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1.
Andrea Venerando Oriano Marin Giorgio Cozza Victor H. Bustos Stefania Sarno Lorenzo Alberto Pinna 《Cellular and molecular life sciences : CMLS》2010,67(7):1105-1118
The ability of three isoforms of protein kinase CK1 (α, γ1, and δ) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide
reproducing its 1–28 sequence. Both substrates are readily phosphoylated by CK1δ and CK1α, but not by the γ isoform. Affinity
of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K
m 0.82 μM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected
despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1
is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and
on a remote docking site mapped to the K221RQK224 loop according to modeling and mutational analysis. 相似文献
2.
Sergiy Kostenko Mahmud Tareq Hassan Khan Ingebrigt Sylte Ugo Moens 《Cellular and molecular life sciences : CMLS》2011,68(2):289-301
The mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated
in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested
several diterpenoid alkaloids for their ability to suppress MK5 kinase activity. We identified noroxoaconitine as an ATP competitor
that inhibited the catalytic activity of MK5 in vitro (IC50 = 37.5 μM; K
i = 0.675 μM) and prevented PKA-induced nuclear export of MK5, a process that depends on kinase active MK5. MK5 is closely
related to MK2 and MK3, and noroxoaconitine inhibited MK3- and MK5- but not MK2-mediated phosphorylation of the common substrate
Hsp27. Molecular docking of noroxoaconitine into the ATP binding sites indicated that noroxoaconitine binds more strongly
to MK5 than to MK3. Noroxoaconitine and derivatives may help in elucidating the precise biological functions of MK5 and may
prove to have therapeutic values. 相似文献
3.
Yuk-Man Leung Kar-Lok Wong Chia-Huei Lin Chia-Chia Chao Chun-Hsiao Chou Li-Yun Chang Siao-Wei Chen Tzu-Hurng Cheng Yueh-Hsiung Kuo 《Cellular and molecular life sciences : CMLS》2010,67(1):147-156
Voltage-gated K+ (Kv) channels exhibit slow or C-type inactivation during continuous depolarization. A selective pharmacological agent targeting
C-type inactivation is hitherto lacking. Here, we report that 6β-acetoxy-7α-hydroxyroyleanone (AHR), a diterpenoid compound
isolated from Taiwania cryptomerioides, can selectively modify C-type inactivation of Kv1.2 channels. Extracellular, but not intracellular, AHR (50 μM) dramatically
accelerated the slow decay of Kv currents and left-shifted the steady-state inactivation curve. AHR blocked Kv currents with
an IC50 of 17.7 μM. AHR did not affect the kinetics and voltage-dependence of Kv1.2 channel activation. Channel block by AHR was
independent of intracellular K+ concentration. In addition, effect of AHR was much attenuated in a Kv1.2 V370G mutant defective in C-type inactivation. Therefore,
block of Kv1.2 channels by AHR did not appear to involve direct occlusion of the outer pore but depended on C-type inactivation.
AHR could thus be a probe targeting Kv channel C-type inactivation gate. 相似文献
4.
The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid
cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 μM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase.
Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 μM of
either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder
was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of
polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug
treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity
against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.
Received 17 January 2002; received after revision 22 February 2002; accepted 22 February 2002 相似文献
5.
Immunological evidence suggests that plants, like vertebrates, contain natriuretic peptides (NPs) and that rat atrial NP
(rANP) binds specifically to plant membranes and promotes concentration and conformation-dependent stomatal opening. Stomatal
opening and specific increases in cGMP levels were also observed in response to immunoreactive plant NP (irPNP). Here we report
that both 1 μM rANP and irPNP (100 ng total protein/100 μL) significantly increase radial water movements out of the xylem
of shoots of Tradescantia multiflora. Enhanced radial water movements are also observed in response to the cell permeant cGMP analogue 8-Br-cGMP (100 nM). The
water channel inhibitor mercuric chloride (HgCl2) significantly inhibits radial water movements at concentrations of 50 μM, while the presence of 10 μM 2-hydroxyethylmercaptoethanol
(ME) prevents the inhibitory effect of the mercurial. The guanylate cyclase inhibitor LY 83583 at a concentration of 20 μM
and sodium azide (NaN3) at concentrations of ≥ 1 μM both also reduce radial water movements. We therefore conclude that the regulation of radial
water movement out of the xylem involves modulation of cGMP levels, water channels and respiration-dependent processes. In
addition, we propose that NPs have a critical role to play in radial water movements out of the xylem and speculate that as
in vertebrates, NP effects might, at least in part, be mediated via the regulation of guanylate cyclases and water channels.
