PubMed Health⌕ Search

Biomedical subjects

T H Thomas

Publications and source records attributed to T H Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Inflammation in cardiovascular disease and regulation of the actin cytoskeleton in inflammatory cells: the actin cytoskeleton as a target.

Cardiovascular disease is prevalent in developed countries causing very large burdens to health services. The underlying pathology is atheromatous plaque in the sub-endothelial region of the vascular wall. High levels of low density lipoprotein cholesterol and high blood pressure cause endothelial damage. Atheroma develop from a response to this injury that is perpetuated to chronic inflammation. The invasion of inflammatory leukocytes into atheroma during its development and in the precipitation of acute thrombotic events is mediated by adhesion molecules on the cell surface. These are regulated by the actin filament cytoskeleton which also mediates intracellular signalling from them. The actin cytoskeleton is central to NADPH oxidase activation that produces superoxide which is an intracellular signalling molecule for the hypertensive and inflammatory actions of angiotensin II. There are polymorphisms in actin filament proteins such as adducin and caldesmon and in the promoter regions of tropomyosins that may cause individual variation in these processes. Many signalling molecules in the actin filament response to inflammatory stimuli and in signalling downstream from actin filaments are small G-proteins that require post-transcriptional modification by isoprenoids from the cholesterol synthetic pathway. Statins deplete the isoprenoids and so down regulate G-proteins that mediate the inflammatory response. Angiotensin converting enzyme inhibitors and angiotensin II receptor type 1 antagonists decrease angiotensin II stimulated superoxide production thus decreasing not only blood pressure but also inflammation. The anti-inflammatory effects of these drugs, involving altered actin filament function, are a major contributor to their benefits in the treatment of cardiovascular disease. The feasibility of modifying the behaviour of actin filament proteins as a therapeutic approach for cardiovascular disease is considered.

Actins↗
PubMed2004

Impaired neutrophil store-mediated calcium entry in Type 2 diabetes.

BACKGROUND: In Type 2 diabetes impaired neutrophil function leads to increased bacterial infection and cardiovascular disease. Many neutrophil functions depend on calcium signalling, which involves release of calcium from intracellular stores and subsequently translocation of stores via the cytoskeleton to the plasma membrane, causing store-mediated calcium entry (SMCE) into the cell. We hypothesized that in Type 2 diabetes there would be a defect in SMCE. MATERIALS AND METHODS: Neutrophils were prepared from patients with Type 2 diabetes (DM, n=15) and controls (NC, n=15). Free cytosolic calcium [Ca2+]i was measured with Fura-2 in resting cells and after stimulation of calcium release with fMLP and thapsigargin. RESULTS: Baseline [Ca2+]i was higher in neutrophils from the patients than the controls (NC 65 +/- 5 nm, DM 80 +/- 4 nm, P<0.05). However, after fMLP-treatment [Ca2+]i was significantly lower in the patients (NC 301 +/- 28 nm, DM 210 +/- 20 nm, P<0.01). The greater increase in controls was not observed when cells were treated with fMLP in the absence of extracellular calcium (-fold increase NC 2.9 +/- 0.5, DM 2.7 +/- 0.3). Treatment of cells with thapsigargin caused a similar greater increase in [Ca2+]i in the controls than in the patients that was not seen in the absence of extracellular calcium (-fold increase with Ca2+ NC 5.2 +/- 1.0, DM 3.0 +/- 0.4, P<0.05; fold increase without Ca2+ NC 2.5 +/- 0.4, DM 2.2 +/- 0.2). CONCLUSIONS: In Type 2 diabetes there is a defect in neutrophil calcium signalling which results in a lesser increase in free cytosolic calcium owing to impaired influx across the plasma membrane. Abnormal calcium signalling is likely to be important in the pathogenesis of diabetic complications.

Calcium↗
PubMed2004

Increasing neutrophil F-actin corrects CD11b exposure in Type 2 diabetes.

