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Inyeong Choi - One of the best experts on this subject based on the ideXlab platform.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Peijian He, Ira Rajbhandari, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3 transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pHo 7.4. At pHo 6.5, the intracellular pH of neurons was ~1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo 6.5. NBCn1 expression also increased by 40% in a prolonged Mg 2+ -free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mM glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo 7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg 2+ -free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHo and Mg 2+ Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg 2+ -free conditions.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Ira Rajbhandari, Eunjin Kim, Chris C Yun, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO(3) transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pH(o)) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pH(o) 7.4. At pH(o) 6.5, the intracellular pH of neurons was approximately 1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pH(o) 6.5. NBCn1 expression also increased by 40% in a prolonged Mg(2+)-free incubation at normal pH(o). Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pH(o) 7.2 for 6 h) after glutamate exposure, acidic incubation (pH(o) 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg(2+)-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pH(o) and Mg(2+) Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg(2+)-free conditions.
Burton M Altura - One of the best experts on this subject based on the ideXlab platform.
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Magnesium Depletion impairs myocardial carbohydrate and lipid metabolism and cardiac bioenergetics and raises myocardial calcium content in vivo relationship to etiology of cardiac diseases
Iubmb Life, 1996Co-Authors: Burton M Altura, Asefa Gebrewold, Bella T Altura, Nachman BrautbarAbstract:This study examines the effects of Mg Depletion on myocardial bioenergetic, carbohydrate, lipid and phospholipid metabolism. Rats were studied after long-term (12 week) selective dietary restriction of Mg (20% normal dietary intake). Myocardial biopsy samples were examined for glucose 6-phosphate and glycogen to evaluate carbohydrate pathways and for glycerol phosphate and mitochondrial fatty acid oxidation and phospholipid contents to evaluate lipid and phospholipid turnover. Dietary Mg deficiency resulted in falls in myocardial glycogen, glucose-6-phosphate, glycerol phosphate, as well as the contents of phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidyl glycerol (DPG), phosphatidyl inositol (PI) and total phospholipid phosphorus. These observations demonstrate impaired phospholipid metabolism, probably at the biosynthetic level. The mitochondrial oxidation of long-chain fatty acids was also impaired after Mg Depletion. Mg Depletion (serum Mg fell 60%) also resulted in significant falls in myocardial [ATP], phosphocreatine (PCr), and Mg with a concomitant rise in myocardial Ca content. These observations are consistent with the tenet that prolonged low [Mg2+]zero can result in marked reduction in oxygen and substrate delivery to the cardiac myocytes, with concomitant changes in membrane phospholipids (potentially resulting in a pro-oxidant state) probably as a result of coronary vasoconstriction.
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extracellular and intracellular Magnesium Depletion in pregnancy and gestational diabetes
American Journal of Obstetrics and Gynecology, 1995Co-Authors: Mordechai Bardicef, Orit Bardicef, Yoram Sorokin, Burton M Altura, David B Cotton, Lawrence M ResnickAbstract:OBJECTIVE: Our purpose was to investigate a possible ionic basis linking pregnancy and gestational diabetes with the vascular disorders associated with them. STUDY DESIGN: We used phosphorus 31 nuclear magnetic resonance spectroscopy and Magnesium- and calcium-specific ion electrodes to measure erythrocyte intracellular free Magnesium, plasma ionized Magnesium, and ionized calcium in fasting nonpregnant (n = 26), normal pregnant (n = 20), and diet-controlled (class A1) gestational diabetic women (n = 13). RESULTS: Compared with nonpregnant controls (total Magnesium 0.91 ± 0.07 mmol/L, ionized Magnesium 0.51 ± 0.03 mmol/L), total and ionized Magnesium 0.46 ± 0.02 mmol/L, significance < 0.0001) and gestational diabetic (total Magnesium 0.74 ± 0.05 mmol/L, ionized Magnesium 0.46 ± 0.02 mmol/L, significnce < 0.0001) subjects. Gestational diabetic women had significantly lower intracellular free Magnesium values compared with nonpregnant and normal pregnant individuals (140 ± 20 μmol/L vs 169 ± 27 μmol/L, significance = 0.007). Ionized calcium values were similar in all groups, resulting in significant elevation (significance < 0.0001) of ionized calcium/ionized Magnesium ratios in both pregnant groups. CONCLUSIONS: These results support the presence of Magnesium Depletion in pregnancy itself and to a greater extent in gestational diabetes. We suggest that Magnesium Depletion, or relative calcium excess, may predispose to vascular complications of pregnancy.