Received 15 June 1998; received after revision 7 August 1998; accepted 26 August 1998 相似文献
6.
J. Pincemail C. Deby A. Thirion M. de Bruyn-Dister R. Goutier 《Cellular and molecular life sciences : CMLS》1988,44(5):450-453
Summary Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50=3.5 M) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the, MPO/H2O2/Cl– system. 相似文献
7.
R. Shankar M. R. Brown L. K. Wong J. D. Sallis 《Cellular and molecular life sciences : CMLS》1984,40(3):265-267
Summary Phosphocitrate and its analogue N-sulpho-2-amino tricarballylate were compared with ethane-1-hydroxy-1, 1-diphosphonate for inhibition of calcium phosphate crystallization in hydroxyapatite induced crystal growth and45Ca uptake by matrix vesicles. Phosphocitrate (1 M) was the most potent inhibitor followed by ethane-1-hydroxy-1, 1-diphosphonate and N-sulpho-2-amino tricarballylate, the latter requiring a high concentration (100 M) to be equally effective as an inhibitor.Acknowledgments. We wish to thank Mr J. Jordan and Miss L.C. Ward for the excellent technical assistance and Mr R.J. Tennant for the transmission electron microscopy. We also thank the Golden Poultry Farming Industries Ltd., Hobart, Tasmania for their generous supply of broiler strain chickens. 相似文献
8.
J. E. Page S. Madriñán G. H. N. Towers 《Cellular and molecular life sciences : CMLS》1994,50(9):840-842
Bioactivity-directed fractionation of a root extract ofDuroia hirsuta (Rubiaceae), a toxic and potentially allelopathic understory tree from the western Amazon, has led to the isolation of the tetracyclic iridoid lactone, plumericin (1). Bioassays showing plumericin strongly inhibited lettuce radicle elongation at a concentration (IC50) of 35.8 m/ml (123 M). The isolation of a highly potent inhibitor of plant growth fromDuroia hirsuta supports the hypothesis that the lack of vegetation surrounding this tree is the result of allelopathy. 相似文献
9.
Carballar-Lejarazú R Rodríguez MH de la Cruz Hernández-Hernández F Ramos-Castañeda J Possani LD Zurita-Ortega M Reynaud-Garza E Hernández-Rivas R Loukeris T Lycett G Lanz-Mendoza H 《Cellular and molecular life sciences : CMLS》2008,65(19):3081-3092
Scorpine is an antimicrobial peptide whose structure resembles a hybrid between a defensin and a cecropin. It exhibits antibacterial
activity and inhibits the sporogonic development of parasites responsible for murine malaria. In this communication we report
the production of scorpine in a heterelogous system, using a specific vector containing its cloned gene. The recombinantly
expressed scorpine (RScp) in Anopheles gambie cells showed antibacterial activity against Bacillus subtilis and Klebsiella pneumoniae, at 5 and 10 μM, respectively. It also produced 98% mortality in sexual stages of Plasmodium berghei at 15 μM and 100% reduction in Plasmodium falciparum parasitemia at 5 μM. RScp also inhibited virus dengue-2 replication in C6/36 mosquito cells. In addition, we generated viable
and fertile transgenic Drosophila that overexpresses and correctly secretes RScp into the insect hemolymph, suggesting that the generation of transgenic mosquitoes
resistant to different pathogens may be viable.
