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571.
Effect of 21 days administration of sertraline (30 mg/kg, po) in streptozotocin (55 mg/kg, ip) induced diabetic and non-diabetic rats produced hypoglycemia in diabetic and non-diabetic rats. Pinacidil (1mg/kg, po), when co-administered with sertraline or glimepiride antagonized the decrease in glucose levels in diabetic rats. Pinacidil (10(-6)-10(-3) M) produced dose dependent relaxation (EC50-1.58 x 10(-5) M). Neither sertraline nor glimepiride had any effect on the resting tension of ileum preparation. Both sertraline and glimepiride antagonized competitively the pinacidil-induced relaxation. The pA2 values of sertraline and glimepiride reversal of pinacidil-induced relaxation were 5.5 and 6.2 respectively. These studies suggest the involvement of K+ channels in hypoglyceimic effects of sertraline. 相似文献
572.
Dimerization of peptides can provide high binding entities to serve as targeted diagnostics or therapeutics. We developed methods for the preparation of homo- and heterodimer peptides bearing functional molecules (affinity probes, chelating ligands, or latent conjugating moieties). Monomer peptides, optionally bearing spacer groups, are tethered using a bifunctional linker, (di-succinimidyl glutarate, DSG) to provide the dimers. Protected or unprotected peptides can be employed for dimer assembly. Multiple lysine N(epsilon)-amino groups are controlled using the (4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (ivDde) protecting group. Functional molecules are optionally incorporated into the component peptides or into the assembled dimer. The methods are efficient and scaleable. 相似文献
573.
Roberts MT Phelan R Erlichman BS Pillai RN Ma L Lopreato GF Mihic SJ 《The Journal of biological chemistry》2006,281(6):3305-3311
Alcohols and volatile anesthetics enhance the function of inhibitory glycine receptors (GlyRs). This is hypothesized to occur by their binding to a pocket formed between the transmembrane domains of individual alpha1 GlyR subunits. Because GlyRs are pentameric, it follows that each GlyR contains up to five alcohol/anesthetic binding sites, with one in each subunit. We asked how many subunits per pentamer need be bound by drug in order to enhance receptor-mediated currents. A cysteine mutation was introduced at amino acid serine 267 (S267C) in the transmembrane 2 domain as a tool to block GlyR potentiation by some anesthetic drugs and to provide a means for covalent binding by the small, anesthetic-like thiol reagent propyl methanethiosulfonate. Xenopus laevis oocytes were co-injected with various ratios of wild-type (wt) to S267C alpha1 GlyR cDNAs in order to express heteromeric receptors with a range of wt:mutant subunit stoichiometries. The enhancement of GlyR currents by 200 mm ethanol and 1.5 mm chloroform was positively correlated with the number of wt subunits found in heteromeric receptors. Furthermore, currents from oocytes injected with high ratios of wt to S267C cDNAs (up to 200:1) were significantly and irreversibly enhanced following propyl methanethiosulfonate labeling and washout, demonstrating that drug binding to a single subunit in the receptor pentamer is sufficient to induce enhancement of GlyR currents. 相似文献
574.
Effect of supplementation of recombinant Regucalcin in extender on cryopreservation of spermatozoa of water buffalo (Bubalus bubalis) 下载免费PDF全文
575.
576.
Sandhya Noronha Lauren A. C. Alt Taylor E. Scimeca Omran Zarou Justyna Obrzut Brian Zanotti Elizabeth A. Hayward Akhil Pillai Shubha Mathur Joseph Rojas Ribhi Salamah Nalini Chandar Michael J. Fay 《In vitro cellular & developmental biology. Animal》2018,54(1):71-84
Liposarcoma is a malignant soft tissue tumor that originates from adipose tissue and is one of the most frequently diagnosed soft tissue sarcomas in humans. There is great interest in identifying novel chemotherapeutic options for treating liposarcoma based upon molecular alterations in the cancer cells. The Aurora kinases have been identified as promising chemotherapeutic targets based on their altered expression in many human cancers and cellular roles in mitosis and cytokinesis. In this study, we investigated the effects of an Aurora kinase A inhibitor (MK-5108), an Aurora kinase B inhibitor (AZD1152-HQPA), and a pan-Aurora kinase inhibitor (AMG 900) on undifferentiated SW-872 and well-differentiated 93T449 human liposarcoma cells. Treatment of the SW-872 and 93T449 cells with MK-5108 (0–1000 nM), AZD1152-HQPA (0–1000 nM), and AMG 900 (0–1000 nM) for 72 h resulted in a dose-dependent decrease in the total viable cell number. Based upon the EC50 values, the potency of the three Aurora kinase inhibitors in the SW-872 cells was as follows: AMG 900 (EC50 = 3.7 nM) > AZD1152-HQPA (EC50 = 43.4 nM) > MK-5108 (EC50 = 309.0 nM), while the potency in the 93T449 cells was as follows: AMG 900 (EC50 = 6.5 nM) > AZD1152-HQPA (EC50 = 74.5 nM) > MK-5108 (EC50 = 283.6 nM). The percentage of polyploidy after 72 h of drug treatment (0–1000 nM) was determined by propidium iodide staining and flow cytometric analysis. AMG 900 caused a significant increase in polyploidy starting at 25 nM in the SW-872 and 93T449 cells, and AZD1152-HQPA caused a significant increase starting at 100 nM in the SW-872 cells and 250 nM in the 93T449 cells. The Aurora kinase A inhibitor MK-5108 did not significantly increase the percentage of polyploid cells at any of the doses tested in either cell line. The expression of Aurora kinase A and B was evaluated in the SW-872 cells versus differentiated adipocytes and human mesenchymal stem cells by real-time RT-PCR and Western blot analysis. Aurora kinase A and B mRNA expression was significantly increased in the SW-872 cells versus the differentiated adipocytes and human mesenchymal stem cells. Western blot analysis revealed a ~ 48 kDa immunoreactive band for Aurora kinase A that was not present in the differentiated adipocytes or the human mesenchymal stem cells. A ~ 39 kDa immunoreactive band for Aurora kinase B was detected in the SW-872 cells, differentiated adipocytes, and human mesenchymal stem cells. A smaller immunoreactive band for Aurora kinase B was detected in the SW-872 cells but not in the differentiated adipocytes and human mesenchymal stem cells, and this may reflect the expression of a truncated splice variant of Aurora kinase B that has been associated with poor patient prognosis. The 93T449 cells demonstrated decreased expression of Aurora kinase A and B mRNA and protein compared to the SW-872 cells, and also expressed the truncated form of Aurora kinase B. The results of these in vitro studies indicate that Aurora kinase inhibitors should be further investigated as possible chemotherapeutic agents for human liposarcoma. 相似文献
577.
