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Mousumi Pal, Utpal Nandi, Debaraj Mukherjee
Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation...
March 7, 2018: European Journal of Medicinal Chemistry
Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
Stefan Ilic, Usha Pandey Kadel, Yasemin Basdogan, John A Keith, Ksenija D Glusac
Thermodynamic hydricities (ΔGH- ) in acetonitrile and dimethyl sulfoxide have been calculated and experimentally measured for several metal-free hydride donors: NADH analogs (BNAH, CN-BNAH, Me-MNAH, HEH), methylene tetrahydromethanopterin analogs (BIMH, CAFH), acridine derivatives (Ph-AcrH, Me2 N-AcrH, T-AcrH, 4OH, 2OH, 3NH) and a triarylmethane derivative (6OH). The calculated hydricity values, obtained using density functional theory, showed a reasonably good match (within 3 kcal/mol) with the experimental values, obtained using "potential-pKa" and "hydride-transfer" methods...
March 16, 2018: Journal of the American Chemical Society
Seow Theng Ong, Madhavi Latha Somaraju Chalasani, M H U Turabe Fazil, Praseetha Prasannan, Atish Kizhakeyil, Graham D Wright, Dermot Kelleher, Navin Kumar Verma
Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP), also known as AKAP450, is a cytosolic scaffolding protein involved in the targeted positioning of multiple signaling molecules, which are critical for cellular functioning. Here, we show that CG-NAP is predominantly expressed in human primary T-lymphocytes, localizes in close proximity (<0.2 μm) with centrosomal and Golgi structures and serves as a docking platform for Protein Kinase A (PKA). GapmeR-mediated knockdown of CG-NAP inhibits LFA-1-induced T-cell migration and impairs T-cell chemotaxis toward the chemokine SDF-1α...
2018: Frontiers in Immunology
Xiaoqun Zhang, Ioannis Mantas, Alexandra Alvarsson, Takashi Yoshitake, Mohammadreza Shariatgorji, Marcela Pereira, Anna Nilsson, Jan Kehr, Per E Andrén, Mark J Millan, Karima Chergui, Per Svenningsson
The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (β-PEA) compared to 3-iodothyronamine (T1 AM). Immunoblotting and amperometry were performed in dorsal striatal slices from wild-type (WT) and TAAR1 knockout (KO) mice. T1 AM increased TH phosphorylation at both Ser19 and Ser40 , actions that should promote functional activity of TH...
2018: Frontiers in Pharmacology
Chengyuan Lin, Jin Bai, Mulan He, Anderson O L Wong
In this study, structural analysis of grass carp prolactin (PRL) gene was performed and the signaling mechanisms for pituitary adenylate cyclase-activating peptide (PACAP) regulation of PRL promoter activity were investigated. In αT3-1 cells, PRL promoter activity could be induced by oPACAP38 which was blocked by PACAP antagonist but not the VIP antagonist. The stimulatory effect of oPACAP38 was mimicked by activation of AC/cAMP and voltage-sensitive Ca2+ channel (VSCC) signaling, or induction of Ca2+ entry...
March 15, 2018: Scientific Reports
Nourdine Chakouri, Cyril Reboul, Doria Boulghobra, Adrien Kleindienst, Stéphane Nottin, Sandrine Gayrard, François Roubille, Stefan Matecki, Alain Lacampagne, Olivier Cazorla
BACKGROUND: The interplay between oxidative stress and other signaling pathways in the contractile machinery regulation during cardiac stress and its consequences on cardiac function remains poorly understood. We evaluated the effect of the crosstalk between β-adrenergic and redox signaling on post-translational modifications of sarcomeric regulatory proteins, Myosin Binding Protein-C (MyBP-C) and Troponin I (TnI). METHODS AND RESULTS: We mimicked in vitro high level of physiological cardiac stress by forcing rat hearts to produce high levels of oxidized glutathione...
May 1, 2018: International Journal of Cardiology
Li Wang, Yang Li, Na Ning, Jin Wang, Zi Yan, Suli Zhang, Xiangying Jiao, Xiaohui Wang, Huirong Liu
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1 -adrenergic receptor autoantibodies (β1 -AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1 -AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1 -AAB-immunized rat model...
