Erythrocytes activation

The mechanism by which the plasma membrane electron transport activates the exchanger is not established. Since the electron transport system in erythrocytes activates tyrosine phosphorylation, specifically on band three protein (Harrison et al., 1991), and the exchanger can be activated by phosphorylation through tyrosine kinase coupled to MAP kinases, which ultimately phosphorylate serine on the exchanger, it is likely that the activation of the exchanger by the electron transport system is based on activation of protein tyrosine kinase (Sardet et al., 1991). 

Acetylcholine perchlorate was used as the substrate for erythrocyte and brain cholinesterase. The washed erythrocytes from 2 ml. of blood were diluted with the solution mentioned above, to which saponin was added to lake the cells, and an aliquot was taken for assay. The results are expressed as micromoles of acetic acid produced per minute per milliliter of whole blood. Because we preferred to express erythrocyte activity in terms of whole blood, we adjusted each final value to its equivalent at a hematocrit of 50%. This calculation, involving the hematocrit obtained on each blood sample, serves to differentiate enzyme inhibition from the variability in activity associated with abnormal plasma-erythrocyte volume ratios. 

Neat VX, 20 ig kg-1, was applied to the skin of four subjects, while four other subjects received 20 p.g kg-1 mixed 1 1 with octylamine, and four others received neat VX, 35 pg kg-1 (Lubash and Clark, 1960). Seven were symptomatic with insomnia, nightmares, lightheadedness, nausea, epigastric discomfort, vomiting and diarrhea. (The whole blood activity was 14-38% of control in these subjects.) The whole blood erythrocyte activity was above 42% of control activity in the five asymptomatic subjects. Plasma and urinary electrolytes, BSP excretion, SGOT, SGPT and serum amylase were all normal following exposure. 

Nilsson, A., Engberg, G., Henneberg, S., Danielson, K., and De Verdier, C.-H. (1990). Inverse relationship between age-dependent erythrocyte activity of methaemoglobin reductase and prilocaine-induced methaemoglobinaemia during infancy. Br. J. Anaesth. 64,72-76. 

No evidence for the presence of a known enzyme abnormality causing purine overproduction could be obtained. The erythrocyte activity of hypoxanthine-guanine phos-phoribosyltransferase (HGPRT), of adenine phosphoribosyltransferase (APRT), and of phosphoribosylpyrophosphate (PRPP) synthetase were all in the normal range. Erythrocyte PRPP generation, as well as the acitivity of the pentose phosphate pathway was also normal (Table 1). In addition, the rate of de novo synthesis of purine nucleotides in cultured skin fibroblasts from the patient was found to be normi. 

Mallard ducks Lead pellet ingestion, PbB at 4 weeks, 100 g dl Pb level and 8-ALA-D activity in blood and brain regions Cerebellar 8-ALA-D activity reduced 50% at Pb<0.5 ppm erythrocyte activity reduced 75% liver activity reduced 50% at Pb 2.5 ppm Dieter and Finley (1979)... 

These results suggest that renin is an enzyme-like substance which is activated by a kinase-like material contained in the protein fraction of plasma and whole blood. And later they (107) wrote These experiments. .. therefore suggest that either whole blood, plasma, or filtrate of laked erythrocytes activates the vasoconstrictor action of renin, or that a latent vasoconstrictor substance in blood is activated by renin. ... 

In humans, thiamine is both actively and passively absorbed to a limited level in the intestines, is transported as the free vitamin, is then taken up in actively metabolizing tissues, and is converted to the phosphate esters via ubiquitous thiamine kinases. During thiamine deficiency all tissues stores are readily mobilhed. Because depletion of thiamine levels in erythrocytes parallels that of other tissues, erythrocyte thiamine levels ate used to quantitate severity of the deficiency. As deficiency progresses, thiamine becomes indetectable in the urine, the primary excretory route for this vitamin and its metaboHtes. Six major metaboHtes, of more than 20 total, have been characterized from human urine, including thiamine fragments (7,8), and the corresponding carboxyHc acids (1,37,38). 