Prasannan V. Anu Madathiparambil G. Madanan Ananthakrishnan J. Nair Gangaprasad A. Nair Govinda Pillai M. Nair Perumana R. Sudhakaran Padikara K. Satheeshkumar 《Molecular biotechnology》2018,60(4):302-309
Oligopeptidases are enzymes involved in the degradation of short peptides (generally less than 30 amino acids in size) which help pathogens evade the host defence mechanisms. Leptospira is a zoonotic pathogen and causes leptospirosis in mammals. Proteome analysis of Leptospira revealed the presence of oligopeptidase A (OpdA) among other membrane proteins. To study the role of oligopeptidase in leptospirosis, the OpdA of L. interrogans was cloned and expressed in Escherichia coli with a histidine tag (His-tag). The protein showed maximum expression at 37 °C with 0.5 mM of IPTG after 2 h of induction. Recombinant OpdA protein was purified to homogeneity using Ni-affinity chromatography. The purified OpdA showed more than 80% inhibition with a serine protease inhibitor but the activity was reduced to 30% with the cysteine protease inhibitor. The peptidase activity was increased significantly in the presence of Zn2+ at a neutral pH. Inhibitor assay indicate the presence of more than one active sites for peptidase activity as reported with the OpdA of E. coli and Salmonella. Over-expression of OpdA in E. coli BL21 (DE3) did not cause any negative effects on normal cell growth and viability. The role of OpdA as virulence factor in Leptospira and its potential as a therapeutic and diagnostic target in leptospirosis is yet to be identified. 相似文献
578.
Kristy J. Brown Haeri Seol Dinesh K. Pillai Binu-John Sankoorikal Catherine A. Formolo Jenny Mac Nathan J. Edwards Mary C. Rose Yetrib Hathout 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(11):2454-2461
Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. This article is part of a Special Issue entitled: An Updated Secretome. 相似文献
579.
The recirculating B cell pool contains two functionally distinct, long-lived, posttransitional, follicular B cell populations 总被引:3,自引:0,他引:3
Cariappa A Boboila C Moran ST Liu H Shi HN Pillai S 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(4):2270-2281
Disparate models for the development of peripheral B cells may reflect significant heterogeneity in recirculating long-lived B cells that have not been previously accounted for. We show in this study that the murine recirculating B cell pool contains two distinct, long-lived, posttransitional, follicular B cell populations. Follicular Type I IgM(low) B cells require Ag-derived and Btk-dependent signals for their development and make up the majority of cells in the recirculating follicular B cell pool. Follicular type II B cells do not require Btk- or Notch-2-derived signals, make up about a third of the long-lived recirculating B cell pool, and can develop in the absence of Ag. These two follicular populations exhibit differences in basal tyrosine phosphorylation and in BCR-induced proliferation, suggesting that they may represent functionally distinct populations of long-lived recirculating B cells. 相似文献
580.
Jitesh K. Pillai Sarkarai Venkadesh A. Abdul Ajees Barry P. Rosen Hiranmoy Bhattacharjee 《Biometals》2014,27(6):1263-1275
The ArsA ATPase is the catalytic subunit of the ArsAB As(III) efflux pump. It receives trivalent As(III) from the intracellular metallochaperone ArsD. The interaction of ArsA and ArsD allows for resistance to As(III) at environmental concentrations. A quadruple mutant in the arsD gene encoding a K2A/K37A/K62A/K104A ArsD is unable to interact with ArsA. An error-prone mutagenesis approach was used to generate random mutations in the arsA gene that restored interaction with the quadruple arsD mutant in yeast two-hybrid assays. A number of arsA genes with multiple mutations were isolated. These were analyzed in more detail by separation into single arsA mutants. Three such mutants encoding Q56R, F120I and D137V ArsA were able to restore interaction with the quadruple ArsD mutant in yeast two-hybrid assays. Each of the three single ArsA mutants also interacted with wild type ArsD. Only the Q56R ArsA derivative exhibited significant metalloid-stimulated ATPase activity in vitro. Purified Q56R ArsA was stimulated by wild type ArsD and to a lesser degree by the quadruple ArsD derivative. The F120I and D137V ArsAs did not show metalloid-stimulated ATPase activity. Structural models generated by in silico docking suggest that an electrostatic interface favors reversible interaction between ArsA and ArsD. We predict that mutations in ArsA propagate changes in hydrogen bonding and salt bridges to the ArsA–ArsD interface that affect their interactions. 相似文献