Ouabain-insensitive, Na-ATPase activity in pure suspensions of rat kidney proximal tubules

AbstractThe present work was undertaken to evaluate the distribution of the Na-ATPase activity in the different components of the rat kidney cortex. Suspensions of glomeruli, proximal and distal tubules were prepared following a collagenase digestion of outermost kidney cortex slices and a separation on a Percoll gradient. It was found that the Na-ATPase activity is higher in the fraction enriched in proximal tubules. The fraction enriched in glomeruli and in distal tubules show also a Na-ATPase activity, but it is lower

Can magnesium gluconate be used as an alternative therapy for preeclampsia?

Magnesium (Mg+2) in the body plays a structural and regulatory role and it is involved in fundamental cellular reactions. It is known that Mg+2 blood levels decrease during pregnancy, which has been related to preeclampsia and premature delivery, as well as other pathologies such as cardiovascular alterations and renal, gastrointestinal, neurological, and muscular dysfunctions among others. Mg+2 salts are used to treat its deficiency, and parenteral magnesium sulfate (MgSO4) is relatively effective in preeclampsia and eclampsia. The use of MgSO4 has the main disadvantage that it is mainly administered intravenously which leads to significant toxicity risks. Currently, other magnesium salts are being studied as alternative treatments. Magnesium gluconate (Mg-gluconate) has been used to prevent pregnancy-induced hypertension, showing a greater antioxidant capacity than MgSO4. Mg-gluconate can scavenge hydroxyl and alkoxyl radicals and it has been shown that it can inhibit lipid peroxidation in microsomal membranes treated in vitro with the Fenton reaction. Mg-gluconate seems to be an excellent candidate to replace MgSO4 as a therapy for preeclampsia with severe features.El magnesio (Mg+2) en el organismo, juega un papel estructural y regulador, y participa en reacciones celulares fundamentales. Se sabe que los niveles séricos de Mg+2 disminuyen durante el embarazo, lo cual se ha relacionado con la preeclampsia y el parto prematuro, así como con otras patologías como alteraciones cardiovasculares y disfunciones renales, gastrointestinales, neurológicas, musculares, entre otras. Las sales de Mg+2 se utilizan para tratar su deficiencia, y el sulfato de magnesio parenteral (MgSO4) ha demostrado ser relativamente eficaz en la preeclampsia y la eclampsia. El uso de MgSO4 tiene el principal inconveniente de que se administra principalmente por vía intravenosa, lo cual conlleva a riesgos importantes de toxicidad. Actualmente, se están estudiando otras sales de magnesio como tratamientos alternativos. El gluconato de magnesio (Mg-gluconato) se ha utilizado para prevenir la hipertensión inducida por el embarazo, mostrando una mayor capacidad antioxidante que el MgSO4. El Mg-gluconato es capaz de eliminar radicales hidroxilo y alcoxilo e inhibir la peroxidación lipídica en membranas microsomales tratadas in vitro con la reacción de Fenton. El Mg-gluconato parece ser un excelente candidato para sustituir al MgSO4 como terapia para la preeclampsia con características graves.Sociedad Argentina de Fisiologí

On the functional use of the membrane compartmentalized pool of ATP by the Na+ and Ca++ pumps in human red blood cell ghosts

Previous evidence established that a sequestered form of adenosine triphosphate (ATP pools) resides in the membrane/cytoskeletal complex of red cell porous ghosts. Here, we further characterize the roles these ATP pools can perform in the operation of the membrane's Na+ and Ca2+ pumps. The formation of the Na+- and Ca2+-dependent phosphointermediates of both types of pumps (ENa-P and ECa-P) that conventionally can be labeled with trace amounts of [γ-3P]ATP cannot occur when the pools contain unlabeled ATP, presumably because of dilution of the [γ-3P]ATP in the pool. Running the pumps forward with either Na+ or Ca2+ removes pool ATP and allows the normal formation of labeled ENa-P or ECa-P, indicating that both types of pumps can share the same pools of ATP. We also show that the halftime for loading the pools with bulk ATP is 10–15 minutes. We observed that when unlabeled “caged ATP” is entrapped in the membrane pools, it is inactive until nascent ATP is photoreleased, thereby blocking the labeled formation of ENa-P. We also demonstrate that ATP generated by the membrane-bound pyruvate kinase fills the membrane pools. Other results show that pool ATP alone, like bulk ATP, can promote the binding of ouabain to the membrane. In addition, we found that pool ATP alone functions together with bulk Na+ (without Mg2+) to release prebound ouabain. Curiously, ouabain was found to block bulk ATP from entering the pools. Finally, we show, with red cell inside-outside vesicles, that pool ATP alone supports the uptake of 45Ca by the Ca2+ pump, analogous to the Na+ pump uptake of 22Na in this circumstance. Although the membrane locus of the ATP pools within the membrane/cytoskeletal complex is unknown, it appears that pool ATP functions as the proximate energy source for the Na+ and Ca2+ pumps

Patogenia de la preeclampsia

La preeclampsia afecta alrededor del 7 % de las gestantes que dan a luz y es la primera causa de morbilidad y mortalidad maternofetal mundial . En la gestante, la enfermedad produce disfunción endotelial difusa y plaquetaria, manifestándose con hipertensión arterial (HTA), proteinuria y edema. En el feto, la condición se asocia a deprivación nutricional o respiratoria, caracterizándose por centralización del flujo sanguíneo, restricción del crecimiento intrauterino e incluso, la muerte