March 14, 2018: Cell Death & Disease
Cheng-Han Yu, Chi-Chi Chou, Der-Yen Lee, Kay-Hooi Khoo, Geen-Dong Chang
Phenyl vinyl sulfone (PVS) and phenyl vinyl sulfonate (PVSN) inactivate protein tyrosine phosphatases (PTPs) by mimicking the phosphotyrosine structure and providing a Michael addition acceptor for the active-site cysteine residue of PTPs, thus forming covalent adducts between PVS (or PVSN) and PTPs. We developed a specific antiserum against PVS. This antiserum can be used in general antibody-based assays such as immunoblotting, immunofluorescence staining, and immunoprecipitation. Target identification through immunoprecipitation and mass spectrometry analysis reveals potential targets of PVS, mostly proteins with reactive cysteine residues or low-pKa cysteine residues that are prone to reversible redox modifications...
March 14, 2018: Bioscience Reports
Etta Y L Liu, Miranda L Xu, Yan Jin, Qiyun Wu, Tina T X Dong, Karl W K Tsim
Genistein, 4',5,7-trihydroxyisoflavone, is a major isoflavone in soybean, which is known as phytestrogen having known benefit to brain functions. Being a common phytestrogen, the possible role of genistein in the brain protection needs to be further explored. In cultured PC12 cells, application of genistein significantly induced the expression of neurofilaments (NFs), markers for neuronal differentiation. In parallel, the expression of tetrameric form of proline-rich membrane anchor (PRiMA)-linked acetyl-cholinesterase (G4 AChE), a key enzyme to hydrolyze acetylcholine in cholinergic synapses, was induced in a dose-dependent manner: this induction included the associated protein PRiMA...
2018: Frontiers in Molecular Neuroscience
Ao Shen, Madeline Nieves-Cintron, Yawen Deng, Qian Shi, Dhrubajyoti Chowdhury, Jinyi Qi, Johannes W Hell, Manuel F Navedo, Yang K Xiang
G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in a broad range of physiological responses and disease states. Activated GPCRs can undergo agonist-induced phosphorylation by G protein receptor kinases (GRKs) and second messenger-dependent protein kinases such as protein kinase A (PKA). Here, we characterize spatially segregated subpopulations of β2 -adrenergic receptor (β2 AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric β2 ARs that undergo endocytosis, whereas PKA modifies dimeric β2 ARs that remain at the cell surface...
March 13, 2018: Nature Communications
Hyemi Bae, Jeongyoon Choi, Young-Won Kim, Donghee Lee, Jung-Ha Kim, Jae-Hong Ko, Hyoweon Bang, Taeho Kim, Inja Lim
This study investigated the expression of voltage-gated K⁺ (KV ) channels in human cardiac fibroblasts (HCFs), and the effect of nitric oxide (NO) on the KV currents, and the underlying phosphorylation mechanisms. In reverse transcription polymerase chain reaction, two types of KV channels were detected in HCFs: delayed rectifier K⁺ channel and transient outward K⁺ channel. In whole-cell patch-clamp technique, delayed rectifier K⁺ current (IK ) exhibited fast activation and slow inactivation, while transient outward K⁺ current (Ito ) showed fast activation and inactivation kinetics...
March 12, 2018: International Journal of Molecular Sciences
Yinghang Liu, Kunlong Yang, Qiuping Qin, Guinan Lin, Tianran Hu, Zhangling Xu, Shihua Wang
The heterotrimeric G proteins are critical for signal transduction and function in numerous biological processes including vegetative growth, asexual development and fungal virulence in fungi. Here, we identified four G protein alpha subunits (GanA, GpaB, FadA and GaoC) in the notorious Aflatoxin-producing fungus Aspergillus flavus . GanA, GpaB and FadA have homologues in other fungal species, while GaoC is a novel one. Here, we showed that the loss function of gpaB displayed a defect in conidiophore formation and considerably reduced expression levels of conidia-specific genes brlA and abaA ...
March 10, 2018: Toxins
Qiwei Chen, Liang Zhu, Huafeng Zong, Xishuang Song, Lina Wang, Xuejian Wang, Deyong Yang, Jianbo Wang
We previously found that in normal epithelia of the prostate, localization of AQP3 is limited to the cell membranes; however, the expression of AQP3 protein in cancer epithelia is distributed to the plasma. Yet, the detailed mechanism remains unclear. In the present study, PC‑3 cell derivatives with stable knockdown of RAS like proto‑oncogene A (RalA) and overexpression of E‑cadherin were established. We found that overexpression of E‑cadherin and knockdown of RaLA resulted in an increase in AQP3 in prostate cancer cell plasma membranes...
