Erythrocyte caspase-3 levels in children with chronic kidney disease

Polak−Jonkisz, Dorota; Purzyc, Leszek; Szcepańska, M.; Makulska, Irena

doi:10.1016/j.clinbiochem.2012.10.021

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…The sufficiently high ATP concentration is decisive for the energetic level of RBC, being simultaneously, a substrate for PMCA and PKC, controlling the effects of their activity. In our opinion, the cell protects itself against ATP deficit by enhancing glycolytic flux in result of the direct attack on band-3 [4]. It results in increased phosphorylation of band-3 protein.…”

Section: Dear Editormentioning

confidence: 87%

“…Phorbol ester (PMA -phorbol-12-myristate-13-acetate) activates protein kinases C (PKC) and these kinases phosphorylate a number of cytoskeletal and cytoplasmic proteins, e.g. : cell injury, proliferation or eryptosis [2,4] (Fig. PMA stimulates the production of reactive oxygen species (ROS) by plasma membrane NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activation.…”

Section: Dear Editormentioning

confidence: 99%

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The PMA action via metabolism of uremic erythrocytes

Polak−Jonkisz

Zwołińska

Purzyc

2015

Clinical Hemorheology and Microcirculation

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Dear Editor,In the recent article Carelli-Alinovi C et al. [1] are raising an important issue of the link, established between PKC and caspase 3 activities and its association with NO metabolism. The authors made a normal, mature red blood cell (RBC) the object of their observations and analysis. Phorbol ester (PMA -phorbol-12-myristate-13-acetate) activates protein kinases C (PKC) and these kinases phosphorylate a number of cytoskeletal and cytoplasmic proteins, e.g. band-3 or endothelial NO synthase (eNOS), localised in the cytoplasmic membrane of RBC [3]. PMA stimulates the production of reactive oxygen species (ROS) by plasma membrane NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activation. These processes play a significant role in maintaining the mechanical and morphological properties of the RBC membrane. In our ex vivo studies of uremic erythrocytes, we also found PKC activation, which could have been released either during erythrocyte maturation or under the influence of biochemical factors, e.g., uremic toxins or oxidative or mechanical stress [unpublished data]. In line with the authors, we found a certain drop in the activity of eNOS, that may have resulted from calmodulin effects, which we used to observe in the course of chronic kidney disease and not merely from phosphorylation of the Ca 2+ -binding domain. In their manuscript, the authors seek to explain the role of PKC in the activation of caspases [1]. These proteases are involved in the degradation process of membrane proteins, among others, band-3, modulating its biological functions. Caspase-3 may be induced either directly or indirectly via a series of events between caspase-3 and PKC. Thus, perhaps, it is PMA which, whilst inducing oxidative stress, activates caspase-3, although the mechanism is not very clear. The authors are trying to explain the PMA−→PKC−→caspases−→cellular membrane sequence, but they do not take into account the role of free, cytoplasmic calcium (Ca 2+ i ), the concentration of which in physiological RBCs is many times lower than outside of erythrocytes. It may then be treated as an intracellular "signalling" molecule, the

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Section: Dear Editormentioning

confidence: 87%

Section: Dear Editormentioning

confidence: 99%

The PMA action via metabolism of uremic erythrocytes

Polak−Jonkisz

Zwołińska

Purzyc

2015

Clinical Hemorheology and Microcirculation

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“…The level of cytoplasmic ATP e and the “energy charge” values of erythrocytes are determined not only by the rate of synthesis in the process of anaerobic glycolysis and the process of reutilization of adenyl nucleotides. In our 2012 study also conducted on CKD children, we observed a gradual increase in ATP e concentration from stage I-III CKD [ 26 ]. In the pre-dialysis stage, however, there was a large decrease in the concentration of erythrocytic ATP e .…”

Section: Discussionmentioning

confidence: 99%

“…In the pre-dialysis period, however, there was a significant decrease in LDH activity in relation to the examined patients and in relation to the control group. The accompanying CKD hypoxia is also of importance; greater transport of lactates and ion H + ions inside the cell as a result of, among others, inactivation of LDH [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Adenine Nucleotide Metabolites in Uremic Erythrocytes as Metabolic Markers of Chronic Kidney Disease in Children

Piechowicz

Gamian

Zwołińska

et al. 2021

JCM

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Chronic kidney disease (CKD) is associated with multifaceted pathophysiological lesions including metabolic pathways in red blood cells (RBC). The aim of the study was to determine the concentration of adenine nucleotide metabolites, i.e., nicotinamide adenine dinucleotide (NAD)-oxidized form, nicotinamide adenine dinucleotide hydrate (NADH)-reduced form, nicotinic acid mononucleotide (NAMN), β-nicotinamide mononucleotide (NMN), nicotinic acid adenine dinucleotide (NAAD), nicotinic acid (NA) and nicotinamide (NAM) in RBC and to determine a relationship between NAD metabolites and CKD progression. Forty-eight CKD children and 33 age-matched controls were examined. Patients were divided into groups depending on the CKD stages (Group II-stage II, Group III- stage III, Group IV- stage IV and Group RRT children on dialysis). To determine the above-mentioned metabolites concentrations in RBC liquid chromatography-mass spectrometry was used. Results: the only difference between the groups was shown concerning NAD in RBC, although the values did not differ significantly from controls. The lowest NAD values were found in Group II (188.6 ± 124.49 nmol/mL, the highest in group IV (324.94 ± 63.06 nmol/mL. Between Groups II and IV, as well as III and IV, the differences were statistically significant (p < 0.032, p < 0.046 respectively). Conclusions. CKD children do not have evident abnormalities of RBC metabolism with respect to adenine nucleotide metabolites. The significant differences in erythrocyte NAD concentrations between CKD stages may suggest the activation of adaptive defense mechanisms aimed at erythrocyte metabolic stabilization. It seems that the implementation of RRT has a positive impact on RBC NAD metabolism, but further research performed on a larger population is needed to confirm it.

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“…We currently show for the first time that the percentage of irreversibly modified RBCs is a function of baseline Hb concentration, highlighting the close relationship between severe RBC shape distortions, inflammation, and anemia in ESRD. Uremic toxins may induce PS exposure on RBCs, accelerating therefore their clearance and pathophysiological interactions with immune cells, platelets, and endothelium, through molecular pathways involving or not Ca 2+ influx, as highlighted by the segregation pattern of those variables following a factor analysis as well.…”

Section: Discussionmentioning

confidence: 99%