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1.
Article in English | WPRIM | ID: wpr-878413

ABSTRACT

OBJECTIVES@#A study was conducted to investigate the molecular mechanism of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) influencing the invasion and metastasis of tongue squamous cell carcinoma and to provide a new target for clinical inhibition of invasion and metastasis of tongue squamous cell carcinoma.@*METHODS@#Ualcan website was used to analyze the expression of CHD1L in normal epithelial tissue and primary head and neck squamous cell carcinoma and to analyze the effect of lymph node metastasis on the expression of CHD1L in tissues with head and neck squamous cell carcinoma. The relationship between CHD1L expression and the survival rate of patients with head and neck squamous cell carcinoma was tested by the GEPIA website. Western blot was used to quantify the levels of CHD1L protein in human tongue squamous cell carcinoma CAL27 and immortalized human skin keratinocyte cell HaCaT. After knocking down CAL27 in human tongue squamous cell carcinoma cells with an RNA interference plasmid, the cells were designated as SiCHD1L/CAL27 and Scr/CAL27. Western blot was utilized to detect the expression of CHD1L in each group of cells. The change in CAL27 cell proliferation ability was tested by EdU proliferation test after CHD1L knockdown. The change of cell migration ability of each group cells was tested through the wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) marker E-cadherin and Vimentin protein expression levels.@*RESULTS@#Ualcan database showed that the expression of CHD1L in primary head and neck squamous cell carcinoma tissues was higher than in normal epithelial tissues and in head and neck squamous cell carcinoma tissues with lymph node metastasis. GEPIA website analysis showed that the overall survival rate of patients with head and neck squamous cell carcinoma with high expression of CHD1L was significantly lower than that of patients with low expression. Western blot results showed that CHD1L expression in human tongue squamous carcinoma cells CAL27 was higher than that of human normal skin cells HaCaT. CHD1L expression in SiCHD1L/CAL27 cells was much lower than that in Scr/CAL27 cells. Results of EdU proliferation experiments showed the significant reduction in the cell proliferation ability of the SiCHD1L/CAL27 cells. Results of the wound healing experiments showed the reduction in the migration capacity of the SiCHD1L/CAL27 cells. The expression of E-cadherin increased, whereas that of Vimentin decreased, in SiCHD1L/CAL27 cells.@*CONCLUSIONS@#CHD1L promoted the EMT, proliferation, migration, and invasion ability of tongue squamous cell carcinoma cells.


Subject(s)
Adenosine Triphosphatases , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , DNA Helicases , DNA-Binding Proteins , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Humans , Neoplasm Invasiveness/genetics , Tongue , Tongue Neoplasms/genetics
2.
Mem. Inst. Oswaldo Cruz ; 115: e190457, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1135252

ABSTRACT

BACKGROUND Imitation SWItch (ISWI) ATPase is the catalytic subunit in diverse chromatin remodeling complexes. These complexes modify histone-DNA interactions and therefore play a pivotal role in different DNA-dependent processes. In Trypanosoma cruzi, a protozoan that controls gene expression principally post-transcriptionally, the transcriptional regulation mechanisms mediated by chromatin remodeling are poorly understood. OBJECTIVE To characterise the ISWI remodeler in T. cruzi (TcISWI). METHODS A new version of pTcGW vectors was constructed to express green fluorescent protein (GFP)-tagged TcISWI. CRISPR-Cas9 system was used to obtain parasites with inactivated TcISWI gene and we determined TcISWI partners by cryomilling-affinity purification-mass spectrometry (MS) assay as an approximation to start to unravel the function of this protein. FINDINGS Our approach identified known ISWI partners [nucleoplasmin-like protein (NLP), regulator of chromosome condensation 1-like protein (RCCP) and phenylalanine/tyrosine-rich protein (FYRP)], previously characterised in T. brucei, and new components in TcISWI complex [DRBD2, DHH1 and proteins containing a domain characteristic of structural maintenance of chromosomes (SMC) proteins]. Data are available via ProteomeXchange with identifier PXD017869. MAIN CONCLUSIONS In addition to its participation in transcriptional silencing, as it was reported in T. brucei, the data generated here provide a framework that suggests a role for TcISWI chromatin remodeler in different nuclear processes in T. cruzi, including mRNA nuclear export control and chromatin compaction. Further work is necessary to clarify the TcISWI functional diversity that arises from this protein interaction study.