BACKGROUND: Leukocyte dysfunction contributes to the pathogenesis of diabetic vascular complications. Neutrophils adhere to the endothelium through the beta(2)integrin CD11b/CD18. In Type 2 diabetes, neutrophil surface CD11b expression is increased and is associated with impaired actin polymerization. This study aimed to determine whether increasing neutrophil actin polymerization could correct the defect in CD11b exposure. DESIGN: Neutrophil actin polymerization was stimulated with the tyrosine phosphatase inhibitor phenylarsine oxide (PAO), and cytoskeletal phosphotyrosine was monitored by immunoblotting Triton X-100 insoluble fractions of cells. Neutrophil F-actin was measured with phalloidin-FITC staining, and surface CD11b expression was determined with anti-CD11b-PE before analysis with flow cytometry. RESULTS: Phenylarsine oxide caused an increase in phosphotyrosine in neutrophils from both patients with Type 2 diabetes (DM) and controls (NC) (-fold increase: NC, 1.43 +/- 0.16; DM, 1.46 +/- 0.10). The response to PAO in terms of phalloidin-binding was impaired in neutrophils from patients [phalloidin-FITC MFI area under the curve, NC 200 +/- 5 (x 10(3)), DM 124 +/- 9 (x 10(3)), P < 0.0001]. Phenylarsine oxide at concentrations < 10 micro mol L(-1) also caused loss of CD11b from neutrophil surfaces that was impaired in samples from patients [CD11b sites area under the curve NC 90 +/- 6 (x 10(3)), DM 121 +/- 9 (x 10(3)), P < 0.002]. However, in neutrophils from patients, incubation with PAO at a concentration of > 10 micro mol L(-1) caused a significant increase in intracellular F-actin and CD11b down-regulation equivalent to that observed in controls. CONCLUSION: In Type 2 diabetes, impaired neutrophil actin polymerization even in response to increasing cytoskeletal phophotyrosine suggests a downstream defect. Furthermore, increasing actin polymerization, above a minimum threshold level, corrects the defect in integrin exposure. Correction of the actin polymerization defect in Type 2 diabetes could improve the prognosis of diabetic vascular complications.

Actins↗
PubMed2002

Impaired neutrophil actin assembly causes persistent CD11b expression and reduced primary granule exocytosis in Type II diabetes.

AIMS/HYPOTHESIS: Neutrophil dysfunction has a role in the pathogenesis of complications in Type II (non-insulin-dependent) diabetes mellitus. Neutrophils adhere through expression of the beta(2)integrin CD11b/CD18 which closely associates with the actin cytoskeleton. The aim of this study was to investigate the effect of actin polymerisation on CD11b expression and exocytosis of the primary granule marker CD69 in neutrophils from patients with Type II diabetes. METHODS: Neutrophils were activated with fMLP or PMA, actin polymerisation was inhibited with cytochalasin D. Cells were stained for CD11b and CD69 expression and intracellular F-actin was measured with phalloidin-FITC. Cellular fluorescence was measured by flow cytometry. Actin content of Triton X-100 fractions of cells was measured by SDS-PAGE and Coomassie blue staining. RESULTS: PMA caused an increase in neutrophil F-actin that was greater in control subjects than in patients with Type II diabetes (50.8% vs 33.4%, p<0.001) and correlated with actin integrated optical density (IOD) by SDS-PAGE ( r=0.74, p=0.01). Loss of CD11b from cell surfaces only occurred in neutrophils with high F-actin. The proportion of cells losing CD11b was lower in patients than in control subjects (23.1% vs 37.5%, p<0.001) and lowest in patients with additional cardiovascular risk markers (20.1% vs 27.7%; p<0.05). Cytochalasin D prevented loss of CD11b ( p<0.001). CD69 expression was reduced in patients with Type II diabetes (22.6% vs 36.4%, p<0.001) and correlated with F-actin content ( r=0.78, p<0.0001). CONCLUSION/INTERPRETATION: In Type II diabetes impaired neutrophil actin polymerisation leads to persistent expression of CD11b and reduced exocytosis of primary granules and could contribute to the pathogenesis of diabetic complications.

Actins↗
PubMed2001

Rapid fusion of granules with neutrophil cell membranes in hypertensive patients may increase vascular damage.

