共查询到20条相似文献,搜索用时 8 毫秒
1.
In the early 1980s, we proposed a unifying
model for β-cell damage (The OKAMOTO
model), in which poly(ADP-ribose) synthetase/
polymerase (PARP) activation plays an
essential role in the consumption of NAD+,
which leads to energy depletion and necrotic
cell death. In 1984, we demonstrated that the
administration of PARP inhibitors to 90% depancreatized
rats induces islet regeneration.
From the regenerating islet-derived cDNA
library we isolated Reg (Regenerating Gene)
and demonstrated that Reg protein induces βcell
replication via the Reg receptor and ameliorates
experimental diabetes. More recently,
we showed that the combined addition of IL-6
and dexamethasone induces the Reg gene expression in β-cells and that PARP inhibitors
enhance the expression. In 1993, we found that
cyclic ADP-ribose (cADPR), a product synthesized
from NAD+, is a second messenger for
intracellular Ca+ mobilization for insulin secretion
by glucose, and proposed a novel mechanism
of insulin secretion, the CD38-cADPR signal
system.
Therefore, PARP inhibitors prevent β-cell
necrosis, induce β-cell replication and maintain
insulin secretion. In this paper, we would like to present a perspective
view based on our studies concerning
cell death, cell regeneration, and cell function,
especially on insulin-producing pancreatic βcells,
in the processes of which poly(ADPribose)
synthetase/polymerase (PARP) and
cyclic ADP-ribose (cADPR) are functioning. 相似文献
2.
Chemical composition, origin, and biological role of the surface coat (SC) of plant-parasitic nematodes are described and compared with those of animal-parasitic and free-living nematodes. The SC of the plant-parasitic nematodes is 5-30 nm thick and is characterized by a net negative charge. It consists, at least in part, of glycoproteins and proteins with various molecular weights, depending upon the nematode species. The lability of its components and the binding of human red blood cells to the surface of many tylenchid plant-parasitic nematodes, as well as the binding of several neoglycoproteins to the root-knot nematode Meloidogyne, suggest the presence of carbohydrate-recognition-domains for host plants and parasitic or predatory soil microorganisms (Pasteuria penetrans and Dactylaria spp., for example). These features may also assist in nematode adaptations to soil environments and to plant hosts with defense mechanisms that depend on reactions to nematode surfaces. Surface coat proteins can be species and race specific, a characteristic with promising diagnostic potential. 相似文献
3.
W. Zhuang Y. Z. Chen E. W. Prohofsky 《Journal of biomolecular structure & dynamics》2013,31(2):403-414
Abstract We study the contribution of various vibrational modes to the melting of poly(dG) · poly(dC). We find that the principal contribution comes from the H-bond breathing modes that have been observed in Raman scattering and that we have associated with helix melting. We show the softening of these modes on approach to melting in agreement with the observed behavior. We also describe the contribution to melting from base rotation modes that others have suggested are important in melting. 相似文献
4.
A new approach to the synthesis of isoflavones and 2′-hydroxyisoflavones, useful intermediates for synthesis of pterocarpinoids, are described. The 2′-hydroxyisoflavone (VIII; R=CH3, R′=H) synthesized by this method, was converted into (±)-pterocarpin (VII; R=CH3, R′=H). Attempts to obtain the corresponding isoflavane or isoflavene from the coumarine (XVII) failed. 相似文献
5.
