CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

Hemiplegia ; diagnosis ; genetics ; Humans ; Mutation ; Prognosis ; Sodium-Potassium-Exchanging ATPase ; genetics

Epilepsy ; etiology ; Hemiplegia ; complications ; genetics ; Humans ; Infant ; Male ; Mutation ; Sodium-Potassium-Exchanging ATPase ; genetics

Abnormal cholesterol metabolism is associated with an elevated risk of developing atherosclerosis, hypertension, and diabetes etc. Na(+)/K(+)-ATPase was found to regulate cholesterol synthesis, distribution and trafficking. This study aimed to examine the effect of high-fat diet on cholesterol metabolism in rats and the role of Na(+)/K(+)-ATPase/Src/ERK signaling pathway in the process. Forty male SD rats were evenly divided into high-fat diet group and control group at random. Animals in the former group were fed on high-fat diet for 12 weeks, and those fed on basic diet served as control. Blood lipids, including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesteral (LDL-C) levels, were detected at 3, 6 and 12 weeks. The ratio of cholesterol content in cytoplasm to that in cell membrane was detected in liver tissues. RT-PCR and Western blotting were used to measure the expression of lipid metabolism-associated genes (HMG-CoA reductase and SREBP-2) after 12-week high-fat diet. Na(+)/K(+)-ATPase/Src/ERK signaling pathway-related components (Na(+)/K(+)-ATPase α1, Src-PY418 and pERK1/2) were also measured by Western blotting. The results showed that the serum TC, TG, and LDL-C levels were significantly higher in high-fat diet group than those in control group, while the HDL-C level was significantly lower in high-fat diet group at 6 weeks (P<0.01). High-fat diet led to an increase in the cholesterol content in the cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to that in cell membrane was elevated over time. The expression of HMG-CoA reductase and SREBP-2 was significantly suppressed at mRNA and protein levels after 12-week high-fat diet (P<0.05). Moreover, high-fat diet promoted the expression of Na(+)/K(+)-ATPase α1 but suppressed the phosphorylation of Src-PY418 and ERK1/2 at 12 weeks (P<0.05). It was concluded that high-fat diet regulates cholesterol metabolism, and Na(+)/K(+)-ATPase signaling pathway is involved in the process possibly by regulating the expression of lipid metabolism-associated proteins HMG-CoA reductase and SREBP-2.
Acyl Coenzyme A ; genetics ; metabolism ; Animals ; Cell Membrane ; metabolism ; Cholesterol ; blood ; Cytoplasm ; metabolism ; Diet, High-Fat ; adverse effects ; Gene Expression Regulation ; drug effects ; Lipid Metabolism ; drug effects ; Liver ; metabolism ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; genetics ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; genetics ; metabolism

Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg · kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg · kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism.
Animals ; Energy Metabolism ; drug effects ; Glucosides ; pharmacology ; Heme Oxygenase-1 ; genetics ; Lipopolysaccharides ; pharmacology ; Male ; Membrane Proteins ; genetics ; Mice ; Mice, Inbred BALB C ; Monoterpenes ; pharmacology ; Oxidative Stress ; drug effects ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo analyze the ATP1A3 mutations in patients with alternating hemiplegia of childhood (AHC) and recognize its value in diagnosing atypical cases.

METHODData of all AHC patients seen at Peking University First Hospital from August 2005 to November 2014 were prospectively collected. Clinical information of the AHC patients and their family members were collected and analyzed. Genomic DNAs were extracted from their peripheral blood. Mutations in ATP1A3 were screened by Sanger sequencing after PCR.

