Inhibition of K+ efflux and dehydration of sickle cells by [(dihydroindenyl)oxy]alkanoic acid: an inhibitor of the K+ Cl- cotransport system.

Vitoux, Dominique; Olivieri, Oliviero; Garay, Ricardo P.; Cragoe, Edward J.; Galactéros, F; Beuzard, Yves

doi:10.1073/pnas.86.11.4273

Cited by 47 publications

(30 citation statements)

References 19 publications

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“…3,18,19,21 Studies in diseased red cells have shown that KCC plays a crucial role in red cell volume regulation, contributing to red cell water and K + loss and generation of dehydrated red cells.…”

Section: 16-20mentioning

confidence: 99%

“…10,11 In red cells, the KCC function is modulated by cell swelling, cell acidification, reduced cell magnesium (Mg) content, membrane oxidative damage and cell age. 3,[16][17][18][19][20] Abnormal activation of KCC has been reported in sickle red cells, in β thalassemic syndromes and in pathological erythrocytes containing positively charged hemoglobin variants in β6 and β7. 3,18,19,21 Studies in diseased red cells have shown that KCC plays a crucial role in red cell volume regulation, contributing to red cell water and K + loss and generation of dehydrated red cells.…”

Section: -4mentioning

confidence: 99%

“…3,[16][17][18][19][20] Abnormal activation of KCC has been reported in sickle red cells, in β thalassemic syndromes and in pathological erythrocytes containing positively charged hemoglobin variants in β6 and β7. 3,18,19,21 Studies in diseased red cells have shown that KCC plays a crucial role in red cell volume regulation, contributing to red cell water and K + loss and generation of dehydrated red cells. 3,20,22 Recently KCC1, 3 and 4 have been described in human reticulocytes and in human erythroid precursors from sickle cell subjects.…”

Section: -4mentioning

confidence: 99%

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K-CL co-transport plays an important role in normal and thalassemic erythropoiesis

Franceschi¹,

Ronzoni²,

Cappellini³

et al. 2007

Haematologica

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Background and ObjectivesCell volume changes are hallmarks of both cell maturation and apoptosis, and are paralleled by modulation of membrane ion transport pathways. We evaluated the possible role of K-Cl co-transport (KCC) in both normal and β-thalassemic erythropoiesis in vitro. Design and MethodsWe studied the effects of the KCC inhibitor, DIOA, on cell proliferation and differentiation, on expression of KCC mRNA and polypeptides, and on expression of cell cycle and apoptosis genes in in vitro liquid-cultures of CD34 + cells from normal and β-thalassemic subjects. Resultsβ-thalassemic erythroid precursors showed increased abundance of KCC1-3 mRNA and of KCC polypeptides in late erythropoiesis. DIOA markedly modified the composition of normal erythroid precursors, promoting differentiation and arrest at the polychromatic erythroblast stage and resulting in a precursor distribution profile similar to that of untreated β-thalassemic cells. DIOA up-regulated cyclin-D mRNA levels in late erythropoiesis in both cell models, paralleling changes in the percentage of S-phasecells. Caspase-3 activity in late erythropoiesis declined to similar degrees in both cell models. DIOA did not modify caspase-3 or -8 mRNA levels. Interpretation and ConclusionsIneffective erythropoiesis of in vitro cultured β-thalassemic cells is likely related to impaired cell maturation. KCC activity appears to contribute to erythroid cell growth during late erythropoiesis. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n E rythropoiesis is a complex multistage process characterized by differentiation of pluripotent hematopoietic progenitors to reticulocytes and then to mature red cells. Although understanding of the mechanisms involved in the maturation of normal erythroid precursors has progressed in the last decade, much remains unknown about erythroid maturation in inherited erythroid diseases. β thalassemia is a congenital red cell disorder characterized by the absence or reduced synthesis of hemoglobin β globin chains. Despite extensive knowledge of the molecular defects causing β thalassemia, less is known about the major factors contributing to β thalassemic anemia: the reduction of β thalassemic red cell life-span and ineffective erythropoiesis. 1-4Ineffective erythropoiesis has been shown in β thalassemia in vivo by ferrokinetic assays, suggesting a block in erythroid precursors and a precocious cell death in bone marrow.2-5 Recently, Mathias et al. showed that ineffective erythropoiesis in the bone marrow precursors of patients with β thalassemia major is associated with progressively increased apoptosis of polychromatophilic normoblasts of late erythropoiesis and seems to be related to hemoglobin chain synthesis.6 However, the mechanisms underlying apoptosis of β thalassemic erythroid precursors and the developmental kinetics of β thalassemic ineffective erythropoiesis need further investigation.Since cell volume change is one of the hallmarks of cell progression towards apoptosis or proliferation, the modulation of ion tran...

