共查询到20条相似文献,搜索用时 31 毫秒
1.
《Cell calcium》2017
It has been shown that 2-APB is a nonspecific modulator of ion channel activity, while most of the channels are inhibited by this compound, there are few examples of channels that are activated by 2-APB. Additionally, it has been shown that, 2-APB leads to a reduction in the luminal endoplasmic reticulum Ca2+ level ([Ca2+]ER) and we have carried out simultaneous recordings of both [Ca2+]i and the [Ca2+]ER in HeLa cell suspensions to assess the mechanism involved in this effect. This approach allowed us to determine that 2-APB induces a reduction in the [Ca2+]ER by activating an ER-resident Ca2+ permeable channel more than by inhibiting the activity of SERCA pumps. Interestingly, this effect of 2-APB of reducing the [Ca2+]ER is auto-limited because depends on a replete ER Ca2+ store; a condition that thapsigargin does not require to decrease the [Ca2+]ER. Additionally, our data indicate that the ER Ca2+ permeable channel activated by 2-APB does not seem to participate in the ER Ca2+ leak revealed by inhibiting SERCA pump with thapsigargin. This work suggests that, prolonged incubations with even low concentrations of 2-APB (5 μM) would lead to the reduction in the [Ca2+]ER that might explain the inhibitory effect of this compound on those signals that require Ca2+ release from the ER store. 相似文献
2.
Construction of a ferritin reactor: an efficient means for trapping various heavy metal ions in flowing seawater 总被引:2,自引:0,他引:2
An apparatus consisting of two pumps, a mixer, a ferritin reactor, and a spectrophotometer was constructed to study the ability to trap various heavy metal ions (M2+) and the dynamics of a reconstituted ferritin reactor in flowing seawater. Reconstituted pig spleen ferritin (PSFr) is assembled from apo-protein shell to form a reconstituted iron core. The main components of the PSFr are its core, which contains an Fe2+:Pi stoichiometry of 6.0±0.5, reconstituted from pig spleen apoferritin (apo PSF), Fe2+, inorganic phosphate (Pi), and O2 (0.6 atm). The Fe3+—Pi clusters within the PSFr core exhibit resistance to salt ranging from 1% to 6% NaCl. The ferritin reactor consists of PSFr and an oscillating bag. Using the reactor, M2+ ions such as Cd2+, Zn2+, Co2+, and Mn2+ are directly trapped by the ferritin. We found a 1:2±0.2 stoichiometry of the trapped M2+ to the released iron as measured by chemical analysis or atomic absorption spectrometry; nontransient elements such as Na+, K+, Ca2+, etc., were scarcely trapped by the reactor. This study provides basic conditions for establishing a ferritin reactor and a convenient means for monitoring the pollution of heavy metal ions in seawater. 相似文献
3.
Hideaki E. Kato Keiichi Inoue Hideki Kandori Osamu Nureki 《BioEssays : news and reviews in molecular, cellular and developmental biology》2016,38(12):1274-1282
4.
Chikashi Toyoshima 《The EMBO journal》2009,28(12):1782-1791
Heavy metal pumps constitute a large subgroup in P‐type ion‐transporting ATPases. One of the outstanding features is that the nucleotide binding N‐domain lacks residues critical for ATP binding in other well‐studied P‐type ATPases. Instead, they possess an HP‐motif and a Gly‐rich sequence in the N‐domain, and their mutations impair ATP binding. Here, we describe 1.85 Å resolution crystal structures of the P‐ and N‐domains of CopA, an archaeal Cu+‐transporting ATPase, with bound nucleotides. These crystal structures show that CopA recognises the adenine ring completely differently from other P‐type ATPases. The crystal structure of the His462Gln mutant, in the HP‐motif, a disease‐causing mutation in human Cu+‐ATPases, shows that the Gln side chain mimics the imidazole ring, but only partially, explaining the reduction in ATPase activity. These crystal structures lead us to propose a role of the His and a mechanism for removing Mg2+ from ATP before phosphoryl transfer. 相似文献
5.
Action of the herbicides neburon and siduron on membrane permeabilities in potato tuber mitochondria
CHRISTIAN GAUVRIT 《Physiologia plantarum》1980,48(3):448-452
The herbicides neburon and siduron are uncouplers of oxidative phosphorylation in potato tuber (Solanum tuberosum L. cv. Bintje) mitochondria. Their effect on the ion permeabilities of the mitochondrial membrane was investigated using the acid-base pulse technique, swelling experiments and integrity tests. Both herbicides permeabilize the membrane to H+ ions. They have no action on the permeabilities of K+ and Fe(CN)3?6. The swelling observed with Ca2+ was better interpreted as an effect on membrane structure than as a true swelling. Diuron, a parent compound that does not uncouple oxidative phosphorylation, does not act on Ca2+-induced apparent swelling. 相似文献
6.
