The Na+, K+-ATPase (NKA) is an ubiquitous enzyme consisting of α, β and γ subunits, and is responsible for the creation and maintenance of the Na+ and K+ gradients across the cell membrane by transporting 3 Na+ out and 2 K+ into the cell. Sodium pump regulation is tissue as well as isoform specific. Intracellular messengers differentially regulate the activity of the individual NKA isozymes. Regulation of specific NKA isozymes gives cells the ability to precisely coordinate NKA activity to their physiological requirements. It is the only known receptor for the cardiac glycosides used to treat congestive heart failure and cardiac arrhythmias. Endogenous ligands structurally similar to cardiac glycosides may act as natural regulators of the sodium pump in heart and other tissues. Identification of naturally occurring regulators of NKA could initiate the discovery of new hormone-like control systems involved in the etiology of selected disease processes, hence the importance of understanding the relation of the sodium pump and its ligands to disease. Diabetes has a marked effect on the metabolism of a variety of tissues and because the NKA is critical for the membrane potential and many transports, a change in its activity in diabetes would have profound consequence in these tissues. NKA is also involved in hypertension, salt balance, cardiovascular and renal disorders, sperm capacitation, cell volume regulation, apoptosis, rheumatoid arthritis, sepsis, neurological disorders, lung edema clearance and preeclampsia. NKA activity and expression in the collecting duct of kidney are modulated physiologically by hormones like aldosterone, vasopressin, and insulin. NKA enzyme activity and subunit levels are reduced in carcinoma, NKA-β levels were highly reduced in an invasive form of human renal clear cell carcinoma, androgen-dependent prostate cancer, in early stages of urothelial cancer, as well as in poorly differentiated, highly motile carcinoma cell lines obtained from various tissues suggesting a functional link between reduced NKA-β expression and cancer progression. It could be a target for the development of anticancer drugs as it serves as a signal transducer, it is a player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers.KeywordsNa+, K+-ATPase (NKA); Cardiotonic steroids (CTS); Diabetes; Hypertension; Cardiovascular and renal disorders; Signal transducer; Anticancer drugs
BackgroundInconsistent reports are available in the literature regarding the oxidative status and antioxidant capacity during the pathogenesis of gestational diabetes. Present study was aimed to evaluate oxidative stress during the development of gestational diabetes and to evaluate antioxidant capability in non-pregnant (control), pregnant and gestational diabetics.MethodsThe study consisted of non-pregnant, healthy pregnant and patients suffering from gestational diabetes mellitus (GDM). Each group consisted of 23 women. We compared their oxidative and anti-oxidative system in blood. Their blood malondialdehyde (MDA) and antioxidant vitamins (C, E, A) were determined and compared to evaluate the oxidative status and anti-oxidative capacity of these groups. We have also compared the osmotic fragility profiles of the erythrocytes of these groups.ResultsPlasma MDA content in pregnant was significantly higher compared to non-pregnant (p < 0.001, 67.5%) and even in gestational diabetics; its value was found significantly further elevated (p = 0.001, 13.8%) compared to healthy pregnant. There was significant decline (p < 0.001, 41.9%) in the level of vitamin C in pregnant as compared to non-pregnant. Although in GDM the decrease was significant (p = 0.025, 20.6%) but comparatively lesser when compared to healthy pregnant. Vitamin E showed the increase of 9.6% during pregnancy, although this alteration was non-significant (p = 0.09), but the level was found to decline significantly (p < 0.001, 25.5%) in GDM compared to pregnant group. Vitamin A contents were also decreased in pregnant (p = 0.002, 17.4%) compared to non-pregnant and in GDM (p = 0.012, 11.2%) compared to pregnant group. Osmotic fragility (O.F.) profiles showed insignificant (p = 0.325) enhanced mean erythrocyte fragility (MEF) in pregnant but this increase was significant (p = 0.003) in case of GDM. The O.F. profiles of pregnant and GDM erythrocytes got shifted to the right side of the control one.ConclusionsOur findings indicate highly enhanced lipid peroxidation and significant depletion in antioxidant capacity during the development of gestational diabetes, and these alterations are not the cause but the consequence of GDM. However, further studies are warranted to examine a wider range of biochemical parameters to evaluate the potential risks of oxidative damage in GDM.KeywordsGestational diabetes; Oxidative stress; Anti-oxidants; Vitamins C, E, A; Osmotic fragility; Non-pregnant; Pregnant; GDM
BackgroundAn increased oxidative level and decreased antioxidant activities in the blood of preeclamptic women have been reported by us and other workers. The present study was aimed to evaluate oxidative stress in infants born to preeclamptic mothers, and to examine whether cord blood with oxygen radical disease had different total enzymatic antioxidant status than those without preeclampsia.MethodsThe present study consisted of 23 normotensive (served as control) and 23 preeclamptic mothers. We compared their oxidative and anti-oxidative system in maternal and cord blood of pair-matched mother and neonate. Their blood malondialdehyde (MDA), antioxidant enzymes were determined and compared to evaluate if pro-oxidative status of preeclampsia differs from the status in cord blood of pair-matched neonate.ResultsThe MDA content in preeclamptic maternal plasma was significantly high (p < 0.001) compared to that of control. Interestingly, its content in preeclamptic cord blood was significantly low (p < 0.001) compared to their pair-matched maternal blood. Superoxide dismutase (SOD) activity was 8.7% higher in cord as compared to pair-matched normotensive maternal blood which was significant (p = 0.01) whereas in preeclamptic cord the level decreased significantly (p = 0.011) in comparison to pair-matched preeclamptic maternal. Glutathione peroxidase (GPx) was 16.4% higher in normotensive cord compared to maternal blood, and 7% low in preeclamptic cord compared to pair-matched maternal blood. The increase was significant (P = 0.011) in normotensive cord whereas in preeclamptic cord the decrease was insignificant (p = 0.06). Contrary to earlier reports on catalase activity, our results showed 20.97% elevation in normotensive and 16.12% increase in the preeclamptic cord blood compared to their pair-matched maternal blood. This change was significant with p = 0.01 and p = 0.017 in control and preeclamptic group respectively.ConclusionsOur results showed the significantly low MDA contents in the pair-matched cord blood and the activities of SOD, GPx and Catalase mentioned above, we conclude that the oxidative stress status is low in the blood of neonates born to preeclamptic mothers. Further studies are needed to explore strategies so that the normal levels of antioxidant vitamins are maintained to combat preeclampsia in women at high risk.KeywordsMaternal; Cord blood; Malondialdehyde; Antioxidant enzymes; Glutathione peroxidase; Glutathione reductase; Superoxide dismutase; Catalase
1. The erythrocyte membrane acetylcholinesterase activity is significantly (P less than 0.001) decreased in insulin-dependent diabetes mellitus. 2. The activity is negatively correlated (r = -0.97) with the fasting blood glucose level. 3. Insulin treatment restores the activity to normal. 4. The Km of the enzyme for acetylthiocholine iodide was unchanged; however, the Vmax. was decreased, suggesting a decrease in the number of active enzyme molecules in diabetes.
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