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1.
Leucio D Vieira‐Filho Lucienne S Lara Paulo A Silva Ricardo Luzardo Marcelo Einicker‐Lamas Henriqueta D Cardoso Ana DO Paixão Adalberto Vieyra 《Clinical and experimental pharmacology & physiology》2009,36(12):1157-1163
- 1 Intrauterine malnutrition has been linked to the development of adult cardiovascular and renal diseases, which are related to altered Na+ balance. Here we investigated whether maternal malnutrition increases placental oxidative stress with subsequent impact on renal ATP‐dependent Na+ transporters in the offspring.
- 2 Maternal malnutrition was induced in rats during pregnancy by using a basic regional diet available in north‐eastern Brazil. Placental oxidative stress was evaluated by measuring thiobarbituric acid‐reactive substances, which were 35–40% higher in malnourished dams (MalN). Na+ pumps were evaluated in control and prenatally malnourished rats (at 25 and 90 days of age).
- 3 Identical Na+/K+‐ATPase activity was found in both groups at 25 days (approximately 150 nmol Pi/mg per min). However, although Na+/K+‐ATPase increased by 40% with growth in control rats, it remained constant in pups from MalN.
- 4 In juvenile rats, the activity of the ouabain‐insensitive Na+‐ATPase was higher in MalN than in controls (70 vs 25 nmol Pi/mg per min). Nevertheless, activity did not increase with kidney and body growth: at 90 days, it was 50% lower in MalN than in controls. The maximal stimulation of the Na+‐ATPase by angiotensin (Ang) II was 35% lower in MalN than in control rats and was attained only with a much higher concentration of the peptide (10?10 mol/L) than in controls (10?14 mol/L).
- 5 Protein kinase C activity, which mediates the effects of AngII on Na+‐ATPase was only one‐third of normal values in the MalN group.
- 6 These results indicate that placental oxidative stress may contribute to fetal undernutrition, which leads to later disturbances in Na+ pumps from proximal tubule cells.
2.
Toklu HZ Sehirli O Erşahin M Süleymanoğlu S Yiğiner O Emekli-Alturfan E Yarat A Yeğen BÇ Sener G 《The Journal of pharmacy and pharmacology》2010,62(12):1784-1793
Objectives The putative protective effects of resveratrol against oxidative injury in the heart, kidney and brain tissues of rats induced with the two‐kidney, one‐clip (2K1C) hypertension model were investigated. Methods Wistar albino rats were divided into sham‐operated (n = 8) or 2K1C groups, in which rats received either resveratrol (10 mg/kg per day, i.p., n = 8), or saline (n = 8) starting at Week 3 after the surgery and continuing for the following 6 weeks. Indirect blood pressure recordings and echocardiographic images were made to evaluate cardiac function. At the end of Week 9 the animals were decapitated and plasma, heart, kidney and brain were taken for biochemical assays, while aortic rings were prepared for vascular reactivity studies. Key findings 2K1C hypertension resulted in increased blood pressure, aortic hypercontractility and reduced left ventricular function, leading to increased lipid peroxidation and myeloperoxidase activity, concomitant with significant reductions in tissue glutathione, superoxide dismutase, Na+/K+‐ATPase and catalase activities in the cardiac, renal and brain tissues, indicating the presence of oxidative tissue damage in peripheral target organs. Elevated plasma levels of lactate dehydrogenase, creatine kinase, as well as reduced plasma levels of antioxidant capacity and nitric oxide further verified the severity of oxidative injury. A 6‐week treatment with resveratrol reversed all the measured parameters, ameliorated hypertension‐induced oxidative injury in the target organs and improved cardiovascular function. Conclusions Resveratrol improved cardiovascular function through the augmentation of endogenous antioxidants and the inhibition of lipid peroxidation by maintaining a balance in oxidant/antioxidant status, which also ameliorated hypertension‐induced oxidative injury in the cardiac, renal and cerebral tissues. 相似文献
3.