Subject(s)
Animals , Transcription Factors/genetics , Trypanosoma cruzi/genetics , Adenosine Triphosphatases/genetics , Chromatin Assembly and Disassembly/genetics , Gene Expression Regulation , Blotting, Western , Flow Cytometry
3.
Article in Chinese | WPRIM | ID: wpr-781710

ABSTRACT

Floating-Harbor syndrome (FHS) is an autosomal dominant genetic disease caused by SRCAP mutation. This article reports the clinical features of a boy with FHS. The boy, aged 11 years and 7 months, attended the hospital due to short stature for more than 8 years and had the clinical manifestations of unusual facial features (triangularly shaped face, thin lips and long eyelashes), skeletal dysplasia (curvature finger), expressive language disorder, and retardation of bone age. Genetic detection revealed a novel heterozygous mutation, c.7330 C>T(p.R2444X), in the SRCAP gene. The boy was diagnosed with FHS based on these clinical manifestations and gene detection results. FHS is rare in clinical practice, which may lead to missed diagnosis and misdiagnosis, and gene detection may help with the clinical diagnosis of FHS in children.


Subject(s)
Abnormalities, Multiple , Adenosine Triphosphatases , Child , Craniofacial Abnormalities , Growth Disorders , Heart Septal Defects, Ventricular , Humans , Male
4.
Article in Chinese | WPRIM | ID: wpr-771507

ABSTRACT

The aim of this paper was to investigate the inhibitory effect of extract of Coptidis Rhizoma(ECR) on invasion of Candida albicans hyphae in vitro.XTT reduction method was used to evaluate the metabolic activity of C.albicans.The colony edge growth of C.albicans was observed by solid medium.The growth of C.albicans hyphae was determined on semi-solid medium.The morphology and viability changes of C.albicans hyphae were assessed by scanning electron microscope and fluorescence microscope.qRT-PCR method was used to detect the ALS3 and SSA1 expression of C.albicans invasin genes.The results showed that the metabolic viability by XTT method detected that the activity of C.albicans was gradually decreased under the intervention of 64,128 and 256 mg·L-1 of ECR respectively.128,256 mg·L-1 of ECR significantly inhibited colony folds and wrinkles on solid medium and the hyphal invasion in semi-solid medium.Scanning electron microscopy and fluorescence microscopy showed that 128,256 mg·L-1 of ECR could inhibit the formation of C.albicans hyphae.qRT-PCR results showed that the expression of invasin gene ALS3 and SSA1 was down-regulated,and especially 256 mg·L-1 of ECR could down-regulate the two genes expression by 4.8,1.68 times respectively.This study showed that ECR can affect the invasiveness of C.albicans by inhibiting the growth of hyphae and the expression of invasin.


Subject(s)
Adenosine Triphosphatases , Genetics , Candida albicans , Drugs, Chinese Herbal , Pharmacology , Fungal Proteins , Genetics , Gene Expression Regulation, Fungal , HSP70 Heat-Shock Proteins , Genetics , Hyphae , Microscopy, Electron, Scanning
5.
Biol. Res ; 52: 6, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011409

ABSTRACT

BACKGROUND: Pollen development is an energy-consuming process that particularly occurs during meiosis. Low levels of adenosine triphosphate (ATP) may cause cell death, resulting in CMS (cytoplasmic male sterility). DNA sequence differences in ATP synthase genes have been revealed between the N- and S-cytoplasms in the cotton CMS system. However, very few data are available at the RNA level. In this study, we compared five ATP synthase genes in the H276A, H276B and fertile F1 (H276A/H268) lines using RNA editing, RNA blotting and quantitative real time-PCR (qRT-PCR) to explore their contribution to CMS. A molecular marker for identifying male sterile cytoplasm (MSC) was also developed. RESULTS: RNA blotting revealed the absence of any novel orf for the ATP synthase gene sequence in the three lines. Forty-one RNA editing sites were identified in the coding sequences. RNA editing showed that proteins had 32.43% higher hydrophobicity and that 39.02% of RNA editing sites had proline converted to leucine. Two new stop codons were detected in atp6 and atp9 by RNA editing. Real-time qRT-PCR data showed that the atp1, atp6, atp8, and atp9 genes had substantially lower expression levels in H276A compared with those in H276B. By contrast, the expression levels of all five genes were increased in F1 (H276A/H268). Moreover, a molecular marker based on a 6-bp deletion upstream of atp8 in H276A was developed to identify male sterile cytoplasm (MSC) in cotton. CONCLUSIONS: Our data substantially contributes to the understanding of the function of ATP synthase genes in cotton CMS. Therefore, we suggest that ATP synthase genes might be an indirect cause of cotton CMS. Further research is needed to investigate the relationship among ATP synthase genes in cotton CMS.