Received 6 May 2008; received after revision 24 July 2008; accepted 29 July 2008 相似文献
10.
Resveratrol-type oligostilbenes from Iris clarkei antagonize 20-hydroxyecdysone action in the Drosophila melanogaster B(II) cell line 总被引:2,自引:0,他引:2
Bioassay-guided high-performance liquid chromatography analysis of a MeOH extract of Iris clarkei seeds yielded the resveratrol-type oligomeric stilbenes, ampelopsin B and α-viniferin, which antagonize the action of 20-hydroxyecdysone; with a 20-hydroxyecdysone concentration of 50 nM, the ED50 values were 33 μM and 10 μM, respectively. The structures of these compounds were determined by spectroscopic analysis, notably
ultraviolet, liquid secondary ion mass spectrometry and modern one- and two-dimensional nuclear magnetic resonance techniques.
Received 4 November 1999; accepted 13 December 1999 相似文献
11.
Oxidative stress and hypoxia-like injury cause Alzheimer-type molecular abnormalities in central nervous system neurons 总被引:11,自引:0,他引:11
de la Monte SM Neely TR Cannon J Wands JR 《Cellular and molecular life sciences : CMLS》2000,57(10):1471-1481
Neuronal loss and neuritic/cytoskeletal lesions (synaptic disconnection and proliferation of dystrophic neurites) represent
major dementia-associated abnormalities in Alzheimer’s disease (AD). This study examined the role of oxidative stress as a
factor contributing to both the cell death and neuritic degeneration cascades in AD. Primary neuron cultures were treated
with H2O2 (9–90 μM) or desferrioxamine (2–25 μM) for 24 h and then analyzed for viability, mitochondrial mass, mitochondrial function,
and pro-apoptosis and sprouting gene expression. H2O2 treatment causes free-radical injury and desferrioxamine causes hypoxia-type injury without free radical generation. The
H2O2-treated cells exhibited sustained viability but neurite retraction, impaired mitochondrial function, increased levels of
the pro-apoptosis gene product CD95/Fas, reduced expression of N2J1-immunoreactive neuronal thread protein and synaptophysin,
and reduced distribution of mitochondria in neuritic processes. Desferrioxamine treatment resulted in dose-dependent neuronal
loss associated with impaired mitochondrial function, proliferation of neurites, and reduced expression of GAP-43, which has
a role in path-finding during neurite outgrowth. The results suggest that oxidative stress can cause neurodegeneration associated
with enhanced susceptibility to apoptosis due to activation of pro-apoptosis genes, neurite retraction (synaptic disconnection),
and impaired transport of mitochondria to cell processes where they are likely required for synaptic function. In contrast,
hypoxia-type injury causes neuronal loss with proliferation of neurites (sprouting), impaired mitochondrial function, and
reduced expression of molecules required to form and maintain synaptic connections. Since similar abnormalities occur in AD,
both oxidative stress and hypoxic injury can contribute to AD neurodegeneration.
Received 24 May 2000; received after revision 7 July 2000; accepted 27 July 2000 相似文献
12.
O. J. McConnell R. Longley M. Gunasekera 《Cellular and molecular life sciences : CMLS》1992,48(9):891-892
Isometachromin (1), a new sesquiterpene-quinone that is related structurally to metachromin C (2), and the known compounds ilimaquinone (3) and and 5-epi-ilimaquinone (4), were isolated from a deep water sponge in the family Spongiidae; the structure of isometachromin was elucidated by spectral methods. Isometachromin exhibits in vitro cytotoxicity against the human lung cancer cell line A 549 (IC50=2.6 g/ml), but not against P 388 murine leukemia (IC5010 g/ml) and also exhibits antimicrobial activity.This research is Harbor Branch Oceanographic Institution (HBOI) contribution number 911. We thank Drs S. A. Pomponi and M. Kelly-Borges (HBOI) for sponge taxonomy, and Dr P. McCarthy and T. Peterson (HBOI) for antimicrobial data. 相似文献
13.