Proteins that can flip phospholipids from one side of a bilayer to the other have also been identified in several tissues (Figure 9.11). Called flippases, these proteins reduce the half-time for phospholipid movement across a membrane from 10 days or more to a few minutes or less. Some of these systems may operate passively, with no required input of energy, but passive transport alone cannot establish or maintain asymmetric transverse lipid distributions. However, rapid phospholipid movement from one monolayer to the other occurs in an ATP-dependent manner in erythrocytes. Energy-dependent lipid flippase activity may be responsible for the creation and maintenance of transverse lipid asymmetries. 

The gradients of H, Na, and other cations and anions established by ATPases and other energy sources can be used for secondary active transport of various substrates. The best-understood systems use Na or gradients to transport amino acids and sugars in certain cells. Many of these systems operate as symports, with the ion and the transported amino acid or sugar moving in the same direction (that is, into the cell). In antiport processes, the ion and the other transported species move in opposite directions. (For example, the anion transporter of erythrocytes is an antiport.) Proton symport proteins are used by E. coU and other bacteria to accumulate lactose, arabinose, ribose, and a variety of amino acids. E. coli also possesses Na -symport systems for melibiose as well as for glutamate and other amino acids. 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

Obsessive-compulsive disorders Erythrocytes from patients with obsessive-compulsive disorder have significantly higher calpain activities than normal controls which could not be attributed to differences in memory function46... 

Clinical studies, available only for entacapone and tolcapone, support preclinical findings. A dose-dependent (100-800 mg) inhibition of the COMT activity of the erythrocytes can be seen after nitrocatechols. However, effective and sufficient dose levels of both entacapone and tolcapone, given concomitantly with L-dopa and DDC inhibitors to patients with Parkinson s disease, appear to be 100-200 mg. However, the treatment strategies of entacapone and tolcapone differ entacapone is a short-acting compound that is given with each dose of L-dopa, and COMT activity may even... 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Water soluble protein with a relative molecular mass of ca. 32600, which particularly contains copper and zinc bound like chelate (ca. 4 gram atoms) and has superoxide-dismutase-activity. It is isolated from bovine liver or from hemolyzed, plasma free erythrocytes obtained from bovine blood. Purification by manyfold fractionated precipitation and solvolyse methods and definitive separation of the residual foreign proteins by denaturizing heating of the orgotein concentrate in buffer solution to ca. 65-70 C and gel filtration and/or dialysis. 

M (decreased plasma 67-88%, erythrocyte 9-20%, and brain 76-79% cholinesterase activity)... 

When methyl parathion was given orally to rats at doses of 1.5 mg/kg and to guinea pigs at 50 mg/kg, plasma, erythrocyte, and brain cholinesterase activity was maximally inhibited within 30 minutes after administration. In rodents of both species that died after acute intoxication, brain cholinesterase levels decreased to 20% of control values and often to 5-7% (Miyamoto et al. 1963b). The species difference in susceptibility to orally administered methyl parathion is noted in Section 3.2.2.1. 

A dose-response relationship was noted in dogs exposed to 0.03, 0.3, or 3.0 mg/kg/day methyl parathion in the diet for 13 weeks (Daly 1989). Significant reductions in erythrocyte cholinesterase activity (20-23%) and cholinesterase activity in the pons and cerebellum of the brain (43-54%) occurred in dogs... 

The only other information regarding the potential for age-related differences in susceptibility to methyl parathion came from a study by Garcia-Lopez and Monteoliva (1988). The investigators showed increasing mean erythrocyte acetylcholinesterase activity levels with increasing age range, starting at birth (in 10-year increments and >60 years of age) in both males and females. However, it is not known whether increased erythrocyte acetylcholinesterase activity indicates a decreased susceptibility to methyl parathion toxicity. 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

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