John N. Prebble 《Journal of the history of biology》2013,46(4):699-737
Attempts to solve the puzzling problem of oxidative phosphorylation led to four very different hypotheses each of which suggested a different view of the ATP synthase, the phosphorylating enzyme. During the 1960s and 1970s evidence began to accumulate which rendered Peter Mitchell’s chemiosmotic hypothesis, the novel part of which was the proton translocating ATP synthase (ATPase), a plausible explanation. The conformational hypothesis of Paul Boyer implied an enzyme where ATP synthesis was driven by the energy of conformational changes in the respiratory proteins. This was finally abandoned as an explanation of the overall process. Nevertheless the conformational understanding of the enzyme became an acceptable proposal during the early 1970s and eventually led Boyer to a view of the enzyme that incorporated both hypotheses. The correspondence between Mitchell and Boyer, both Nobel laureates, exposes their different approaches to both this enzyme and to the hypotheses of oxidative phosphorylation and illuminates a key step in the development of bioenergetics. In particular Boyer was suspicious of proton gradients, because he could not envisage a chemical mechanism for the synthesis of ATP, while Mitchell distrusted conformational arguments because he believed the proton must act vectorially at the active site of the enzyme. This resulted in two different views of the mechanisms operating in this enzyme. Ultimately while Boyer was able to marry the two approaches, Mitchell retained his insistence on the role of the proton at the active site and was thus unable to give significance to Boyer’s conformational ideas. The underlying issues in this debate are discussed particularly with reference to the differing styles of Boyer and Mitchell and the influence of molecular biology, especially the development of protein technology. 相似文献
6.
Piet Herdewijn Jan Balzarini Rudi Pauwels Gerard Janssen Arthur Van Aerschot Erik De Clercq 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1231-1257
Abstract The mono- and diamino analogues of 9-(2-deoxy-α-D-erythro-pen-tofuranosyl)adenine la, 9-(2-deoxy-α-D-threo-pentofuranosyl)adenine 4a, 9-(3-deoxy-α-D-erythro-pentofuranosyl)adenine 2a and 9-(3-deoxy-α-D-threo-pentofuranosyl)adenine 3a were synthesized by triphenylphosphine reduction of the corresponding azido compounds. The azido group was introduced by a substitution reaction with lithium azide on mesylates or, more directly, by reaction with lithium azide, triphenylphosphine and carbon tetrabromide. Of the newly synthesized compounds, only 3′-amino-2′,3′-dideoxyadenosine proved, albeit slightly, inhibitory to murine leukemia L1210 and mammary carcinoma FM3A, and human B-lymphoblast Raji, T-lymphoblast Molt/4F and T-lymphocyte MT-4 cell proliferation in vitro (50 % inhibitory dose : 43.1-323 μM). None of the compounds inhibited human immunodeficiency virus-induced cytopathogenicity in MT-4 cells. 相似文献
7.
Goutam Gupta Mukti H. Sarma M. M. Dhingra Ramaswamy H. Sarma Malini Rajagopalan V. Sasisekharan 《Journal of biomolecular structure & dynamics》2013,31(2):395-416
Abstract Poly(dA-dT)?poly(dA-dT) can adopt the B- and D- forms in the fibrous state. Theoretical energy calculations and fiber diffraction analyses suggest that there can be three structural models of poly(dA-dT)?poly(dA-dT) in each of these two forms viz right and left-handed Watson Crick models and left-handed Hoogsteen—a total of six possible models. Fiber data for the polymer in the B- or the D-form or energy calculations cannot distinguish any one model from the other. However, a comparison of observed proton chemical shifts with the theoretically computed ones and the NOE studies on exchangeable and nonexchangeable protons suggest that poly(dA-dT)?poly(dA-dT) in low salt solution exists predominantly in the left-handed B-conformation. 相似文献
8.
Entomological Review - The life cycle, trophic associations, distribution, and harmfulness of an invasive seed beetle species, Megabruchidius dorsalis (Fåhraeus, 1839) were studied in the... 相似文献
9.
B. Bayard L. D. Leserman C. Bisbal G. Huez M. Silhol B. Lebleu 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):157-160
Abstract 5’ and 2’ stabilized (2′-5′)(A)n analogues were synthesized by chemical modifications of enzymatically polymerized (2′-5′)(A)n oligomers. They exhibit an increased antiviral activity after micro-injection in HeLa cell cytoplasm in agreement with their augmented metabolic stability. Their specific in vitro delivery to mouse leukemia cells after encapsulation in targetted liposomes leads to a transient inhibition of protein synthesis and an antiviral activity. 相似文献
10.