RESULTA total of 78 AHC patients were recruited, including 50 males and 28 females. Only three patients had family history of AHC. The first family case had affected mother with AHC; the second family case was the older one of a monozygotic male twins with AHC but their parents were normal; the third family case had a sister with AHC but their parents were normal. The age of onset ranged from six hours to eight years and six months (median: 4 months). According to the Aicardi's clinical diagnostic criteria, 72 patients were considered as typical AHC cases and the other six patients were considered as atypical AHC cases for their age of onset was older than 18 months. Twenty-seven different missense ATP1A3 mutations were detected in 71 (91.0%, 71/78) patients with AHC, including 66 typical and 5 atypical cases. 11 novel ATP1A3 mutations were first reported. ATP1A3 mutations were identified in the three AHC cases with family history. Parental analysis verified that the ATP1A3 mutation of 63 patients (95.5%, 63/66) were de novo origin except lack of five unavailable maternal or paternal genomic DNA. Mutation D801N was found in 20 cases (28.2%), and E815K in 12 cases (16.9%). In the six atypical AHC patients, ATP1A3 mutations were detected in five of them.

CONCLUSIONATP1A3 was the major causative gene of AHC, and mutations were identified as de novo mostly. ATP1A3 mutations in AHC had mutational hotspot, and the most common mutations were D801N and E815K. ATP1A3 mutation screening is helpful for the genetic and definite diagnosis of the atypical AHC cases.

Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Hemiplegia ; genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation, Missense ; Sodium-Potassium-Exchanging ATPase ; genetics

OBJECTIVETo study the effect of Tongluo Xingnao effervescent tablets on learning and memory capacity and expression of Na(+)-K(+)-ATPase in hippocampus of rats with chronic cerebral ischemia-induced learning and memory dysfunction model.

METHODThe 2-VO method was used to establish sd rat model learning and memory dysfunction induced by chronic cerebral ischemia. The 50 rats in the successfully established model were randomly divided into the model control group, the Dihydroergotoxine Mesylate tablets group (0.7 mg x kg(-1), Tongluo Xingnao effervescent tablets high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups and the sham operation group (n = 10) as the control group. The groups were orally given 10 ml x kg(-1) x d(-1) drugs for consecutively 90 days. On the 86th day, Morris water maze was adopted for them. On the 90th day, a leaning and memory capacity test was held. The brain tissues were fixed with 10% formaldehyde and observed for pathomorphism after routine slide preparation and staining. The expression of hippocampal Na(+)-K(+)-ATPase was detected with immunohistochemistry and image quantitative analysis.

RESULTCompared with the model group, all of Tongluo Xingnao effervescent tablets groups showed significant decrease in the escape latency at the 5th day in the Morris water maze, and notable increase in the frequency of the first quadrant dwell, the frequency passing the escape platform and the frequency entering effective area (p < 0.05). According to the pathomorphological detection, the control group showed a significantly higher pathological score than the sham operation group (p < 0.01), the middle dose group showed a significantly lower pathological score than the model group (p < 0.05). According to the immunohistochemistical detection, the model control group showed a remarkably lower mean OD value of Na(+)-K(+)-ATPase than the sham operation group (p < 0.05), high and middle dose groups showed a significantly higher mean od value than the model control group (p < 0.01).

CONCLUSIONTongluo Xingnao effervescent tablets can improve the learning and memory capacity, reduce pathological changes of hippocampal tissues of rats with chronic cerebral ischemia-induced learning and memory dysfunction model, and promote the expression of Na(+)-K(+)-ATPase in hippocampus.

Animals ; Brain Ischemia ; drug therapy ; enzymology ; genetics ; psychology ; Chronic Disease ; drug therapy ; psychology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hippocampus ; drug effects ; enzymology ; Humans ; Learning ; drug effects ; Male ; Memory ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; genetics ; metabolism ; Tablets ; administration & dosage

OBJECTIVETo investigate the common rule of hepatic energy metabolism on rats by six traditional Chinese medicine (TCM) with hot property.