In essential hypertension (EHT) the presence of a metabolic syndrome increases the risk of cardiovascular disease. A cell membrane abnormality is implicated but its role in cardiovascular disease is unclear. Neutrophil accumulation, which occurs by beta2-integrin (CD11b/CD18) expression, followed by release of proinflammatory factors from primary vesicles is an important factor in vascular damage. CD11b and CD69 expression on neutrophils from normal controls and EHT patients was determined by fluorescence-activated cell scanning. Neutrophils were activated with phorbol myristate acetate (PMA). Protein kinase C (PKC) and calpain were inhibited with bisindolylmaleimide and E64d, respectively. In EHT patients CD11b was not increased on neutrophils at rest. However, EHT neutrophils more readily expressed CD11b on incubation in phosphate-buffered saline and more cells went on to exocytose primary granules indicated by expression of CD69. Stimulation with PMA caused more rapid activation in EHT neutrophils with expression of CD11b, followed rapidly by exocytosis of primary granules. Bisindolylmaleimide slowed but did not prevent CD11b expression, which, together with primary granule exocytosis, continued to be faster in EHT neutrophils. E64d also slowed but did not prevent either CD11b expression or primary granule exocytosis, but this inhibitor did abolish the difference between NC and EHT neutrophils. The membrane abnormality in EHT may contribute to cardiovascular risk by increasing the rate of vesicle fusion with the cell membrane to increase neutrophil accumulation and release of inflammatory agents at sites of vascular damage. Calpain activation may be the rate-limiting component that is abnormal.

Adult↗
PubMed2001

Abnormal thiol reactivity of tropomyosin in essential hypertension and its association with abnormal sodium-lithium countertransport kinetics.

OBJECTIVES: To identify a thiol protein that is abnormal in a subgroup of essential hypertensive (EHT) patients who have a strong family history of hypertension and cardiovascular disease and have a low Km of erythrocyte Na/Li countertransport (CT). METHODS: To detect biotin maleimide labelling of a key thiol protein to investigate its reaction with N-ethylmaleimide (NEM) in normal and EHT erythrocytes. RESULTS: The thiol protein of 33 kDa apparent molecular weight (p33) identified by the loss of labelling with biotin maleimide was identified as tropomyosin due to its retarded running in 6 mol/l urea gels and immunoblotting. The NEM reaction with p33 detected by loss of subsequent biotin maleimide labelling is biphasic in normal control erythrocytes with the rate in the first 30 s double that after 30 s. In EHT erythrocytes NEM reaction (1) after 30 s is faster than normal and (2) in the first 30 s causes a paradoxical increase in apparent biotin maleimide labelling. In normal control erythrocytes, the loss of biotin maleimide labelling with NEM reaction or the faster phenylmaleimide reaction follows the same time course as the decrease in Km of Na/Li CT. CONCLUSIONS: NEM reaction with p33 requires two thiols. Only the cytoskeletal form of tropomyosin from the TM3 gene has more than one thiol group and agrees with SDS-PAGE mobility. Tropomyosin is a strong candidate to explain the familial abnormality in EHT with abnormal Na/ Li CT and it could explain many of the characteristics of this disease.

Biotin↗
PubMed2001

Na/Li countertransport abnormalities in type 1 diabetes with and without nephropathy are familial.

OBJECTIVE: To determine whether there is a familial abnormality in erythrocyte Na/Li countertransport (CT) kinetics in the approximate one-third of type 1 diabetic patients that succumb to a familial predisposition to nephropathy. RESEARCH DESIGN AND METHODS: Erythrocyte Na/Li CT kinetics were measured in nondiabetic first-degree relatives of type 1 diabetic patients with nephropathy (DNrel) (n = 32) or without nephropathy (DCrel) (n = 22) and normal control subjects ( n = 25). RESULTS: Increases in outside-site Na ion association rate constant and turnover rate of Na/Li countertransport (CT) in DNrels caused increases in Vmax/Km and Vmax, respectively. Thiol alkylation with N-ethy]maleimide (NEM) modifies these kinetic parameters abnormally in nephropathy. With Na ions at the outside site of the transporter, thiol alkylation causes a large decrease in Vmax; but in their absence, Vmax is decreased in normal control subjects, unchanged in DCrels, or increased in DNrels. The relationship between Vmax values after thiol alkylation with or without Na ions was different in DNrels (P < 0.001). Kinetic parameters with and without thiol alkylation identified 60% of DNrels and 20% of DCrels as abnormal. The single-flux rate assay of Na/Li CT did not give this discrimination, and its use may cause discrepancy between studies. CONCLUSIONS: Clinically normal untreated DNrels have the same abnormality in Na/Li CT as the affected patients. DNrels had a metabolic syndrome with increased BMI and plasma triglycerides, but no elevation in blood pressure. Na/Li CT can detect those type 1 diabetic patients at risk of nephropathy who have a familial abnormality in a membrane thiol protein.

Adult↗
PubMed2000

Abnormal thiol group modulation of sodium-lithium countertransport and membrane fluidity is associated with a disturbed relationship between serum triacylglycerols and membrane function in type II diabetes.