Ninad M. Walavalkar Nathaniel Gordon David C. Williams Jr. 《The Journal of biological chemistry》2013,288(5):3419-3427
The methyl-cytosine binding domain 2 (MBD2)-nucleosome remodeling and deacetylase (NuRD) complex recognizes methylated DNA and silences expression of associated genes through histone deacetylase and nucleosome remodeling functions. Our previous structural work demonstrated that a coiled-coil interaction between MBD2 and GATA zinc finger domain containing 2A (GATAD2A/p66α) proteins recruits the chromodomain helicase DNA-binding protein (CHD4/Mi2β) to the NuRD complex and is necessary for MBD2-mediated DNA methylation-dependent gene silencing in vivo (Gnanapragasam, M. N., Scarsdale, J. N., Amaya, M. L., Webb, H. D., Desai, M. A., Walavalkar, N. M., Wang, S. Z., Zu Zhu, S., Ginder, G. D., and Williams, D. C., Jr. (2011) p66α-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc. Natl. Acad. Sci. U.S.A. 108, 7487–7492). The p66α-MBD2 interaction differs from most coiled-coils studied to date by forming an anti-parallel heterodimeric complex between two peptides that are largely monomeric in isolation. To further characterize unique features of this complex that drive heterodimeric specificity and high affinity binding, we carried out biophysical analyses of MBD2 and the related homologues MBD3, MBD3-like protein 1 (MBD3L1), and MBD3-like protein 2 (MBD3L2) as well as specific mutations that modify charge-charge interactions and helical propensity of the coiled-coil domains. Analytical ultracentrifugation analyses show that the individual peptides remain monomeric in isolation even at 300 μm in concentration for MBD2. Circular dichroism analyses demonstrate a direct correlation between helical content of the coiled-coil domains in isolation and binding affinity for p66α. Furthermore, complementary electrostatic surface potentials and inherent helical content of each peptide are necessary to maintain high-affinity association. These factors lead to a binding affinity hierarchy of p66α for the different MBD2 homologues (MBD2 ≈ MBD3 > MBD3L1 ≈ MBD3L2) and suggest a hierarchical regulatory model in tissue and life cycle stage-specific silencing by NuRD complexes. 相似文献
11.
T. P. Prakash R. Krishnakumar K. N. Ganesh 《Nucleosides, nucleotides & nucleic acids》2013,32(7):713-728
Abstract Synthesis and spectroscopic characterization of a dinucleotide dTprA 2 having imidazole containing side chain at C8 of adenine and aminoethylamino side chain at C5′ of nucleosugar is presented. Spectroscopic results suggest that such modifications do not drastically change the conformation of the new molecule relative to that of parent derivative. An anti glycosyl torsion would place the C8-conjugated histamine close to phosphate in right orientation for putative intramolecular interaction as in ribonuclease catalytic site. 相似文献
12.
Tokuo Itoh Tomokazu Sugawara Yoshihisa Mizuno 《Nucleosides, nucleotides & nucleic acids》2013,32(2):179-190
Abstract A novel route for the preparation of 7-amino-3-(β-D-ribofuranosyl)-3H-imidazo [4,5-b] pyridine (1-deazaadenosine) has been developed. Synthesis of 5′-deoxy-5′-isobutylthio-1-deazaadenosine (1-deazaSIBA) and S-(1-deazaadenosyl)-homocysteine (1-deazaSAH) is also described. 相似文献
13.