目的研究Ouabain及其受体Na+/K+ ATPase α1、α4抗体对正常人精子运动功能的影响。方法将60例正常人的精液上游法进行优化,其中30例与不同浓度Ouabain共孵育,在1,2,3,4 h采用CASA检测精子运动参数;另外30例分别与Na+/K+ ATPase α1和α4抗体共同孵育,1 h后同样方法检测。结果①与阴性对照组比较,优化后的精子与较高剂量Ouabain（1×10 5 ～1×10 2 mol•L 1）共孵育后,活动率显著下降（P＜0.05）,a+b级精子所占比例显著下降（P＜0.01）;但各浓度组两参数差异无显著性;②与阴性对照组比较,较低剂量Ouabain（1×10 6和1×10 7 mol•L 1）作用后,精子活动率和a+b级精子所占比例下降均不明显,两浓度组之间差异无显著性;③Ouabain作用后,精子其他运动参数如直线速度、鞭打频率、直线性、前向性、摆动性均未见显著变化。④Anti α1 和Anti α4作用后的精子活动率均显著下降（均P＜0.01）;但两者之间差异无显著性;⑤Anti α1和Anti α4作用后的a+b级精子所占比例均显著下降（均P＜0.01）;且Anti α4作用后降低的幅度明显大于Anti α1（P＜0.05）;⑥Na+/K+ ATPaseα1和α4抗体作用后,精子其他运动参数如直线速度、鞭打频率、直线性、前向性、摆动性均未见显著变化。结论Ouabain在体外能够降低正常人精子运动功能;Na+/K+ ATPase α1、α4抗体也能够降低精子运动功能,但α4抗体的作用更明显。 相似文献
4.
P-type ATPases constitute a ubiquitous superfamily of cation transport enzymes, responsible for carrying out actions of paramount importance in biology such as ion transport and expulsion of toxic ions from cells. The harmonized toggling of gates in the extra- and intracellular domains explain the phenomenon of specific cation binding in selective physiological states. A quantitative understanding of the fundamental aspects of ion transport mechanism and regulation of P-type ATPases requires detailed knowledge of thermodynamical, structural, and functional properties. Computational studies have made significant contributions to our understanding of biological ion pumps. Various 3D structures of Ca(2+) -ATPase between E1 and E2 transition states have given a impetus to the theorists to work on the Na(+) K(+) - and H(+) K(+) -ATPase to address important questions about their function. The current review delineates the importance of cation, nucleotide, and inhibitor binding domains, with a focus on the therapeutic potential and biological relevance of the three P-type II ATPases. This will give an insight into the ion selectivity and their conduction across the transmembrane helices of P-type II ATPases, which may pave the way to a range of fundamental questions about the mechanism and aid in the efforts of structure- and analog-based drug design. 相似文献
5.
Antonio Dell'Anno Francesca Raffaelli Roberto Danovaro Laura Nanetti Arianna Vignini Cinzia Moroni Laura Mazzanti 《Environmental toxicology》2008,23(1):9-14
Contamination of marine environments by hexachlorobenzene (HCB) represents a serious concern for potential consequences on ecosystem and human health. Despite this, information on cytotoxic effects on marine organisms is still largely lacking. In this study, we investigated cytotoxic effects induced by HCB on gonads and muscular tissue of Squilla mantis by analysing Na(+)/K(+)-ATPase activity and plasma membrane fluidity. This crustacean species was selected as a model for its habitat, trophic level, feeding behavior, and commercial exploitation for human consumption. Time course experiments revealed that low concentrations of HCB (i.e. 50 nM) determine an exponentially decrease of Na(+)/K(+)-ATPase activity and a significant modification of cellular membrane fluidity. Significant negative relationships between Na(+)/K(+)-ATPase activity and membrane fluidity were observed, suggesting that changes in the structure and packing of cellular membranes induced by HCB may be the primary factor affecting the activity of essential bilayer-associated enzymes. Overall these findings suggest that even small concentrations of HCB may determine important changes on cell metabolism with potential cascade effects on recruitment of this commercial species. 相似文献
6.
Evidence shows that Na(+)/K(+)-ATPase from kidney, brain and liver is inhibited by nitric oxide (NO) and peroxynitrite anion (ONO(2) (-)), but the mechanism is unknown. The aim of the present work was to study the inhibitory effect of NO and ONO(2) (-) on erythrocyte Na(+)/K(+)-ATPase. Erythrocyte membranes were isolated from male Wistar rats by hypotonic washing. The membranes (free from haemoglobin) were incubated for Na(+)/K(+)-ATPase activity measurement at various concentrations of ATP in the presence or absence of 400 microM SNAP (an NO donor) or 100 microM SIN-1 (an ONO(2)(-) donor). At these concentrations, SNAP and SIN-1 released about the same amount (100 microM) of NO or ONO(2)(-), respectively, as monitored by measuring NO(2)(-) + NO(3)(-). Both SNAP and SIN-1 decreased V(max) by ca. 75% but they did not decrease the apparent affinity of the Na(+)/K(+)-ATPase for the substrate (a decrease of K(m) was even observed after SNAP treatment). The pattern of this inhibition is compatible either with oxidation of SH groups directly involved in ATP binding but in a way that is not surmountable by increasing the substrate concentration ("non-competitive") or with oxidation of SH groups located outside the active site of the enzyme but important for the activity of the enzyme. 相似文献
7.
