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1.
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
2.
V. J. Csernus T. Hammer D. Peschke E. Peschke 《Cellular and molecular life sciences : CMLS》1998,54(7):733-743
Insulin secretion from isolated pancreatic islets of 8- to 12-day-old rats was investigated in a dynamic in vitro (perifusion)
system. The aims of the study were (i) to describe a carefully controlled in vitro method to study the mechanism of insulin
secretion and to analyse the effects and dynamic interactions of bioactive compounds on isolated rat pancreatic islets, (ii)
to validate the method by comparing fundamental data on the functions of the islets obtained with this method to those collected
with other techniques; and (iii) to find novel features of the control of insulin secretion. The method was carefully designed
to maintain the functional capacity of the explanted cells. A functional standardization system was elaborated consisting
of (i) analysis of the changes in the basal hormone secretion of the cells; (ii) evaluating responses to a standard, specific
stimuli (50 mM glucose for 3 min); (iii) determining the alteration of the momentary size of the hormone pool with responses
to KCl; and (iv) direct determination of the total intracellular hormone content from the extract of the column. The technique
provides accurate quantitative data on the dynamic responses to biologically active compounds that act directly on the pancreatic
islets. The islets maintained their full responsiveness for up to 7 days, and responses as close as in 1-min intervals could
be distinguished. A linear dose-response relationship was found on the glucose-induced insulin release in case of 3-min stimulation
with 4 and 500 mM of glucose (lin-log graph). Utilizing this method, we showed that no desensitization to glucose-induced
insulin release can be observed if the responsiveness of the cells is properly maintained and the parameters of the stimulation
are carefully designed. Exposure of the explanted islets to 10 μM acetylcholine or 30 mM arginine (Arg) induced a transitory
elevation of insulin release similar in shape to that experienced after glucose stimulation. Norepinephrine (NE), dopamine
(DA) and somatostatin (SS) did not induce any detectable alteration on the basal insulin secretion of the islets. However,
100 nM SS given together with 50 mM glucose, 30 mM Arg or 10 μM acetylcholine significantly reduced the insulin-releasing
effect of these substances (by 75.5, 71.5 and 72.5%, respectively). At the same time, SS did not alter the insulin response
of the islets to 100 mM elevation of K+ concentration. SS also inhibited glucose-induced insulin release in a dose-dependent way (ED50 = 22 nM). A similar dose-dependent inhibitory effect on glucose-induced insulin release was found with NE (ED50 = 89 nM) and DA (ED50 = 2.2 μM). γ-Aminobutyric acid (GABA) did not influence insulin release under similar circumstances.
Received 16 January 1998; received after revision 6 May 1998; accepted 8 May 1998 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.
G. Meyer G. Bottà G. Fedele D. Cremaschi 《Cellular and molecular life sciences : CMLS》1995,51(11):1045-1051
In intact tissue, [d-Ala2,MePhe4, Gly-ol5] enkephalin (10–5 M;-ligand), diminsihed short-circuit current (Isc) and increased water, Na+ and Cl– net fluxes in vitro under open circuit conditions; it also inhibitedL-valine absorption andL-valine-dependent variations of short-circuit current (Isc, val). Naloxone (10–6 M) antagonized these effects. In the absence of the muscularis and myenteric plexus this enkephalin or morphine (-ligand) reduced Isc and Isc, val. These enkephalin effects occurred at different times. Different concentrations of enkephalin were tested for their effects on Isc, val. [d-Ala2,d-Leu5] enkephalin (mainly a -ligand) significantly decreased Isc but not Isc, val. The reduction ofL-valine absorption does not depend on the effects on basal ion transport. Interaction of opioids with-receptors located in the submucosal plexus and/or in the epithelial cell accounts for this reduction. This enkephalin effect seems to be at least partially under the control of the myenteric plexus. 相似文献
5.
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
6.
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
7.
Peschke E Ebelt H Brömme HJ Peschke D 《Cellular and molecular life sciences : CMLS》2000,57(1):158-164
This study compares functional and morphological alterations caused by application of alloxan, streptozotocin, xanthine oxidase/hypoxanthine
(generation of reactive oxygen species), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, liberation of nitric oxide) to isolated
rat pancreatic islets in vitro. In perifusion experiments, membrane leakage—detected by non-stimulated insulin release—was
found after application of all drugs, but showed a substance-specific time pattern. Twenty-four hours after application of
the classical diabetogens (alloxan or streptozotocin), potassium chloride- and glucose-stimulated insulin secretion were markedly
reduced, while a persistent reduction was observed neither after exposure to xanthine oxidase/hypoxanthine, nor to SNAP. Morphological
analysis of the islets revealed that nearly all β-cells were destroyed following alloxan or streptozotocin treatment, while the majority of β-cells were configured regularly after application of xanthine oxidase/hypoxanthine or SNAP. Necrotic cells found after xanthine
oxidase/hypoxanthine usually differed in morphology from those observed after application of the classical diabetogens. While
the former cells were characterised by swollen nuclei, the latter had shrunken nuclei with irregular condensed chromatin.