Abstract We have studied by X-ray diffraction fibers of complexes of poly(dG)·poly(dC) with N-α-acetyl-L-arginine ethylamide. Although these polynucleotides favour the A form of DNA, in this complex it is never found, thus confirming that arginine prevents the appearance of this form of DNA At high relative humidity the B form is present. Upon dehydration two new structures appear. One of them is a triple helix, most likely formed by poly(dC+) · poly(dG) · poly(dC). The other structure found also has features which indicate a multistranded conformation. 相似文献
14.
Jun-ya Takahashi Kenji Mori Masanao Matsui 《Bioscience, biotechnology, and biochemistry》2013,77(7):1605-1606
Crystalline aromatic l-amino acid decarboxylase from Micrococcus percitreus is inactive in the absence of pyridoxal phosphate (PLP). The inactive form of the enzyme shows absorption at 340 nm and contains one mol of PLP per mol of enzyme. Binding of PLP to the inactive form is accompanied by a pronounced increase in absorbance at 415 nm. The amount of PLP that binds to this holoenzyme is 2 mol per mol of enzyme. The inactive half-resolved form, i. e. semiapoenzyme, is obtained again by dialysis of the holoenzyme against phosphate buffer. When the semiapoenzyme is dialyzed against phosphate buffer containing 3,4-dihydroxyphenyl-l-alanine, it loses the absorption at 340 nm with the loss of PLP. This apoenzyme regains the activity and absorption at 340 nm and 415 nm on association with PLP. 相似文献
15.
16.
George I. Birnbaum Jerzy Giziewicz Tai-Shun Lin William H. Prusoff 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1259-1269
Abstract The structure and conformation of 2′,3′-dideoxy-2′,3′-didehydrocytidine (2′,3′-dideoxycytidin-2′-ene, d4C), a potent inhibitor of the human immunodeficiency virus, was determined by X-ray crystallography. The nucleoside crystallizes in the orthorhombic space group P212121 with cell dimensions a = 8.603(1), b = 9.038(1), c = 25.831(2) A and with two independent molecules in the asymmetric unit (Z = 8). Atomic parameters were refined by full-matrix least squares to a final value of R = 0.033 for 2258 observed reflections. The molecules are quite flexible: in molecule A the glycosyl torsion angle (XCN) is 61.3° and the -CH2OH side chain is in the gauche + orientation while in molecule B XCN = 19.8° and the side chain is trans. The five-membered rings are slightly puckered (~0.1 Å), 04′ being endo in molecule A and exo in molecule B. A mechanism is proposed for the known instability of 2′,3′-unsaturated nucleosides. 相似文献
17.
Lakhvir Kaur Kanwaldeep Singh Surinder Paul Sukhprit Singh Shashank Singh Subheet Kumar Jain 《AAPS PharmSciTech》2018,19(4):1606-1624
Type of biological membrane used in skin permeation experiment significantly affects skin permeation and deposition potential of tested formulations. In this study, a comparative study has been carried out to evaluate the potential of a synthetic membrane (Strat-M?) with rat, human, and porcine ear skin to carry out skin permeation study of nanoformulations of a high molecular weight drug, amphotericin B. Results demonstrated that the permeation of this high molecular weight drug through Strat-M? showed close similitude to human skin. Value of correlation coefficient (R2) of log diffusion between Strat-M? and human skin was found to be 0.99 which demonstrated the similarities of Strat-M? membrane to the human skin. In similarity factor analysis, the value of f2 was also found to be 85, which further demonstrated the similarities of Strat-M? membrane to human skin. Moreover, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET) analysis of synthetic and biological membranes depicted almost similar morphological features (thickness, pore size, surface morphology, and diameter) of synthetic membrane with human skin. The results of the study demonstrated Strat-M? as a better alternative to carry out skin permeation experiment due to the consistent results, reproducibility, easy availability, and minimum variability with human skin. 相似文献
18.
19.
Marie Lechaftois Elise Dreano Bruno Palmier Isabelle Margaill Catherine Marchand-Leroux Christilla Bachelot-Loza Dominique Lerouet 《PloS one》2014,9(10)