Subject(s)
Cell Membrane/genetics , RNA Editing , Adenosine Triphosphatases/genetics , Gossypium/enzymology , Plant Infertility/genetics , DNA, Mitochondrial/genetics , Polymerase Chain Reaction , Gene Expression Regulation, Plant/genetics , Gossypium/genetics , Cytoplasm/metabolism , RNA, Mitochondrial/genetics
6.
Article in English | WPRIM | ID: wpr-728030

ABSTRACT

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, Wnt/β-catenin and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.


Subject(s)
Adenosine Triphosphatases , Chronic Pain , Cyclic Nucleotide-Gated Cation Channels , Drug Discovery , Endoplasmic Reticulum Stress , Ephrins , Histone Deacetylases , Humans , Models, Animal , Nervous System , Neuralgia , Oxidoreductases , Receptors, Eph Family , Receptors, sigma
7.
Article in Chinese | WPRIM | ID: wpr-813296

ABSTRACT

The subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysms (IAs) is always a lethality. Increasing evidence suggests a familiar aggregation of IA occurrence, which may relate to genetics and there might be an increasing number of IAs in IA families when mutation of disease genes is aggregating. With the progress in the study of familiar intracranial aneurysms (FIAs), a large number of chromosome fragments are found to be related with IAs, such as 1p36, 5q31, 7q11, 14q22, 17cen, 19q13, Xp22. Further studies indicated that mutation of several genes could be the cause of FIAs, including TNFRSF13B, ANRIL, SOX17, ADAMTS15, RNF213 and LOXL2. The independent genetic epidemiologic study on aneurysm families can be used to discover the related genes more effectively, and to explore the mechanism of occurrence of IAs. It's also the precondition for the prevention of disease.


Subject(s)
Adenosine Triphosphatases , Amino Acid Oxidoreductases , Genetic Research , Humans , Intracranial Aneurysm , Genetics , Risk Factors , Ubiquitin-Protein Ligases
8.
Article in Chinese | WPRIM | ID: wpr-773806

ABSTRACT

OBJECTIVE@#To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice.@*METHODS@#Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured.@*RESULTS@#Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(<0.05),the activity of LDH in the serum was obviously improved in the group of the swimming control and SI, and the activity of CK and SDH were both significantly improved in the group of the swimming control and SI except the activity of SDH in the liver of the group SI; compared with the swimming control,the serum contents of Lac,the activities of LDH, ATPase, SDH, CK were obviously improved(<0.05).@*CONCLUSIONS@#Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.


Subject(s)
Adenosine Triphosphatases , Blood , Animals , Creatine Kinase , Blood , Energy Metabolism , Isoflavones , Pharmacology , L-Lactate Dehydrogenase , Blood , Lactic Acid , Blood , Male , Mice , Random Allocation , Soybeans , Chemistry , Succinate Dehydrogenase , Blood , Swimming
9.
Mycobiology ; : 172-176, 2018.
Article in English | WPRIM | ID: wpr-729782

ABSTRACT

A new species belonging to the genus Alternaria was isolated from the necrotic leaf spots of Brassica rapa subsp. pekinensis in Yuseong district, Daejeon, Korea. It is an occasional isolate, not an etiological agent, which is morphologically similar to A. broccoli-italicae, but differs in conidial size and conidiophore shape. Phylogenetic analysis using the sequence datasets of the internal transcribed spacer (ITS) region of the rDNA, glyceraldehyde-3-phosphate dehydrogenase (gpd), and plasma membrane ATPase genes showed that it is distantly related to A. broccoli-italicae and closely related to Alternaria species in the section Pseudoalternaria, which belonged to a clade basal to the section Infectoriae. Morphologically, the species is unique because it produces solitary conidia or conidial chains (two units), unlike the four members in the section Pseudoalternaria that produce conidia as short branched chains. It exhibits weak pathogenicity in the host plant. This report includes the description and illustration of A. brassicifolii as a new species.