In essential hypertension and diabetic nephropathy, sodium-lithium countertransport (Na-Li CT) is an inherited marker, subject to metabolic influences, of cardiovascular risk. Studies in Type II diabetes, taking clinical phenotypes as their starting point, are conflicting. We sought to identify Na-Li CT kinetic abnormalities in Type II diabetes, and only subsequently to seek relationships with clinical variables. Na-Li CT kinetics, membrane fluidity and their modulation by thiol proteins were measured in erythrocytes from 38 patients with Type II diabetes and in 16 normal control subjects. In untreated erythrocytes, Na-Li CT kinetics were similar. Thiol protein alkylation with N-ethylmaleimide generally caused both V(max) and K(m) to fall, but caused K(m) to rise in erythrocytes from 13 out of 38 diabetic subjects, whose native K(m) was low (P=0. 0013 compared with control). V(max) and serum triacylglycerol levels were related in normal controls (r(s)=0.54, P=0.038) and in diabetic subjects whose K(m) fell after N-ethylmaleimide (n=25, r(s)=0.62, P=0.001). Where the K(m) rose after N-ethylmaleimide, V(max) and triacylglycerol levels were not related (n=13, r(s)=-0.39, P=0.183) and membrane fluidity did not increase after N-ethylmaleimide. However, these subgroups were indistinguishable in terms of blood pressure, albuminuria, glycaemia or lipid profiles. Thus abnormalities in the regulation of Na-Li CT and membrane fluidity by key thiol proteins, resembling those seen in essential hypertension and diabetic nephropathy, were apparent in one-third of subjects with Type II diabetes. Membrane abnormalities may indicate a common pathological mechanism. The prognostic significance of Na-Li CT kinetic abnormalities in Type II diabetes must now be confirmed.

Adult↗
PubMed1999

Dysregulation of PMN antigen expression in Type 2 diabetes may reflect a generalized defect of exocytosis: influence of hypertension and microalbuminuria.

Defective exocytosis could underlie clinical and metabolic abnormalities in Type 2 diabetes. Because many SNARE proteins appear to be common mediators of exocytosis, we examined phorbol myristate acetate-stimulated expression of CD11b and CD69 on polymorphonuclear leukocytes (PMN) from Type 2 diabetic subjects with hypertension and microalbuminuria (D-htma), hypertension only (D-ht) or uncomplicated (D-uc), and normal controls (NC) by flow cytometry. CD11b expression was rapid (half maximal by 7 min), initially on all PMN. CD69 expression took place subsequently but on PMN that did not express CD11b. The proportion of CD11b-positive PMN at 30 min was higher in all diabetic groups than in NC. Expression of CD11b was higher and CD69 lower in D-uc and D-htma but were similar in NC and D-ht. In Type 2 diabetes the transition from the CD11b-positive to CD69-positive state is impaired. The defect in the process of CD69 expression appeared most marked in diabetic subjects with hypertension and microalbuminuria.

Adult↗
PubMed1999

Effect of age on plasma membrane asymmetry and membrane fluidity in human leukocytes and platelets.

BACKGROUND: We determined whether ageing changes in plasma membrane phospholipid asymmetry were related to changes in membrane physical characteristics. METHODS: Plasma membrane asymmetry was determined in polymorphonuclear leukocytes (PMN), lymphocytes, and platelets from 45 healthy young (mean 29 years, 26 male) and 28 healthy elderly (mean 70 years, 15 male) subjects by flow cytometric measurement of annexin V binding to cell surface phosphatidylserine. Membrane fluidity in lymphocytes and platelets from young and elderly subjects was determined by fluorescence polarization of 1,6-diphenyl- 1,3,5-hexatriene (DPH) and (4-trimethylammonium)-DPH (TMA). RESULTS: In elderly subjects, a higher proportion of lymphocytes had specific annexin V binding to phosphatidylserine (PS) than in young subjects (young: median percentage of cells with specific annexin V binding to PS 5.3 [second to fourth quintiles range 3.8-8.7]; elderly: 8.5 [5.2-17.2]; p = .028). No ageing change in annexin V binding to PMN was observed (young: 35.0% [21.8-53.5]; elderly: 39.6% [27.4-69.8]; p = .42). Platelets had no specific annexin V binding (young: median molecules of annexin V specific binding 3.8 [0.4-11.3]; elderly: -1.4 [-4.8-1.7]; p = .23). Superficial membrane fluidity was increased in lymphocytes (TMA anisotropy, young: 0.271 [0.259-0.289]; elderly: 0.262 [0.242-0.279];p = .004), but not in platelets (young: 0.273 [0.259-0.293]; elderly: 0.269 [0.248-0.284]; p = .12). Lymphocyte annexin V binding correlated with TMA (r = -.65, p = .022), but not DPH anisotropy (r = -.39, p = .18). CONCLUSIONS: Plasma membrane asymmetry is decreased with age in human lymphocytes, but not in human PMN or platelets. The increased proportion of lymphocytes with loss of plasma membrane asymmetry corresponds to the ageing changes in superficial membrane fluidity observed in lymphocytes. Such alterations in lymphocyte plasma membrane structure with age could account for changes in membrane-bound receptor function described with ageing, and may contribute to alterations in immune responsiveness and vascular thrombosis seen in older humans.

