolite of kynurenine, is present in the synovial fluid of patients with rheumatoid arthritis (RA). KYNA inhibits proliferation of synoviocytesin vitro. The goal of our study was to compare KYNA concentrations in synovial fluid and blood of patients with RA, inflammatory spondyloarthropathies (SpA), and osteoarthritis (OA).Methods.Serum and synovial fluid samples were obtained from 189 patients with RA, 56 patients with SpA, and 32 patients with OA. KYNA was separated using a high-performance liquid chromatography system and measured fluorometrically.Results.KYNA concentration in synovial fluid obtained from patients with RA and SpA was significantly lower than that in patients with OA (p < 0.05). The concentration of KYNA in serum of patients with RA, SpA, and OA did not differ among all groups studied. The positive correlation between KYNA content in synovial fluid and serum was found in patients with RA (p < 0.05). Univariate linear regression analysis demonstrated that fibrinogen was significantly associated with KYNA in synovial fluid (p < 0.05), and red blood cell counts, morning stiffness, and pain scores were significantly associated with KYNA level in serum (all p < 0.05). Multivariate regression analysis revealed correlation between the following independent variables: hemoglobin level, hematocrit, red blood cell count in conjunction with age and KYNA content in synovial fluid. A lack of correlation was observed between KYNA content in synovial fluid of patients with RA and other clinical and laboratory measures of disease activity.Conclusion.Our data show a local deficit of KYNA in inflammatory states.


2015 ◽  
Vol 36 (5) ◽  
pp. 3227
Author(s):  
Paulo Henrique da Silva ◽  
Cecília Braga Laposy ◽  
Rogério Giuffrida ◽  
Marina Platzeck Chaves ◽  
Maickon Willian de Freitas

<p>Erythrocyte alterations require making decisions, guiding clinical conduct, determining prognoses, and choosing therapy options for diseases. Automated devices that can perform blood cell counts allow for calculation of amplitude distribution of erythrocytes red blood cell distribution width (RDW) and its fractions (RDW-CV and RDW-SD). It also evaluates quantitatively the heterogeneity of each erythrocyte, especially in the feline species where presence of anisocytosis is common, even under normal conditions. Contrary to human medicine where there has been universal acceptance of RDW, there are only a handful of veterinarians and laboratories that currently use this parameter as a diagnostic tool for differential laboratory diagnosis of anemia in veterinary medicine, possibly owing to unfamiliarity with the application. Faced with limited availability of information in scientific literature regarding RDW values for the domestic cat, this study aimed to associate RDW values with erythrocytes, hematocrit, hemoglobin, and mean corpuscular volume (MCV) in 407 adult cats of no defined pedigree (n = 218 males and n = 189 females; 335 non-anemic and 72 anemic). In the present study, RDW-SD values in anemic cats were 20.4% above those considered normal, while RDW-CV values were 25.2% higher than those considered normal for the species. We concluded that interpretation of RDW values is an important tool for evaluating heterogeneity of erythrocytes with regard to anemia. Even in non-anemic animals, increased levels of RDW may suggest early erythrocyte alterations.</p>


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Julia Greco ◽  
Allison Sloan ◽  
Christa Palancia Esposito ◽  
Aaron Van Dyke ◽  
Catherine Andersen

Abstract Objectives Serum lipids may influence the lifespan of erythrocytes, and have been associated with clinical erythrocyte indices at the population level. Consumption of whole eggs vs. egg whites exerts varying effects on serum lipids and lipoprotein profiles; therefore, we investigated whether egg-induced changes in serum lipids correspond to changes in clinical erythrocyte markers. Methods Young, healthy men and women (18–35y, BMI < 30 kg/m2, n = 11) were recruited to participate in an ongoing intervention trial. All subjects followed an egg-free diet for 4 weeks, then were randomized to consume either 3 whole eggs or 3 egg whites per day for 4 weeks. Fasting serum lipids, complete blood cell counts, and dietary intake analysis was performed at the end of each study period. Results Average serum lipids and erythrocyte indices were within normal ranges at the end of each diet period. Changes in total cholesterol following the whole egg (+4.8%) and egg white (0.4%) diet period were not significant as compared to the egg-free diet period. Similarly, clinical erythrocyte markers were not significantly altered by daily consumption of whole eggs or egg whites. However, changes in total cholesterol and LDL-cholesterol between diet periods were positively correlated with changes in total red blood cell counts and hemoglobin. Total cholesterol was additionally correlated with hematocrit levels, and negatively associated with red cell distribution width. Total red blood cell counts and hemoglobin were further correlated with changes in the total cholesterol to HDL-cholesterol ratios, but not HDL-cholesterol alone. Conclusions Our findings indicate that egg-induced changes in serum lipids are associated with clinical erythrocyte indices, and that total cholesterol levels and dyslipidemia may be more significant determinants of erythrocyte profiles. Funding Sources This study was funded by an Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture.


1983 ◽  
Vol 61 (4) ◽  
pp. 930-933 ◽  
Author(s):  
Deborah A. Duffield ◽  
Sam H. Ridgway ◽  
Lanny H. Cornell

Bottlenose dolphins, Tursiops truncatus, can be separated into coastal and offshore ecotypes based upon hemoglobin levels, packed cell volumes, and red blood cell counts, the offshore form having higher values for all three measures. Captive-bred crosses between coastal and offshore types produce animals with intermediate hematologic profiles suggesting a significant genetic basis for these differences.


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