F. E. Dorer J. M. Stewart J. W. Ryan 《Cellular and molecular life sciences : CMLS》1978,34(11):1436-1436
Summary Arg-Pro-Pro-Gly-Phe, the N-terminal pentapeptide of bradykinin, is not an inhibitor of angiotensin-converting enzyme and is not hydrolyzed by the enzyme. Arg-Pro-Pro, the N-terminal tripeptide is a relatively potent (IC50=2.3×106 M) inhibitor but its higher homolog, Gly-Arg-Met-Lys-Arg-Pro-Pro is not an inhibitor of angiotensin-converting enzyme.This work was supported in part by grants from the US Public Health Service (HL 18415, HL 15691, HL 19764) and the John A. Hartford Foundation, Inc., and by the Medical Research Service of the Veterans Administration. 相似文献
14.
The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently
have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized
by a conserved cysteine knot pattern: C-C-CC-C-C. While ω-conotoxins and κ-conotoxins block Ca2+ and K+ channels, respectively, the closely related δ- and μO-conotoxins affect voltage-gated Na+ channels (Nav channels). δ-conotoxins mainly remove the fast inactivation of Nav channels and, thus, functionally resemble long-chain scorpion α-toxins. μO-conotoxins are functionally similar to μ-conotoxins,
since they inhibit the ion flow through Nav channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms.
Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Nav channels.
Received 27 December 2006; received after revision 30 January 2007; accepted 19 February 2007 相似文献
15.
Nadja Mannowetz Sabine Kartarius Gunther Wennemuth Mathias Montenarh 《Cellular and molecular life sciences : CMLS》2010,67(22):3905-3913
Protein kinase CK2 is an ubiquitously expressed enzyme that is absolutely necessary for the survival of cells. Besides the
holoenzyme consisting of the regulatory β-subunit and the catalytic α- or α′-subunit, the subunits exist in separate forms.
The subunits bind to a number of other cellular proteins. We show the expression of individual subunits as well as interaction
with the transitional nuclear protein TNP1 and with the motor neuron protein KIF5C during spermatogenesis. TNP1 is a newly
identified binding partner of the α-subunit of CK2. CK2α and KIF5C were found in late spermatogenesis, whereas CK2β and TNP1
were found in early spermatogenesis. CK2α, CK2α′, TNP1, and KIF5C were detected in the acrosome of spermatozoa, while CK2β
was detectable in the mid-piece. Combinations of CK2 subunits might determine interactions with other proteins during spermatogenesis.
KIF5C as a kinesin motor neuron protein is probably involved in the redistribution of proteins during spermatogenesis. 相似文献
16.
Y. Takeuchi P. J. Birckbichler M. K. Patterson Jr. 《Cellular and molecular life sciences : CMLS》1995,51(4):339-342
We show that -immunoglobulin (IgG) binds calmodulin (CaM) in a Ca2+-independent manner, with Kd value of (1.7±0.5)×10–7M. A single IgG molecule maximally bound 10 CaM molecules. The binding is to the heavy chain or Fab portion, but not the Fc portion, of the IgG molecules. Ca2+ greatly diminished the interaction between IgG and CaM, with IC50=8–9M. These data give a novel insight into protein-protein interactions. 相似文献
17.
P. C. Braga E. Soldavini A. Pecile V. Sibilia C. Netti 《Cellular and molecular life sciences : CMLS》1996,52(1):60-65
Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 M/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H1 and H2 agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H1 agonist 2-pyridylethylamine (0.4–1.0 M/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H2 agonist dimaprit (0.05–0.2 M/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H1 antagonist, 0.1 M/rat, i.c.v.) nor zolantidine (H2 antagonist, 0.01 M/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 M/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H1 receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus. 相似文献
18.