Cameron T. Durlacher Kevin Chow Xiao‐Wu Chen Zhi‐Xu He Xueji Zhang Tianxin Yang Shu‐Feng Zhou 《Clinical and experimental pharmacology & physiology》2015,42(5):427-443
The Na+/K+‐translocating adenosine triphosphatase (ATPase) transports sodium and potassium across the plasma membrane and represents a potential target in cancer chemotherapy. Na+/K+‐ATPase belongs to the P‐type ATPase family (also known as E1–E2 ATPase), which is involved in transporting certain ions, metals, and lipids across the plasma membrane of mammalian cells. In humans, the Na+/K+‐ATPase is a binary complex of an α‐subunit that has four isoforms (α1–α4) and a β‐subunit that has three isoforms (β1–β3). This review aims to update our knowledge on the role of Na+/K+‐ATPase in cancer development and metastasis, as well as on how Na+/K+‐ATPase inhibitors kill tumour cells. The Na+/K+‐ATPase has been found to be associated with cancer initiation, growth, development, and metastasis. Cardiac glycosides have exhibited anticancer effects in cell‐based and mouse studies via inhibition of the Na+/K+‐ATPase and other mechanisms. Na+/K+‐ATPase inhibitors may kill cancer cells via induction of apoptosis and autophagy, radical oxygen species production, and cell cycle arrest. They also modulate multiple signalling pathways that regulate cancer cell survival and death, which contributes to their antiproliferative activities in cancer cells. The clinical evidence supporting the use of Na+/K+‐ATPase inhibitors as anticancer drugs is weak. Several phase I and phase II clinical trials with digoxin, Anvirzel, and huachansu (an intravenous formulated extract of the venom of the wild toad), either alone or more often in combination with other anticancer agents, have shown acceptable safety profiles but limited efficacy in cancer patients. Well‐designed randomized clinical trials with reasonable sample sizes are certainly warranted to confirm the efficacy and safety of cardiac glycosides for the treatment of cancer. 相似文献
8.
Qiong Yuan Qian‐Yi Zhou Du Liu Lun Yu Lin Zhan Xiao‐Jing Li Hong‐Yan Peng Xiu‐Ling Zhang Xin‐Chu Yuan 《Clinical and experimental pharmacology & physiology》2014,41(2):127-133
- Decreased Na+/K+‐ATPase activity, and both sirtuin 1 (SIRT1) and adenosine monophosphate‐activated protein kinase (AMPK) have been reported to be involved in the development of diabetic cardiomyopathy (DCM).
- The present study aimed to investigate the advanced glycation end‐products (AGE) that impair Na+/K+‐ATPase stability by regulating the AMPK/SIRT1 pathway during progression of DCM.
- To study type 1 diabetic mellitus (T1DM), a disease model in rats was established by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg), and neonatal rat cardiomyocytes were also cultured. Heart function was detected by Doppler, and SIRT1 and AMPK protein expression were detected by immunohistochemistry and western blotting. Na+/K+‐ATPase activity was also monitored.
- Using in vivo rat models of DCM, we showed that Na+/K+‐ATPase activity decreased when both AMPK and SIRT1 expression were downregulated. In vitro, AGE impaired Na+/K+‐ATPase activity and decreased the AMPK and SIRT1 expression.
- Sirtuin 1 overexpression increased Na+/K+‐ATPase activity. 5‐aminoimidazole‐4‐carboxamide‐3‐ribonucleoside (AICAR) upregulated SIRT1 expression and increased Na+/K+‐ATPase activity, which could be partially abolished by splitomicin.
- Our results suggest that the dysfunction of DCM is related to AGE‐induced Na+/K+‐ATPase activity impairment through a mechanism involving the AMPK/SIRT1 pathway.
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10.