Subject(s)
Adenosine Triphosphatases , Alternaria , Brassica rapa , Brassica , Brassicaceae , Cell Membrane , Dataset , DNA, Ribosomal , Korea , Oxidoreductases , Plants , Spores, Fungal , Virulence
10.
Article in English | WPRIM | ID: wpr-93424

ABSTRACT

Cyclic ADP-ribose (cADPR) releases Ca²⁺ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca²⁺ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca²⁺ ([Ca²⁺](i)) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca²⁺ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca²⁺ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.


Subject(s)
Action Potentials , Adenosine Diphosphate , Adenosine Triphosphatases , Calcium , Cyclic ADP-Ribose , Cytochalasin B , Endoplasmic Reticulum , Homeostasis , Muscle Cells , Myocytes, Cardiac , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatases , Reticulum , Ryanodine Receptor Calcium Release Channel , Tyrosine
11.
Article in English | WPRIM | ID: wpr-194441

ABSTRACT

Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo. Mechanistically, alectinib increased the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, alectinib stimulated ATPase activity and competed with substrates of ABCB1 or ABCG2 and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling bound to ABCB1 or ABCG2 but neither altered the expression and localization of ABCB1 or ABCG2 nor the phosphorylation levels of AKT and ERK. Alectinib also enhanced the cytotoxicity of DOX and the intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. These findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR.


Subject(s)
Adenosine Triphosphatases , Carcinoma, Non-Small-Cell Lung , Doxorubicin , Drug Resistance, Multiple , Drug Therapy , Humans , In Vitro Techniques , Leukemia , Lymphoma , Parents , Phosphorylation , Phosphotransferases , Rhodamine 123 , United States Food and Drug Administration
12.
Article in English | WPRIM | ID: wpr-167308

ABSTRACT

PURPOSE: This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H⁺ ATPase (V-ATPase) in cervical cancer. MATERIALS AND METHODS: The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively. RESULTS: Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05). CONCLUSION: V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.


Subject(s)
Adenocarcinoma , Adenosine Triphosphatases , Antineoplastic Agents , Apoptosis , Caspase 3 , Cell Line , Cell Proliferation , Disease-Free Survival , Enzyme-Linked Immunosorbent Assay , Esomeprazole , Humans , Immunohistochemistry , Paclitaxel , Prognosis , Proton Pump Inhibitors , Proton Pumps , Protons , Risk Factors , RNA, Small Interfering , Transfection , Uterine Cervical Neoplasms , Vacuolar Proton-Translocating ATPases
13.
Article in Chinese | WPRIM | ID: wpr-335151

ABSTRACT

<p><b>OBJECTIVE</b>To delineate the clinical features and potential mutation of the ATP7A gene in a family affected with Menkes disease.</p><p><b>METHODS</b>Clinical data of a patient and his family members were analyzed. Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assays were performed to detect the mutation of the ATP7A gene.</p><p><b>RESULTS</b>The patient was admitted at the age of 5 months due to severe epilepsy and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were noted. Cranial magnetic resonance imaging and angiography revealed cortical atrophy, leukoencephalopathy and circuitous of intracranial vessels. The plasma ceruloplasmin was decreased. MLPA has identified a deletion spanning exons 8 to 12 of the ATP7A gene. His mother was found to be a heterozygous carrier of the same mutation.</p><p><b>CONCLUSION</b>The clinical features and a novel mutation of the ATP7A gene of the family have been delineated.</p>


Subject(s)
Adenosine Triphosphatases , Genetics , Adult , Asian Continental Ancestry Group , Genetics , Cation Transport Proteins , Genetics , China , Copper-Transporting ATPases , DNA Mutational Analysis , Exons , Female , Heterozygote , Humans , Infant , Male , Menkes Kinky Hair Syndrome , Genetics , Mutation , Pedigree
14.
Article in Chinese | WPRIM | ID: wpr-297244

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD).</p><p><b>METHODS</b>A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA.</p><p><b>RESULTS</b>Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05).</p><p><b>CONCLUSIONS</b>Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.</p>


Subject(s)
Adenosine Triphosphatases , Metabolism , Adenylyl Cyclases , Physiology , Animals , Attention Deficit Disorder with Hyperactivity , Drug Therapy , Cyclic AMP , Physiology , Cyclic AMP-Dependent Protein Kinases , Physiology , Flavonoids , Pharmacology , Therapeutic Uses , L-Lactate Dehydrogenase , Metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Signal Transduction , Synaptosomes , Chemistry
15.
Article in English | WPRIM | ID: wpr-78633