We report that histones H2A and H2B possess gonadotrophin-releasing activity in vitro and assess the signal transduction
pathways involved in these effects. Perifused and incubated rat anterior pituitary (AP) cells were used, and luteinizing hormone
(LH) and follicle stimulating hormone (FSH) were measured by RIA. Perifusion of cells with histone H2A (30 μM) or histone
H2B (30 μM), markedly stimulated LH release but failed to elicit any FSH response. Cells incubated with 6 or 30 μM histone
H2A showed a dose- and time-dependent stimulatory effect on both LH and FSH release which was blocked by 1 μM peptide MB35,
an 86–120 amino acid fragment of histone H2A. Incubation of pituitary cells with gonadotrophin-releasing hormone (GnRH) and
histones H2A or H2B showed a stimulatory effect on LH and FSH release which was similar to the sum of the separate effects.
Trifluoperazine, as well as ethylene glycol bis(b-aminoethyl ether) N,N,N′,N′-tetraacetic acid (EGTA), alone or in the presence
of the calcium ionophore A23187, significantly reduced the response of AP cells to histones. Various cyclic adenosine monophosphate
(cAMP) enhancers had no effect on histone-stimulated release of gonadotrophins in incubated AP cells. Our results confirm
previous evidence that histones may act as hypophysiotrophic signals. Calcium- and diacylglycerol-associated pathways, but
not cAMP, appear to participate in these effects.
Received 11 August 1997; received after revision 20 January 1998; accepted 26 January 1998 相似文献
19.
J. Schaller U. Kämpfer S. Schürch L. Kuhn-Nentwig S. Haeberli W. Nentwig 《Cellular and molecular life sciences : CMLS》2001,58(10):1538-1545
CSTX-9 (68 residues, 7530.9 Da) is one of the most abundant toxic polypeptides in the venom of the wandering spider Cupiennius salei. The amino acid sequence was determined by Edman degradation using reduced and alkylated CSTX-9 and peptides generated by
cleavages with endoproteinase Asp-N and trypsin, respectively. Sequence comparison with CSTX-1, the most abundant and the
most toxic polypeptide in the crude spider venom, revealed a high degree of similarity (53% identity). By means of limited
proteolysis with immobilised trypsin and RP-HPLC, the cystine-containing peptides of CSTX-9 were isolated and the disulphide
bridges were assigned by amino acid analysis, Edman degradation and nanospray tandem mass spectrometry. The four disulphide
bonds present in CSTX-9 are arranged in the following pattern: 1-4, 2-5, 3-8 and 6-7 (Cys6-Cys21, Cys13-Cys30, Cys20-Cys48, Cys32-Cys46). Sequence comparison of CSTX-1 with CSTX-9 clearly indicates the same disulphide bridge pattern, which is also found in
other spider polypeptide toxins, e.g. agatoxins (ω-AGA-IVA, ω-AGA-IVB, μ-AGA-I and μ-AGA-VI) from Agelenopsis aperta, SNX-325 from Segestria florentina and curtatoxins (CT-I, CT-II and CT-III) from Hololena curta. CSTX-1/CSTX-9 belong to the family of ion channel toxins containing the inhibitor cystine knot structural motif. CSTX-9,
lacking the lysine-rich C-terminal tail of CSTX-1, exhibits a ninefold lower toxicity to Drosophila melanogaster than CSTX-1. This is in accordance with previous observations of CSTX-2a and CSTX-2b, two truncated forms of CSTX-1 which,
like CSTX-9, also lack the C-terminal lysine-rich tail.
Received 23 July 2001; accepted 31 July 2001 相似文献
20.
The sensitivity ofDeleya halophila to oxidative stress caused by hydrogen peroxide (H2O2) was found to vary, depending on the NaCl concentration of the growth medium. Pretreatment of the bacteria at a low concentration of H2O2 (50 M) protected the cells against the lethal effects of higher levels (1–2 mM) of H2O2. Exposure ofD. halophila cells to 50 M H2O2 resulted in the induction of several proteins (hydrogen peroxide-inducible proteins, hips). However, the kinetics of induction, the extent of induction and the number of hips appear to be influenced by the salt concentration of the growth medium. Five of the hips exhibited apparent molecular masses identical to those of five heat shock proteins (hsps). 相似文献