The ATP.Mg-dependent type 1 protein phosphatase is inactive as isolated but can be activated in several different ways. In this report, we show that the phosphatase can also be activated by the Fe2+/ascorbate system. Activation of the phosphatase requires both Fe2+ ion and ascorbate and the level of activation is dependent on the concentrations of Fe2+ ion and ascorbate. In the presence of 20 mM ascorbate, the Fe2+ ion concentrations required for half-maximal and maximal activation are about 0.3 and 3mM, respectively. Several common divalent metal ions, including Co2+, Ni2+, Cu2+, Mg2+, and Ca2+ ions, cannot cooperate with ascorbate to activate the phosphatase, and SH-containing reducing agents such as 2-mercaptoethanol and dithiothreitol cannot cooperate with Fe2+ ion to activate the phosphatase, indicating that activation of the phosphatase by the Fe2+/ascorbate system is a specific process. Moreover, H2O2, a strong oxidizer, could significantly diminish the phosphatase activation by the Fe2+/ascorbate system, suggesting that reduction mechanism other than SH-SS interchange is a prerequisite for the Fe2+/ascorbate-mediated phosphatase activation. Taken together, the present study provides initial evidence for a new mode of type 1 protein phosphatase activation mechanism.Abbreviations MAPK
mitogen-activated protein kinase
- MCO
metal ion-catalyzed oxidation
- kinase FA
the activating factor of ATP.Mg-dependent protein phosphatase
- I2
inhibitor-2
- EDTA
ethylenediaminetetraacetic acid
- MBP
myelin basic protein 相似文献
7.
Richard G. Hansford 《Journal of bioenergetics and biomembranes》1994,26(5):495-508
A model has been proposed in which mitochondrial Ca2+ ion transport serves to regulate mitochondrial matrix free Ca2+ ([Ca2+]m), with the advantage to the animal that this allows the regulation of pyruvate dehydrogenase and the tricarboxylate cycle in response to energy demand. This article examines recent evidence for dehydrogenase activation and for increases in [Ca2+]m in response to increased tissue energy demands, especially in cardiac myocytes and in heart. It critiques recent results on beat-to-beat variation in [Ca2+]m in cardiac muscle and also briefly surveys the impact of mitochondrial Ca2– transport on transient changes in cytosolic free Ca2+ in excitable tissues. Finally, it proposes that a failure to elevate [Ca2+]m sufficiently in response to work load may underlie some cardiomyopathies of metabolic origin. 相似文献
8.
Extracellular potassium concentration, [K+]o, and intracellular calcium, [Ca2+]i, rise during neuron excitation, seizures and spreading depression. Astrocytes probably restrain the rise of K+ in a way that is only partly understood. To examine the effect of glial K+ uptake, we used a model neuron equipped with Na+, K+, Ca2+ and Cl− conductances, ion pumps and ion exchangers, surrounded by interstitial space and glia. The glial membrane was either “passive”,
incorporating only leak channels and an ion exchange pump, or it had rectifying K+ channels. We computed ion fluxes, concentration changes and osmotic volume changes. Increase of [K+]o stimulated the glial uptake by the glial 3Na/2K ion pump. The [K+]o flux through glial leak and rectifier channels was outward as long as the driving potential was outwardly directed, but it
turned inward when rising [K+]o/[K+]i ratio reversed the driving potential. Adjustments of glial membrane parameters influenced the neuronal firing patterns, the
length of paroxysmal afterdischarge and the ignition point of spreading depression. We conclude that voltage gated K+ currents can boost the effectiveness of the glial “potassium buffer” and that this buffer function is important even at moderate
or low levels of excitation, but especially so in pathological states. 相似文献
9.
A new ion sensor based on hybrid SiO2‐coated CdTe nanocrystals (NCs) was prepared and applied for sensitive sensing of Cu2+ and Ag+ for the selective quenching of photoluminescence (PL) of NCs in the presence of ions. As shown by ion detection experiments conducted in pure water rather than buffer solution, PL responses of NCs were linearly proportional to concentrations of Cu2+ and Ag+ ions < 3 and 7 uM, respectively. Much lower detection limits of 42.37 nM for Cu2+ and 39.40 nM for Ag+ were also observed. In addition, the NC quenching mechanism was discussed in terms of the characterization of static and transient optical spectra. The transfer and trapping of photoinduced charges in NCs by surface energy levels of CuS and Ag2S clusters as well as surface defects generated by the exchange of Cu2+ and Ag+ ions with Cd2+ ion in NCs, resulted in PL quenching and other optical spectra changes, including steady‐state absorption and transient PL spectra. It is our hope that these results will be helpful in the future preparation of new ion sensors. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
10.