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Section: 16-20mentioning

confidence: 99%

Section: -4mentioning

confidence: 99%

Section: -4mentioning

confidence: 99%

See 1 more Smart Citation

K-CL co-transport plays an important role in normal and thalassemic erythropoiesis

Franceschi¹,

Ronzoni²,

Cappellini³

et al. 2007

Haematologica

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“…Cl -) co-transport system was proposed to be involved in cell potassium (K ? ) loss and dehydration [13]. Deoxygenation of sickle cell is known to increase cation permeability of sodium (Na ?…”

Section: Introductionmentioning

confidence: 99%

Biochemical Indicator of Sickle Cell Disease: Preliminary Report from India

et al. 2011

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Blood biochemistry has significant effect on pathophysiology of human body. Recently few studies found the association of biochemical abnormalities in sickle cell patients. Sickle cell disease showed clinical variability where African ancestors have severe phenotype than Indian sicklers. Our aim was to evaluate the biochemicals in sickle cell patients and their effect on severity. Here we present the comparative biochemical levels in sickle cell patients as well as controls. Sickle cell patients diagnosed by HPLC and biochemical analysis done by Beckman-auto analyzer. T test applied for statistical analysis. Result showed the renal abnormality lesser in patients and related biochemical within the normal range and statistically not significant. Electrolytes, hepatic enzymes, alkaline phosphatase and glucose were elevated and statistically significant (P value \0.05). Observation of the study concludes the biochemical abnormality play a significant role in sickle cell patient's physiopathology and can be used to management of the disease.

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“…When serum creatinine is elevated the disease has reached an advanced stage and lead to renal failure. Deoxygenation of sickle cell is known to increase cation permeability of sodium (Na + ), potassium (K + ) and calcium (Ca 2+ ) (Vitoux et al, 1989;Rhoda et al, 1990;Gibson et al, 1998). Urea, an end product of protein metabolism, is excreted by the kidney.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Some Biochemical Parameters in Subject with HbSC and HbSS in Saki West Local Government - a Rural Community in Nigeria

Olaniyan¹

2016

Am. J. Biomed. Sci.

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Background: HbSS and HbSC are a group of genetic blood disorders. They are examples of sickle cell diseases.The complication of sickle cell disease could affect spleen, brain, eyes, lungs, liver, heart, kidneys, penis, joints, bones, or skin. Aim and Objective: This work was designed to measure plasma ALT, AST, Albumin,Se, Zn and Uric acid in HbSS and HbSC patients in Saki-West Local Government area of Oyo state-Nigeria. Materials and Methods: HbSS and HbSC patients in crisis and in non-crisis steady state classified into HbSC (n=25) and HbSS (n=25) aged 10 to 31 years were recruited as test subjects for the study. Apparently healthy 50 HbAA volunteers classified into female (n=25) and male (n=25) aged 10 -50 years were also studied as control. Subjects residing in Saki-West for not less than 5 years were recruited as test and control subjects. Plasma Albumin, Uric acid, ALT(Alanine Transaminase), AST(Aspartate Trans aminase) were determined biochemically bt spectrophotometry.Plasma Zn (Zinc) and Se (Selenium) were measured by Atomic Absorption Spectrophotometry. Results: The result obtained showed a significantly higher mean value of plasma ALT and AST in HbSC and HbSS than HbAA with p<0.05. The result also showed a significantly lower plasma selenium mean value in HbSC and HbSS than HbAA with p<0.05 This biochemical alterations including plasma Zn was more in crisis than in non-crisis steady state. Conclusion and Recommendation: Decreased plasma level of Selenium and increased plasma AST and ALT were found in HbSS and HbSC patients. This biochemical alterations including plasma Zn was more in crisis than in non-crisis steady state.

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Inhibition of K+ efflux and dehydration of sickle cells by [(dihydroindenyl)oxy]alkanoic acid: an inhibitor of the K+ Cl- cotransport system.

Cited by 47 publications

References 19 publications

K-CL co-transport plays an important role in normal and thalassemic erythropoiesis

K-CL co-transport plays an important role in normal and thalassemic erythropoiesis

Biochemical Indicator of Sickle Cell Disease: Preliminary Report from India

Investigation of Some Biochemical Parameters in Subject with HbSC and HbSS in Saki West Local Government - a Rural Community in Nigeria

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