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intracellular and extracellular Magnesium Depletion in type 2 non insulin dependent diabetes mellitus
Diabetologia, 1993Co-Authors: Lawrence M Resnick, Burton M Altura, Raj K Gupta, John H Laragh, Michael H AldermanAbstract:To investigate alterations of Magnesium metabolism in Type 2 (non-insulin-dependent) diabetes mellitus, we utilized a new Magnesium-specific selective ion electrode apparatus to measure serum ionized Magnesium (Mg-io) in fasting subjects with and without Type 2 diabetes, and compared these values to levels of serum total Magnesium, and of intracellular free Magnesium (Mgi) analysed by 31P-NMR spectroscopy. Both Mg-io (0.630±0.008 vs 0.552± 0.008 mmol/l, p<0.001) and Mgi (223.3±8.3 vs 184± 13.7 mmol/l,p<0.001), but not serum total Magnesium, were significantly reduced in Type 2 diabetes compared with nondiabetic control subjects. Furthermore, a close relationship was observed between serum Mg-io and Mgi (r=0.728, p<0.001). We suggest that Magnesium deficiency, both extracellular and intracellular, is a characteristic of chronic stable mild Type 2 diabetes, and as such, may predispose to the excess cardiovascular morbidity of the diabetic state. Furthermore, by more adequately reflecting cellular Magnesium metabolism than total serum Magnesium levels, Mg-io measurements may provide a more readily available tool than has heretofore been available to analyse Magnesium metabolism in a variety of diseases.
Deborah S Cooper - One of the best experts on this subject based on the ideXlab platform.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Peijian He, Ira Rajbhandari, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3 transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pHo 7.4. At pHo 6.5, the intracellular pH of neurons was ~1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo 6.5. NBCn1 expression also increased by 40% in a prolonged Mg 2+ -free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mM glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo 7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg 2+ -free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHo and Mg 2+ Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg 2+ -free conditions.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Ira Rajbhandari, Eunjin Kim, Chris C Yun, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO(3) transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pH(o)) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pH(o) 7.4. At pH(o) 6.5, the intracellular pH of neurons was approximately 1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pH(o) 6.5. NBCn1 expression also increased by 40% in a prolonged Mg(2+)-free incubation at normal pH(o). Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pH(o) 7.2 for 6 h) after glutamate exposure, acidic incubation (pH(o) 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg(2+)-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pH(o) and Mg(2+) Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg(2+)-free conditions.
Han Soo Yang - One of the best experts on this subject based on the ideXlab platform.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Peijian He, Ira Rajbhandari, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3 transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pHo 7.4. At pHo 6.5, the intracellular pH of neurons was ~1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo 6.5. NBCn1 expression also increased by 40% in a prolonged Mg 2+ -free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mM glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo 7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg 2+ -free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHo and Mg 2+ Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg 2+ -free conditions.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Ira Rajbhandari, Eunjin Kim, Chris C Yun, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO(3) transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pH(o)) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pH(o) 7.4. At pH(o) 6.5, the intracellular pH of neurons was approximately 1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pH(o) 6.5. NBCn1 expression also increased by 40% in a prolonged Mg(2+)-free incubation at normal pH(o). Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pH(o) 7.2 for 6 h) after glutamate exposure, acidic incubation (pH(o) 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg(2+)-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pH(o) and Mg(2+) Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg(2+)-free conditions.
Ira Rajbhandari - One of the best experts on this subject based on the ideXlab platform.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Peijian He, Ira Rajbhandari, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3 transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pHo 7.4. At pHo 6.5, the intracellular pH of neurons was ~1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo 6.5. NBCn1 expression also increased by 40% in a prolonged Mg 2+ -free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mM glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo 7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg 2+ -free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHo and Mg 2+ Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg 2+ -free conditions.
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sodium bicarbonate cotransporter nbcn1 slc4a7 increases cytotoxicity in Magnesium Depletion in primary cultures of hippocampal neurons
European Journal of Neuroscience, 2009Co-Authors: Deborah S Cooper, Han Soo Yang, Ira Rajbhandari, Eunjin Kim, Chris C Yun, Inyeong ChoiAbstract:Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO(3) transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pH(o)) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pH(o) 7.4. At pH(o) 6.5, the intracellular pH of neurons was approximately 1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pH(o) 6.5. NBCn1 expression also increased by 40% in a prolonged Mg(2+)-free incubation at normal pH(o). Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pH(o) 7.2 for 6 h) after glutamate exposure, acidic incubation (pH(o) 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg(2+)-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pH(o) and Mg(2+) Depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg(2+)-free conditions.