Active ion uptake and maintenance of cation-anion balance: A critical examination of their role in regulating rhizosphere pH 总被引:11,自引:0,他引:11
R. J. Haynes 《Plant and Soil》1990,126(2):247-264
The processes responsible for maintenance of cation-anion balance in plants and their relation to active ion accumulation and changes in rhizosphere pH are outlined and discussed. The major processes involved are: (1) accumulation and degradation of organic acids which occur in the plant mainly as organic acid anions (and their transfer within the plant) and (2) extrusion of H+ or OH– into the rhizosphere. The relative importance of the two processes is determined by the size of the excess anion or cation uptake. Indeed, plants typically absorb unequal quantities of nutritive cations (NH4
++Ca2++ Mg2++K++Na+) and anions (NO3
–+Cl–+SO4
2–+H2PO4
–) and charge balance is maintained by excretion of an amount of H+ or OH– which is stoichiometrically equal to the respective excess cation or anion uptake. The mechanisms and processes by which H+ and in particular OH– ions are excreted in response to unequal cation-anion uptake are, however, poorly understood.The contemporary view is that primary active extrusion of H+, catalyzed by a membrane-located ATPase, is the major driving force for secondary transport of cations and anions across the plasma membrane. However, the fact that net OH– extrusion often occurs (since excess anion absorption commonly takes place) implies there is a yet-to-be characterized OH– ion efflux mechanism at the plasma membrane that is associated with anion uptake. There is, therefore, a need for future studies of the uptake mechanisms and stoichiometry of anion uptake; particularly that of NO3
– which is often the predominant anion absorbed. Another related phenonenon which requires detailed study in terms of cation-anion balance is localized rhizosphere acidification which can occur in response to deficiencies of Fe and P. 相似文献
11.
Xu Zhang Mengdie Xia Yang Li Huihui Liu Xin Jiang Wenlin Ren Jianping Wu Paul DeCaen Feng Yu Sheng Huang Jianhua He David E Clapham Nieng Yan Haipeng Gong 《Cell research》2013,23(3):409-422
NaChBac is a bacterial voltage-gated sodium (Nav) channel that shows sequence similarity to voltage-gated calcium channels. To understand the ion-permeation mechanism of Nav channels, we combined molecular dynamics simulation, structural biology and electrophysiological approaches to investigate the recently determined structure of NavRh, a marine bacterial NaChBac ortholog. Two Na+ binding sites are identified in the selectivity filter (SF) in our simulations: The extracellular Na+ ion first approaches site 1 constituted by the side groups of Ser181 and Glu183, and then spontaneously arrives at the energetically more favorable site 2 formed by the carbonyl oxygens of Leu179 and Thr178. In contrast, Ca2+ ions are prone to being trapped by Glu183 at site 1, which then blocks the entrance of both Na+ and Ca2+ to the vestibule of the SF. In addition, Na+ permeates through the selective filter in an asymmetrical manner, a feature that resembles that of the mammalian Nav orthologs. The study reported here provides insights into the mechanism of ion selectivity on Na+ over Ca2+ in mammalian Nav channels. 相似文献
12.
Kevin K. W. Wang Basil D. Roufogalis Antonio Villalobo 《The Journal of membrane biology》1989,112(3):233-245
Summary Calpain I purified from human erythrocyte cytosol activates both the ATP hydrolytic activity and the ATP-dependent Ca2+ transport function of the Ca2+-translocating ATPase solubilized and purified from the plasma membrane of human erythrocytes and reconstituted into phosphatidylcholine vesicles. Following partial proteolysis of the enzyme by calpain I, both the initial rates of calcium ion uptake and ATP hydrolysis were increased to near maximal levels similar to those obtained upon addition of calmodulin. The proteolytic activation resulted in the loss of further stimulation of the rates of Ca2+ translocation or ATP hydrolysis by calmodulin as well as an increase of the affinity of the enzyme for calcium ion. However, the mechanistic Ca2+/ATP stoichiometric ratio was not affected by the proteolytic treatment of the reconstituted Ca2+-translocating ATPase. The proteolytic activation of the ATP hydrolytic activity of the reconstituted enzyme could be largely prevented by calmodulin. Different patterns of proteolysis were obtained in the absence or in the presence of calmodulin during calpain treatment: the 136-kDa enzyme was transformed mainly into a 124-kDa active ATPase fragment in the absence of calmodulin, whereas a 127-kDa active ATPase fragment was formed in the presence of calmodulin. This study shows that calpain I irreversibly activates the Ca2+ translocation function of the Ca2+-ATPase in reconstituted proteoliposomes by producing a calmodulin-independent active enzyme fragment, while calmodulin antagonizes this activating effect by protecting the calmodulin-binding domain against proteolytic cleavage by calpain. 相似文献
13.