Adult↗
PubMed1999

Thiol protein defect in sodium-lithium countertransport in subset of essential hypertension.

There is probably a heterogeneous etiology for essential hypertension (EHT), and abnormal erythrocyte sodium-lithium countertransport (Na/Li CT) is common in a subgroup of patients with a strong family history of hypertension and cardiovascular disease (EHT-FH patients). The aim of this study was to test the hypothesis that altering a membrane thiol protein could mimic the abnormal Na/Li CT observed in the patients and that a more refined understanding of the mechanism of abnormal Na/Li CT would facilitate a clearer identification of a subgroup of patients with a homogeneous biochemical abnormality. Na/Li CT kinetics were determined in untreated erythrocytes and after thiol group alkylation with N-ethylmaleimide (NEM). Compared with normal control erythrocytes, untreated erythrocytes from EHT-FH patients had a low K(m) of Na/Li CT, with a high ratio of maximum velocity to K(m). This kinetic pattern was reproduced in normal erythrocytes by treatment with NEM in sodium-free medium. The same treatment in EHT-FH erythrocytes caused a markedly abnormal effect with an increase in maximum velocity, indicating an increase in transporter turnover in contrast to the increase in sodium affinity seen in normal control erythrocytes. Frequency distributions of these kinetic changes showed a subgroup of approximately 75% of EHT-FH patients with abnormal kinetic changes with NEM. Therefore, the key Na/Li CT thiol group that is very reactive to NEM and causes the abnormal Na/Li CT in a subgroup of hypertensive patients may be a useful intermediate phenotype for a disease group within the syndrome of EHT. The single flux assay of Na/Li CT at 140 mmol/L sodium poorly discriminates this group. Identification of the thiol protein involved may lead to a molecular explanation of the altered membrane function in this subgroup of patients.

Antihypertensive Agents↗
PubMed1999

Effect of aging on CD11b and CD69 surface expression by vesicular insertion in human polymorphonuclear leucocytes.

The exocytosis of intracellular vesicles is an important function of the plasma membrane, which is responsible for hormone secretion, cell surface expression of antigens, ion transporters and receptors, and intracellular and intercellular signalling. Human aging is associated with many physiological and cellular changes, many of which are due to alterations in plasma membrane functioning. Alterations in vesicle externalization with age could account for many of these changes. We investigated whether alterations in vesicle exocytosis occur with increasing age by flow-cytometric determination of CD11b and CD69 expression on the surface of human polymorphonuclear leucocytes (PMN) stimulated with phorbol myristate acetate (PMA), a tumour promoter which binds to and activates protein kinase C (PKC) directly, or with formyl-Met-Leu-Phe (fMLP), which activates PKC indirectly via interactions with a cell surface receptor and G-protein, and subsequent inositol phosphate hydrolysis. Following stimulation with PMA, a decrease in the proportion of PMN expressing CD69 at high levels was observed in elderly compared with young subjects (young, 55.3%; elderly, 43.9%; P=0.01). No aging-related differences in the proportion of PMN expressing CD11b (young, 73.7%; elderly, 68.4%; P=0.15), or in the number of molecules of CD69 or CD11b expressed per cell, were observed. Stimulation with fMLP or low PMA concentrations resulted in full CD11b expression but minimal CD69 expression in both young and elderly subjects. Cells which expressed CD69 had no CD11b expression, while those cells expressing CD11b had minimal CD69 expression. Thus the PMA-induced expression of CD11b and CD69 in human PMN represents two separate processes, only one of which is affected in aging. CD11b expression appears to require a lesser degree of PKC stimulation compared with that required for CD69 expression. The age-associated reduction in PMA-stimulated CD69 expression may occur either at or distal to PKC activation. Such a decrease may contribute to the age-associated impairments in PMN function that contribute, in turn, to immunosenescence.