March 9, 2018: Oncology Reports
Haotian Lei, Bruce E Bowler
Structural studies of yeast iso-1-cytochrome c (L.J. McClelland, T.-C. Mou, M.E. Jeakins-Cooley, S.R. Sprang, B.E. Bowler, Proc. Natl. Acad. Sci. U.S.A. 111 (2014) 6648-6653) show that modest movement of Ω-loop D (residues 70-85, average RMSD versus the native structure: 0.81 Å) permits loss of Met80-heme ligation creating an available coordination site to catalyze the peroxidase activity mediated by cytochrome c early in apoptosis. However, Ala81 and Gly83 move significantly (RMSDs of 2.18 and 1.26 Å, respectively)...
February 27, 2018: Journal of Inorganic Biochemistry
Thai Ha Tran, Jérôme Labanowski, Hervé Gallard
The manganese oxide birnessite adsorbed and catalyzed the transformation of the anthelminthic drug niclosamide (NIS) into 2-chloro-4-nitroaniline (CNA) and 5-chlorosalicylic acid (CSA) at acidic pH. The adsorption of NIS was fitted using a linear isotherm for all conditions and reaction times. Linear adsorption constant Kd was 103 000 L kg-1 at pH 5.0. The rate of transformation was first order with respect to both MnO2 and NIS. At pH 5.0, the second order rate constant was 3.3 (±0.3) × 10-1  M-1  s-1 ...
March 6, 2018: Chemosphere
Wei Bai, Ping Li, Ya-Lei Ning, Yan Peng, Ren-Ping Xiong, Nan Yang, Xing Chen, Yuan-Guo Zhou
Glutamate transporters (EAATs) on cerebral vascular endothelial cells play an important role in maintaining glutamate homeostasis in the brain. The dysfunction of endothelial EAATs is an important reason for the dramatically elevated brain glutamate levels after brain injury, such as traumatic brain injury (TBI). The adenosine A2A receptor (A2A R) plays an important role in regulating the brain glutamate level after brain injury; however, researchers have not clearly determined whether this role was related to its ability to regulate endothelial EAATs...
March 8, 2018: Biochemical and Biophysical Research Communications
Mouli Saha, Promita Nandy, Mousumi Chakraborty, Piyal Das, Saurabh Das
pKa of a compound is crucial for determining the contributions of different forms of it towards overall binding with DNA. Hence it is important to use correct pKa values in DNA interaction studies. This study takes a look at the importance of pKa values to realize binding of compounds with DNA. Since pKa of a compound determined in the presence of DNA is quite different from that determined in its absence hence, presence of different forms of a compound during interaction with DNA is different from that realized if the determination of pKa is done in normal aqueous solution in absence of DNA...
February 6, 2018: Biophysical Chemistry
Isamara Julia Camuri, Adriano Batista Costa, Amando Siuiti Ito, Wallance Moreira Pazin
The bioactivity of propolis against several pathogens is well established, leading to the extensive consumption of that bee product to prevent diseases. Brazilian green propolis, collected by the species Apis mellifera, is one of the most consumed in the world. The chemical composition of green propolis is complex and it has been shown that it displays antioxidant, antimicrobial, anti-inflammatory and antitumor activities, especially due to the high content of Artepillin C. The molecule is a derivative of cinnamic acid with two prenylated groups, responsible for the improvement of the affinity of the compound for lipophilic environment...
February 23, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Deepak Bhandari, Brett A Bowman, Anish B Patel, David M Chambers, Víctor R De Jesús, Benjamin C Blount
This work describes a quantitative high-throughput analytical method for the simultaneous measurement of small aliphatic nitrogenous biomarkers, i.e., 1,6-hexamethylenediamine (HDA), isophoronediamine (IPDA), β-methylamino-l-alanine (BMAA), and trimethylamine N-oxide (TMAO), in human urine. Urinary aliphatic diamines, HDA and IPDA, are potential biomarkers of environmental exposure to their corresponding diisocyanates. Urinary BMAA forms as a result of human exposure to blue-green algae contaminated food. And, TMAO is excreted in urine due to the consumption of carnitine- and choline-rich diets...
March 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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