Tayrine Paschoaletti Benze Marise Margareth Sakuragui Lucas Henrique de Paula Zago Marisa Narciso Fernandes 《Environmental toxicology》2016,31(5):533-542
The action of diflubenzuron (DFB) was evaluated in a freshwater fish, Prochilodus lineatus, after exposure to 0.06, 0.12, 0.25, or 0.50 mg L?1 DFB for 14 days. Erythrocyte nuclear abnormalities (ENA), the gill activity of Na+/K+‐ATPase, H+‐ATPase and carbonic anhydrase (CA), and lipid peroxidation (LPO) and histopathological changes in the gills and liver were determined. The number of micronuclei increased in fish exposed to 0.25 and 0.50 mg L?1 DFB. Plasma Cl? and the CA activity decreased, while the activity of Na+/K+‐ATPase and of H+‐ATPase increased in fish exposed to 0.25 and 0.50 mg L?1 DFB. LPO did not change in the gills but increased in the liver of fish exposed to 0.25 and 0.50 mg L?1 DFB. In the gills, histopathological changes indicated disperse lesions and slight to moderate damage in fish exposed to 0.50 mg L?1 DFB, whereas in the liver, these changes were significantly greater in fish exposed to 0.25 and 0.50 mg L?1 DFB, indicating moderate to severe damage. Continuous exposure to DFB is potentially toxic to P. lineatus, causing heath disorders when the fish is exposed to the two highest DFB concentrations, which are applied to control parasites in aquaculture and to control mosquito populations in the environment. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 533–542, 2016. 相似文献
11.
A previous study revealed that a single i.p. administration of 6 mg/kg body wt. of mercuric chloride (MC) durably inhibits the rat cerebral microvascular Na+/K+-ATPase activity [1]. In this study, cerebral microvessels isolated 18 h after MC treatment were compared to those obtained from control rats and subsequently treated or not treated with MC in vitro, with regard to: (a) 3H]ouabain binding to, and (b) K+-activation kinetics of, the Na+/K+-ATPase. Microvessels from MC-treated rats showed a decrease of 3H]ouabain binding down to 62% of the control binding, and the same degree of inhibition was attained in microvessels treated in vitro with 5 μM MC. Analysis of the K+-activation kinetics of Na+/K+-ATPase revealed a decrease of Vmax from the control value of 13.1 to 7.67 μmol/mg/h in microvessels from MC-treated rats and 6.07 μmol/mg/h in microvessels treated in vitro with 5 μM MC, with no change in Km in either case. The similarity of the effects of in vivo and in vitro treatments suggests that the inhibition of the cerebromicrovascular Na+/K+ATPase following in vivo administration of MC results from a direct interaction of Hg+ with the enzyme. 相似文献
12.
目的检测哇巴因对正常大鼠和阿霉素所致心衰大鼠左心室肌细胞的收缩力、钙瞬变和舒张期钙影响。方法腹腔注射阿霉素制备大鼠心衰模型,以改良的Langendorff装置分离心肌细胞,负载Fluo-4钙荧光染料后采用IonOptix可视化细胞动缘探测系统检测哇巴因对大鼠心肌细胞收缩功能、舒张期钙及钙瞬变的变化。结果哇巴因可浓度依赖性增加正常大鼠心肌细胞收缩力和钙瞬变,3×10-7 mol·L-1哇巴因即明显增加收缩力和钙瞬变,但对心衰大鼠心肌细胞,1×10-5 mol·L-1哇巴因才明显增加心肌细胞收缩力和钙瞬变;哇巴因也可增加正常大鼠和心衰大鼠心肌细胞舒张期钙。结论哇巴因能够增加心肌细胞收缩力、钙瞬变和舒张期钙,阿霉素所致心衰大鼠心肌细胞较正常细胞不敏感。 相似文献
13.
The aim of this study was to investigate the effects caused by subchronic exposure to diphenyl diselenide in rats. Adult Wistar rats were exposed to diphenyl diselenide (5-300 micromol kg(-1), subcutaneously) once a day for 14 days. The subchronic administration of diphenyl diselenide at a dose of 300 micromol kg(-1) significantly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Conversely, this exposure did not alter lactate dehydrogenase (LDH) activity, urea and creatinine levels in plasma. The activity of delta-aminolevulinate dehydratase (delta-ALA-D) from liver and kidney was inhibited by high dosages of diphenyl diselenide. Diphenyl diselenide did not alter renal Na(+)/K(+)ATPase. A decline in body weight gain was associated with a decrease in food consumption in rats treated with 100 or 300 micromol kg(-1) diphenyl diselenide. At these dosages (100 and 300 micromol kg(-1)), diphenyl diselenide did not cause histological alterations in the liver of rats. Taken together, these results demonstrated that subchronic exposure to diphenyl diselenide at high doses induced minor toxicological effects. 相似文献
14.
Xuefeng Ren Xin Wu Gang Sui Zhihong Gong Emmanuel Yawson Banghua Wu Guanchao Lai Xiaolin Ruan Hongbin Gao Feng Zhou Bing Su James R. Olson Xiaojiang Tang 《Journal of applied toxicology : JAT》2015,35(5):500-507
We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180‐day animal study and exposed the randomly grouped Sprague–Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg–1 day–1. Transient behavioral changes were observed in the high‐dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose‐dependent inhibition of renal H+/K+‐ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg–1 day–1 dose group and 3 out of 9 rats in the 131.3 µg kg–1 day–1 dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X‐ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium‐containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
15.