Adult↗
PubMed1998

Abnormal regulation of cell membrane fluidity in diabetic nephropathy.

An abnormality of the physical properties of the cell membrane may underlie the defect that unites the clinical and biochemical abnormalities found in subjects with diabetic nephropathy. The cell membrane is linked both structurally and functionally with the cytoskeleton. The fluorescence anisotropy, a measure of membrane fluidity, was studied at baseline and after modulation of cytoskeletal proteins by thiol group alkylation with N-ethylmaleimide (NEM). 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess anisotropy in the deep hydrophobic regions of the lipid bilayer and trimethylammonium-diphenylhexatriene (TMA-DPH) was used to assess the superficial, relatively hydrophilic regions. We compared 17 subjects with insulin-dependent diabetes mellitus (IDDM) and nephropathy with 17 control subjects with IDDM and 24 non-diabetic control subjects. Median TMA-DPH anisotropy (0.271 (0.239-0.332) vs 0.269 (0.258-0.281) vs 0.275 (0.246-0.287)) and DPH anisotropy (0.221 (0.193-0.261) vs 0.227 (0.197-0.253) vs 0.226 (0.193-0.245)) were similar in erythrocytes from the three groups. However after alkylation of protein thiol groups with NEM clear differences emerged. In the control subjects with and without IDDM there was a significant fall in TMA-DPH anisotropy compared to the subjects with diabetic nephropathy in whom the addition of NEM had no effect (deltaTMA-DPH anisotropy -0.005 (-0.020 - +0.006) vs -0.005 (-0.011 - +0.016) vs +0.002 (-0.010 - +0.008) p < 0.001). This finding was confirmed when the deep regions of the lipid bilayer were assessed using DPH (deltaDPH anisotropy -0.017 (-0.029 - -0.007.) vs -0.015 (-0.029 - +0.001) vs + 0.003 (-0.021 - +0.018) p < 0.001). We conclude that cytoskeletal modulation of the physical properties of the cell membrane lipids by proteins is abnormal in subjects with diabetic nephropathy. Such an abnormality could explain some of the clinical and metabolic abnormalities found in this condition.

Adult↗
PubMed1998

Erythrocyte membrane thiol proteins associated with changes in the kinetics of Na/Li countertransport: a possible molecular explanation of changes in disease.

BACKGROUND: Abnormal erythrocyte Na/Li countertransport is associated with diseases such as essential hypertension and diabetic renal disease. Although it seems unlikely that Na/Li countertransport contributes to any disease process, it may be abnormal because of a change in the cell membrane that is part of the disease process. METHODS: We have shown that Na/Li countertransport kinetics are modified by two types of thiol group. One of these, which we have called 'type 1', is rapidly alkylated by N-ethylmaleimide to give a kinetic pattern similar to that in the above diseases. RESULTS: AtpH 6 and 2 degrees C, both N-ethylmaleimide and iodoacetamide cause the K(m) of Na/Li countertransport to decrease to completion in 300s, with 78% (SEM 6%) of the decrease occurring in 30s. Using these reaction conditions, N-ethylmaleimide reacted with a unique thiol group on a 33-kD protein, blocking its subsequent reaction with biotin maleimide. This 33-kD protein was present in rabbit erythrocytes, which have high levels of Na/Li countertransport, but absent from rat erythrocytes, which have no Na/Li countertransport. Iodoacetyl biotin labelled a 60-kD protein that was specifically blocked by iodoacetamide. CONCLUSION: We suggest that these proteins are members of a cluster of membrane proteins that can modify Na/Li countertransport and may have a functional role in the disease processes.

Adult↗
PubMed1998

Sodium-lithium countertransport: physiology and function.

Current opinions on the relationships between erythrocyte sodium-lithium countertransport kinetics and primary hypertension, hyperlipidaemia and diabetic nephropathy are reviewed. Problems associated with the assay are analysed. Some possible mechanisms that could modify the kinetics of ion exchange are examined. The question of what catalyses sodium-lithium countertransport is discussed, but not answered. Some models are put forward showing how a study of sodium-lithium countertransport kinetics could further our understanding of important disease processes.

Animals↗