Apoptosis was found only following nitric oxide exposure. Due to these differences, it seems unlikely that alloxan, streptozotocin,
xanthine oxidase/hypoxanthine, and nitric oxide have a common major feature in their toxic action.
Received 16 September 1999; received after revision 15 November 1999; accepted 26 November 1999 相似文献
8.
Sarno S Mazzorana M Traynor R Ruzzene M Cozza G Pagano MA Meggio F Zagotto G Battistutta R Pinna LA 《Cellular and molecular life sciences : CMLS》2012,69(3):449-460
8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of
protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter
as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as
“denitro NBC”, dNBC), the inhibitory power toward CK2 is almost entirely lost (IC50 > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases
that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC50 values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent
inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural
features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit
of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68
and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved
water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to
the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A
by dNBC. 相似文献
9.
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
10.
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
11.
Porcelli AM Ghelli A Mastrocola T Rugolo M 《Cellular and molecular life sciences : CMLS》1999,56(1-2):167-173
The Ca2+ ionophore ionomycin induced cytosolic [Ca2+]i elevation as well as strong activation of Cl− efflux in mouse mammary epithelial cell lines expressing wild-type or mutated (deletion of phenylalaline 508) cystic fibrosis
transmembrane conductance regulator (CFTR) or vector. Ionomycin-induced Cl− efflux was abolished by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, whereas both activators and inhibitors of phospholipase A2 had no effect, indicating the involvement of Ca2+-dependent Cl- channels. Stimulation of arachidonic acid release by ionomycin and phorbol ester was not significantly different between
wild-type or mutated cell lines, whereas vector-transfected cells exhibited a significant higher release, which was shown
to be due to larger amount of immunoreactive cytosolic phospholipase A2. These results indicate that phospholipase A2 activity of C127 cells was not influenced by the presence of wild-type or mutated CFTR.
Received 27 April 1999; received after revision 11 June 1999; accepted 23 July 1999 相似文献
12.
The chirality of l-/dl-leucine (50–50%) cooligomerization was investigated in liquid and frozen aqueous solutions. Cooligomerization was carried
out by carbonyldiimidazole activation without initiator at an ambient (+22°C) and frozen (−18°C) temperature, respectively.
The separated samples obtained after different time intervals of treatment were completely hydrolyzed (HCl) and the diastereomeric
l- and d-leucine derivates of Marfey's reagent (1-fluoro-2,4-dinitrophenyl-5-l-alanine amide) were then traced and evaluated by RP-HPLC analysis. After 9 days of oligomerization, the l-Leu content was slightly enhanced in the liquid (57%) and somewhat more enhanced in the frozen (64%) samples. After 17 days,
however, the l-Leu content had decreased in the liquid (53%) and frozen (56%) conditions. These l-enantiomer amplifications indicate that an l-antipode is preferentially incorporated into the α-helical turn of the oligomer in the earlier stage of cooligomerization, while, later, the d-antipode is also incorporated. The role of ice in the improved stereoselection is discussed. This is the first recorded example
of the effect of freezing on stereoselection.
Received 27 October 2000; revised 11 December 2000; accepted 4 January 2000 相似文献
13.
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
14.
The uptake ofL-arginine into purified rat brain synaptosomes was investigated with respect to time and various concentrations ofL-[3H] arginine. Specific uptake was found to be linear with time for up to 5 min of incubation at 37°C. Electrolytes, including sodium chloride, potassium chloride, magnesium chloride and calcium chloride, inhibited uptake of 3 ML-arginine, and the inhibitory effect increased with increased electrolyte concentration under constant osmolarity. It was found thatL-arginine was transported into synaptosomes by two uptake components — a high affinity component (3.5 M) and a low affinity component (100 M). These two components were similar to the Ly+ system because of their extreme sensitivity to inhibition byL-lysine andL-ornithine but were distinguishable from each other by kinetic analysis of the uptake data and by their relative sensitivity to inhibition by several amino acids. 相似文献
15.