ABSTRACT

The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins. In addition, CCL21 did not affect the mRNA levels of SERCA2 or its interacting protein Hax-1. Interestingly, SERCA2 expression was inversely related to DC migration in response to chemokine stimulation. The migratory capacity of CCL21-treated mDCs was decreased by the phospholipase C inhibitor U73122 and by the protein kinase C inhibitor BAPTA-AM. The migratory capacities of mDCs were increased in response to SERCA2 siRNA expression but were decreased by SERCA2 overexpression. In addition, DCs treated with a SERCA2-specific inhibitor (cyclopiazonic acid) had significantly increased migratory capacities as mDCs regardless of SERCA2 expression. Moreover, SERCA2 expression was dependent on DC maturation induced by cytokines or Toll-like receptor agonists. Therefore, the migratory capacities differed in differentially matured DCs. Taken together, these results suggest that SERCA2 contributes to the migration of CCL21-activated DCs as an important feature of the adaptive immune response and provide novel insights regarding the role of SERCA2 in DC functions.


Subject(s)
Adaptive Immunity , Adenosine Triphosphatases , Chemokine CCL21 , Chemokines , Cytokines , Dendritic Cells , Mitogen-Activated Protein Kinases , Protein Kinase C , Receptors, Chemokine , RNA, Messenger , RNA, Small Interfering , Sarcoplasmic Reticulum , Toll-Like Receptors , Type C Phospholipases
16.
Immune Network ; : 249-255, 2016.
Article in English | WPRIM | ID: wpr-97829

ABSTRACT

Exogenous nucleic acids induce an innate immune response in mammalian host cells through activation of the retinoic acid-inducible gene I (RIG-I). We evaluated RIG-I protein for RNA binding and ATPase stimulation with RNA ligands to investigate the correlation with the extent of immune response through RIG-I activation in cells. RIG-I protein favored blunt-ended, double-stranded RNA (dsRNA) ligands over sticky-ended dsRNA. Moreover, the presence of the 5'-triphosphate (5'-ppp) moiety in dsRNA further enhanced binding affinity to RIG-I. Two structural motifs in RNA, blunt ends in dsRNA and 5'-ppp, stimulated the ATP hydrolysis activity of RIG-I. These structural motifs also strongly induced IFN expression as an innate immune response in cells. Therefore, we suggest that IFN induction through RIG-I activation is mainly determined by structural motifs in dsRNA that increase its affinity for RIG-I protein and stimulate ATPase activity in RIG-I.


Subject(s)
Adenosine Triphosphatases , Adenosine Triphosphate , Hydrolysis , Immunity, Innate , Interferon Type I , Ligands , Nucleic Acids , RNA , RNA, Double-Stranded
17.
Article in English | WPRIM | ID: wpr-201384

ABSTRACT

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.


Subject(s)
Adenosine Triphosphatases , Adenosine Triphosphate , Binding Sites , Cell Proliferation , DNA Topoisomerases, Type II , Heat-Shock Proteins , Histidine , Hot Temperature , Humans , Phosphotransferases
18.
Article in Chinese | WPRIM | ID: wpr-261153

ABSTRACT

Progressive familial intrahepatic cholestasis type I (PFIC1) is an autosomal recessive disorder caused by biallelic mutations of ATP8B1 gene, with progressive cholestasis as the main clinical manifestation. This paper reports the clinical and genetic features of a PFIC1 patient definitely diagnosed by ATP8B1 genetic analysis. The patient, a boy aged 14 months, was referred to the hospital with the complaint of jaundiced skin and sclera over 10 months. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. On physical examination, hepatosplenomegaly was discovered in addition to jaundice of the skin and sclera. The liver was palpable 4 cm below the right subcostal margin and 2 cm below the xiphoid while the spleen 2 cm below the left subcostal margin. The liver function test revealed elevated levels of serum total bile acids, bilirubin, and transaminases; however, the γ-glutamyl transferase level was normal. The diagnosis was genetic cholestasis of undetermined origin. At the age of 1 year and 8 months, a Roux-en-Y cholecystocolonic bypass operation was performed, and thereafter the jaundice disappeared. At 5 years and 1 month, via whole genome sequencing analysis and Sanger sequencing confirmation, the boy was found to be a homozygote of mutation c.2081T>A(p.I694N) of ATP8B1 gene, and thus PFIC1 was definitely diagnosed. The boy was followed up until he was 6 years, and jaundice did not recur, but the long-term outcome remains to be observed.


