الرجاء استخدام هذا المفتاح للوصول الى هذا العنصر: http://hdl.handle.net/123456789/187
العنوان: Reduced Nucleoside Transport Activity and Lowered hENT1 Protein Expression in Glucose 6-Phosphate Dehydrogenase-deficient Erythrocytes
المؤلفون: Mohammed Alansari محمد عبدالرحمن علي الانصاري 
Supervisor: د. جيمس كريك
الموضوع: Glucose 6-Phosphate Dehydrogenase-deficient Erythrocytes
تاريخ الاصدار: 2012
الناشر:  Kuwait university - college of graduate studies
ملخص: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that can cause haemolytic anaemia. It is the most prevalent inherited enzyme deficiency worldwide and is one of the most common hematologic disorders in Kuwait (5.5% of total population in year 2000) and the Middle East (from 1- 39%). G6PD catalyse the first, rate-limiting, step in the pentose phosphate pathway that produces NADPH, which acts by reducing glutathione, an important cellular component that protects erythrocytes from oxidative damage. Deficiency of G6PD puts patients at risk of haemolytic episodes in response to certain foods, pharmaceuticals and infections. Pathologies associated with G6PD deficiency are variable, suggesting that additional factors may contribute to clinical responses. The project aim was to investigate membrane changes that might contribute to red cell pathology in G6PD deficiency. SDS-PAGE, immunoblotting and radioactive uridine cellular uptake techniques were applied to samples from G6PD-deficient individuals and normal controls. SDS-PAGE demonstrated no major differences in membrane protein profile. However, immunoblot analysis showed marked and variable decrease in hENT1 nucleoside transporter expression (mean 48.8%, 95% CI 36.1-61.4%, p=0.007) while expression of glucose transporter (Glut1) and anion exchanger AE-1 (‘Band 3’) polypeptides showed no significant changes (mean 107.1%, 95% CI 94.2-119.9%, p=0.296, mean 98.6%, 95% CI 96.4-100.7%, p=0.204 respectively). 3H-Uridine uptake at 64nM showed significant (p=0.031) and variable reduction in uptake in G6PD-deficient erythrocytes (mean 8.18, 95% CI 5.6-10.7) compared to control cells (mean 12.35, 95% CI 9.2-15.5) at 25 C° (units: pmol/g Hb/min). The discovery that many G6PD-deficient patients have substantially lower hENT1 expression and show decreased nucleoside uptake suggests that this could be an important additional factor that may influence red cell biochemistry and physiology and which should be considered in the assessment and treatment of G6PD-deficient subjects. The cause(s) of the changes in hENT1 expression remain(s) to be determined.
URI: http://hdl.handle.net/123456789/187
يظهر في المحتويات:0540 Medical Biochemistry (M.Sc.)

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