Summary Using metal-ion buffers it was possible to remove Zn2+, Mg2+ and Mn2+ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are KEMg:4·10–7
M, KEMn:4·10–8
M and KEZn:8·10–13
M (22°C, pH:9.6, :0.07).Acknowledgement: The authors thank Dr.H. U. Wolf for helpful suggestions and valuable discussion and MissH. Köth for technical assistance. 相似文献
16.
Sushma Srivastava K. B. Mathur M. M. Dhar 《Cellular and molecular life sciences : CMLS》1970,26(1):11-12
Zusammenfassung Synthetische Copolymere aus Glutaminsäure und Phenylalanin zeigen Lysozymaktivität. Mit einem Produkt Phe90Glu10 wurde ca. ein Drittel der Lysozymaktivität erreicht.
Communication No. 1415 from the Central Drug Research Institute. Part II — V. K.Naithani, K. B.Mathur and M. M.Dhar, Indian J. Biochem.6, 10 (1969).
To whom enquiries may be made. 相似文献
Communication No. 1415 from the Central Drug Research Institute. Part II — V. K.Naithani, K. B.Mathur and M. M.Dhar, Indian J. Biochem.6, 10 (1969).
To whom enquiries may be made. 相似文献
17.
B. Lanzrein V. Gentinetta H. Abegglen F. C. Baker C. A. Miller D. A. Schooley 《Cellular and molecular life sciences : CMLS》1985,41(7):913-917
Summary Titers of ecdysone, 20-hydroxyecdysone and juvenile hormone III were measured in whole body extracts or hemolymph of embryos, first, penultimate and last stadium nymphs, and adult females ofNaupoheta cinerea. We used a gas-chromatography/mass spectrometry method for quantifying juvenile hormone and a radio-immunoassay for ecdysteroid determination. Juvenile hormone III is particularly abundant in the embryonic stage (up to 960 ng/g), at a low level in first and penultimate stadium nymphs (2–10 ng/ml) and almost absent in the last nymphal stadium; in the adult female the juvenile hormone titer rises to 180 ng/ml in hemolymph during rapid oocyte growth. The titers of ecdysone and 20-hydroxyecdysone undergo similar fluctuations in the embryonic and nymphal stages, being highest at the time of cuticle formation in the embryo and a few days before the nymphal and adult molts (around 100–200 ng/ml for exdysone and 2–4 g/ml for 20-hydroxyecdysone).Acknowledgments. We thank Mrs A. Tschan for rearing the cockroaches, Mr M. Kaltenrieder for drawing the graphs, Mr G.C. Jamieson and Mrs C. Reuter for GC/MS analyses. We are also grateful to the Swiss National Science Foundation (grant no. 3.291-0.82 to B. Lanzrein) and the United States National Science Foundation (grant no. PCM 82-08665 to D.A. Schooley) for their financial support. 相似文献
18.
4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease 总被引:3,自引:0,他引:3
Shringarpure R Grune T Sitte N Davies KJ 《Cellular and molecular life sciences : CMLS》2000,57(12):1802-1809
The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s
disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data
do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins
in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated
that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins.
Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by
the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized
that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ
1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H2O2 modification of Aβ
1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ
1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized
protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s
disease
Received 26 September 2000; accepted 26 September 2000 相似文献
19.
Ligand recognition by the I domain-containing integrins 总被引:11,自引:0,他引:11
Seven of the integrin α subunits described to date, α
1 , α
2 , α
L , α
X , α
d , α
M and α
E , contain a highly conserved I (or A) domain of approximately 200 amino acid residues inserted near the amino-terminus of
the subunit. As the result of a variety of independent experimental approaches, a large body of data has recently accumulated
that indicates that the I domains are independent, autonomously folding domains capable of directly binding ligands that play
a necessary and important role in ligand binding by the intact integrins. Recent crystallographic studies have elucidated
the structures of recombinant α
M and α
L I domains and also delineated a novel divalent cation-binding motif within the I domains (metal ion-dependent adhesion site,
MIDAS) that appears to mediate the divalent cation binding of the I domains and the I domain-containing integrins to their
ligands. 相似文献
20.
Summary The placentae of 17 to 19 days pregnant mice respond to subcutaneous serotonin (15 mg/kg) with vascular changes which lead to the death of the fetuses in 3–4 h. Pretreatment of the females withd-lysergic acid derivatives preserves the life of the young. Thus, LSD showed an ED50 of only 30 g/kg, while UML (Deseril®) gave an ED50 of 3.7 g/kg. PML takes an intermediate position. At a 50% efficiency level, UML (Deseril®) antagonises the effect of a 4000 times higher dose of serotonin. 相似文献