JF Briffa E Grinfeld KA Jenkin ML Mathai P Poronnik AJ McAinch DH Hryciw 《Clinical and experimental pharmacology & physiology》2015,42(10):1118-1126
The consumption of a high fat diet (HFD) is associated with proteinuria and altered sodium handling and excretion, which can lead to kidney disease. In the proximal tubule, the Na+/H+ Exchanger 3 (NHE3) is responsible for normal protein reabsorption and the reabsorption of approximately 70% of the renal sodium load. It is the Na+/K+‐ATPase that provides the driving force for the reabsorption of sodium and its exit across the basolateral membrane. This study investigates the effects that consumption of a HFD for 12 weeks has on NHE3 and Na+/K+‐ATPase expression in the kidney. Western blot analysis identified a significant reduction in NHE3 and its modulator, phosphorylated protein kinase B, in renal lysate from obese rats. In the obese rats, a reduction in NHE3 expression in the proximal tubule may impact on the acidification of endosomes which are responsible for albumin uptake, suggesting a key role for the exchanger in protein endocytosis in obesity. Western blot analysis identified a reduction in Na+/K+‐ATPase which could also potentially impact on albumin uptake and sodium reabsorption. This study demonstrates that consumption of a HFD for 12 weeks reduces renal NHE3 and Na+/K+‐ATPase expression, an effect that may contribute to the albuminuria associated with obesity. Furthermore the reduction in these transporters is not likely to contribute to the reduced sodium excretion in obesity. These data highlight a potential link between NHE3 and Na+/K+‐ATPase in the pathophysiological changes in renal protein handling observed in obesity. 相似文献
16.
《Expert opinion on therapeutic patents》2013,23(5):825-859
This review focuses on ion-transporting ATPases which play an essential role in the generation and maintenance of ionic gradients between cell compartments and environment. There are three types of cation transporting ATPases: oligomycin sensitive F-ATPases, bafilomycin-sensitive V (vacuolar) H+-transporting ATPases (V-ATPases) and vanadate-sensitive P (phosphate binding) ATPases (P-ATPases), the most important of these being Ca2+-ATPase, Na+/K+-ATPase and H+/K+-ATPase. The influences of numerous modulators are reviewed. 相似文献
17.
目的 观察异丙酚 (propofol)麻醉不同时期大鼠大脑皮层、海马和脑干Na+ ,K+ ATPase、Ca2 + ATPase活性的动态变化 ,探讨异丙酚的全麻作用机制。方法 ♀SD大鼠 40只 ,按麻醉不同时期随机分为 5组。分别在腹腔注射 (ip) 10ml·kg-1生理盐水 2min后 (对照组 ) ,ip异丙酚 10 0mg·kg-12min后、翻正反射消失前 (诱导期组 ) ,翻正反射消失后 3 0min(麻醉期组 ) ,翻正反射刚恢复、尚未完全清醒时 (恢复期组 ) ,动物完全清醒后 (清醒期组 ) ,断头取脑。用分光光度法测定各脑区Na+ ,K+ ATP酶和Ca2 + ATP酶的活性。结果 与对照组比较 ,异丙酚 10 0mg·kg-1使大脑皮层、海马和脑干的Na+ ,K+ ATP酶和Ca2 + ATP酶的活性在诱导期即降低 ,麻醉期进一步降低 (P <0 0 5 ,P <0 0 1) ,恢复期开始升高 ,但仍低于对照组 ,清醒期基本恢复到对照组水平。结论 异丙酚 10 0mg·kg-1能明显抑制脑ATP酶活性且与行为变化平行 ,提示ATP酶可能在异丙酚的全麻机制中发挥重要作用 相似文献
18.
It has been suggested that vanadium, a potent reversible inhibitor of sodium-potassium-sensitive adenosine triphosphatase (Na+/K+-ATPase), is of aetiological importance in manic-depressive illness. The present review submits to critical scrutiny the pertinent literature of (1) the existence of vanadium excess in various tissues; (2) Na+/K+-ATPase activity in erythrocytes from patients with affective illness; and (3) treatment modalities applied to reduce body vanadium or to increase ‘sodium’ activity. Finally, data on vanadium deficiency as well as vanadium poisoning are discussed. 相似文献
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20.
The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na(+)-K(+) ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na(+)-K(+) ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg(++). The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na(+)-K(+) ATPase inhibition. The role of membrane Na(+)-K(+) ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na(+)-K(+) ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. 相似文献