Subject(s)
Adenosine Triphosphatases , Genetics , Cholestasis, Intrahepatic , Genetics , DNA Mutational Analysis , Humans , Infant , Male , Mutation , Sequence Analysis, DNA
19.
Article in Chinese | WPRIM | ID: wpr-287956

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the features of genetic mutations underlying Wilson's disease and provide prenatal and presymptomatic diagnosis.</p><p><b>METHODS</b>For 35 pedigrees affected with the disease, the exons and exon-intron boundaries of the ATP7B gene were amplified with polymerase chain reaction and subjected to Sanger sequencing. After the genotypes of parents of the probands were determined, prenatal diagnosis were performed through chorionic villus sampling.</p><p><b>RESULTS</b>The overall rate for mutation detection was 92.9%. A total of 24 distinct mutations were detected, which included 7 novel mutations, i.e., c.3871G>A(p.A1291T), c.2593_2594insGTCA, c.2790_2792delCAT, c.3661_3663delGGG, c.3700delG, c.4094_4097delCTGT, and IVS6+1G>A. Three mutations, including R778L (c.2333G>T)(45.7%), A874V (c.2621C>T)(7.1%) and P992L (c.2975C>T)(7.1%), were relatively common. Two presymptomatic patients were detected through familial screening, for whom treatment was initiated. Prenatal genetic diagnosis has verified three healthy fetuses and one carrier.</p><p><b>CONCLUSION</b>In this study the most popular mutation ofATP7B gene is R778L and 7 novel mutations have been identified in this gene. For pedigrees of Wilson's disease, genetic counseling in addition with prenatal and presymptomatic diagnosis should be provided through Sanger sequencing and haplotype analysis.</p>


Subject(s)
Adenosine Triphosphatases , Genetics , Adult , Base Sequence , Cation Transport Proteins , Genetics , Copper-Transporting ATPases , DNA Mutational Analysis , Female , Genotype , Hepatolenticular Degeneration , Embryology , Genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , Pedigree , Pregnancy , Prenatal Diagnosis
20.
Chinese Medical Journal ; (24): 2497-2501, 2016.
Article in English | WPRIM | ID: wpr-307386

ABSTRACT

<p><b>OBJECTIVE</b>The aim of this study was to help people comprehensively understand the research advances related to ring finger protein 213 (RNF213) in moyamoya disease (MMD) and to understand the disease at the molecular level to provide a new perspective of the diagnosis of the disease.</p><p><b>DATA SOURCES</b>This review was based on data in articles published between 2005 and 2015 that were retrieved from the PubMed database. The search terms included RNF213, MMD, intracranial major artery stenosis /occlusion (ICASO), genotype, phenotype, mutant and variants, and the combinations of these terms.</p><p><b>STUDY SELECTION</b>Articles related to MMD and RNF213 were selected for review, and we also reviewed publications related to ICASO.</p><p><b>RESULTS</b>RNF213 is not only associated with MMD but also associated with intracranial major artery stenosis. In addition, RNF213 variants exhibit apparent ethnic diversity; specifically, the c.14576G>A variant is mainly detected in Korean, Chinese, and Japanese populations, particularly the latter population. The genotypes of RNF213 correlate with the phenotypes of MMD; for example, the homozygous c.14576G>A variant is associated with early-onset, severe symptoms, and an unfavorable prognosis. Furthermore, the RNF213 c.14576G>A variant should be considered during the diagnosis of MMD because no patients with quasi-MMD have been reported to carry the RNF213 c.14576G>A variant whereas 66 of 78 patients with definite MMD have been found to carry this variant.</p><p><b>CONCLUSIONS</b>The growing literature demonstrates that MMD is primarily caused by the synergy of genetic and environmental factors, and unknown genetic modifiers might play roles in the etiology of MMD. Further research should be conducted to clarify the pathogenic mechanism of MMD.</p>


Subject(s)
Adenosine Triphosphatases , Genetics , Animals , Asian Continental Ancestry Group , Genetic Predisposition to Disease , Genotype , Humans , Moyamoya Disease , Genetics , Phenotype , Ubiquitin-Protein Ligases , Genetics
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