METHODThe activity of Na(+)-K(+)-ATPase, Ca2(+)-ATPase and succinate hydrogenase (SDH), the content of hepatic glycogen and the mRNA expression of hepatic uncoupling protein2 (UCP2) were measured after the rats were administrated with water extracts of Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis, Rhizoma Alpiniae Officinarum, Pericarpium Zanthoxyli and Cortex Cinnamomi, Fructus Evodiae at the dose of 10.5, 8.4, 6.0, 4.0, 3.5, 4.2 g x kg(-1). respectively in 30 days, twice a day.

RESULTThe activity of Na+(-)K(+)-ATPase has been increased by the six TCM and the statistical significance has been observed in Rhizoma Alpiniae Officinarum, Pericarpium Zanthoxyli, Fructus Evodiae groups. The raising tendency of Ca2(+)-ATPase activity has been observed by the six TCM and the statistical significance has been obtained in Rhizoma Alpiniae Officinarum group. The activity of SDH has been increaseded by six TCM while statistical significance has been observed except in five groups of the six groups except in Radix Aconiti Lateralis Preparata group. The content of hepatic glycogen has been decreased significantly by six TCM. No signiticant change of the mRNA expression of UCP2 has been found.

CONCLUSIONTCM has good effects on hepatic energy metabolism by raising the activity of mitochondria SDH to increase the production of ATP and by increasing the activity of Na(+)-K+)-ATPase, Ca2(+)-ATPase to increase the consumption of ATP.

Animals ; Calcium-Transporting ATPases ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Energy Metabolism ; drug effects ; Gene Expression ; drug effects ; Ion Channels ; genetics ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; Male ; Mitochondrial Proteins ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; genetics ; metabolism ; Succinate Dehydrogenase ; genetics ; metabolism ; Uncoupling Protein 2

OBJECTIVETo investigate the association of the polymorphisms of rs4961 in alpha-adducin (ADD1) and rs28933400 in Na+/K+ -ATPase a2 (ATP1A2) genes, the products of which are important for sodium transport, with essential hypertension.

METHODSMutagenically separated PCR (MS-PCR) was used to detect the genotypes of the two loci. The subjects were recruited randomly including 196 patients of essential hypertension and 192 healthy controls.

RESULTSThe frequencies of genotypes and alleles of in the ADD1 gene were significantly different between the patients and controls respectively (P=0.03, P=0.04). There was significant relationship between the genotypes of rs4961 and systolic blood pressure and blood sodium concentration. However, there was no significant relationship between the rs4961 genotypes and diastolic blood pressure, body mass index, blood kalium and chlorine concentrations. There was no polymorphism at the rs28933400 locus in the subjects analyzed.

CONCLUSIONThe rs4961 polymorphism of the ADD1 gene is associated with essential hypertension, but the rs28933400 locus in the ATP1A2 gene may have no association with essential hypertension in the studied population.

Calmodulin-Binding Proteins ; genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; genetics ; pathology ; physiopathology ; Ion Transport ; Male ; Middle Aged ; Polymorphism, Genetic ; Sodium ; metabolism ; Sodium-Potassium-Exchanging ATPase ; genetics

OBJECTIVETo assess the binding activity of polypeptide containing human Na+, K+-ATPase alpha1 subunit M1-M2 extracellular segment (HES1 derivative).

METHODSHES1 derivative was synthesized by Fmoc method and purified by high-performance liquid chromatography-mass spectrometry, and its binding activity was identified by radioligand binding assay.

RESULTS3H-ouabain and synthetic HES1 derivative showed some binding activity with the equilibrium dissociation constant (KD) of 24.58 nmol/L, with the the receptor density of 492.43 fmol x mg(-1) pro. and IC50 of 3.078 x 10(-7) mol/L.

CONCLUSIONHES1 derivative can bind to ouabain and has the potential of becoming an effective therapeutic agent.

Binding Sites ; drug effects ; Extracellular Space ; metabolism ; Humans ; Ouabain ; chemistry ; pharmacology ; Peptides ; chemistry ; Protein Binding ; Sodium-Potassium-Exchanging ATPase ; chemistry ; genetics ; metabolism