The dependence of intracellular calcium dynamics on geometrical size relations between calcium-exchanging parts of the intracellular
space was studied in mathematical models corresponding to a thin fragment of the Purkinje neuron spiny dendrite. The plasma
membrane contained ion channels typical of this cell type, including channels that conduct an excitatory synaptic current,
and ion pumps. The model equations took into account calcium exchange between the cytosol, extracellular medium, intracellular
store (a cistern of the endoplasmic reticulum, ER), endogenous calcium buffers, and an exogenous buffer (fluorescent dye used
in the experiments). The ER membrane contained the calcium pump and channels of calcium-dependent and inositol-3-phosphate-dependent
calcium release, as well as leakage channels. With the compartment size fixed, the ER cistern diameter was varied so that
the proportion of the organelle in the total volume changed from 1 to 36%. Under these conditions, identical synaptic excitation
caused similar electrical reactions (calcium spikes) but different concentration responses. Equal increments in the ER diameter
led to unequal, more pronounced at thicker diameters, increments of the peak cytosolic concentrations of Са2+ ([Ca2+]
i
) and of a Са2+-fluorescent dye complex [CaD], as well as those of the Са2+ concentration in the dendrite ER (characterized by a shift from the basal level, Δ[Ca2+]ER). The changes in [Ca2+]
i
and [CaD] followed more adequately those in the volume of the organelle-free cytosol, while Δ[Ca2+]ER changes were more similar to those in the ER membrane area. Therefore, the relative occupancy of the intracellular volume
by organellar calcium stores and their sizes in a dendritic compartment are important structural factors that essentially
modulate the calcium dynamics, and this structural dependence can be adequately reflected in the experiments using fluorophores.
Neirofiziologiya/Neurophysiology, Vol. 41, No. 1, pp. 19–31, January–February, 2009. 相似文献
14.
Tian Yow Tsong 《Journal of biological physics》2002,28(2):309-325
Na,K-ATPase uses chemical bond energy of ATP to pump K+ into, andNa+ out of a cell. Both are uphill transports. During the catalyticcycle the enzyme alternates between two conformational states, E1 andE2. This communication describes an experiment, which employs electricfield to drive oscillation or fluctuation of enzyme conformation betweenthe E1 and the E2 states. It is shown that the field-inducedconformational oscillation or fluctuation leads to uphill pumping of thecation by the enzyme without consumption of ATP. Biochemical specificityof the catalysis is preserved. Data indicate that Na,K-ATPase can harvestenergy from the applied electric field to perform chemical work, and aratchet mechanism is inherent in this energy transduction process. ATheory of Electroconformational Coupling (TEC) that embodies essentialfeatures of the Brownian Ratchet successfully simulates the field-frequencyand field-amplitude optima and other features of the ion pumping activity.A four-state TEC motor can achieve high efficiency of the energytransduction, asymptotically reaching 100% under the optimal condition.Pumping by ion rectification fails to reach high efficiency. The TECconcept is also mused to understand other biological motors and engines. 相似文献
15.
The oxidative burst, the rapid production of O2- and H2O2 by plant cells in response to pathogens and Stressors, is a critical step in plant disease resistance and is controlled by
several different elicitor-initiated signaling pathways. While different defense elicitors appear to activate disparate initial
steps in signaling the oxidative burst, all of the elicitors tested thus far appear to stimulate pathways that converge on
the same three core signaling intermediates: 1) the Ca2+-independent activation of a mitogen-activated protein kinase (MAPK) family member, 2) the influx of Ca2+ into the cytosol, deriving most critically from an internal compartment, and 3) the Ca2+-dependent activation of additional protein kinases including a second MAPK homologue and possibly calcium dependent protein
kinases (CDPKs). Data from several recent reports are summarized to place these signaling events into a complete and updated
model of signaling to the plant oxidative burst. 相似文献
16.
This paper reviews the model of the control of mitochondrial substrate oxidation by Ca2+ ions. The mechanism is the activation by Ca2+ of four mitochondrial dehydrogenases, viz: glycerol 3-phosphate dehydrogenase, the pyruvate dehydrogenase multienzyme complex (PDH), NAD-linked isocitrate dehydrogenase (NAD-IDH) and 2-oxoglutarate dehydrogenase (OGDH). This results in the increase, or near-maintenance, of mitochondrial NADH/NAD ratios in the activated state, depending upon the tissue and the degree of "downstream" activation by Ca2+, likely at the level of the F1F0 ATP-ase. Higher values of the redox span of the respiratory chain allow for greatly increased fluxes through oxidative phosphorylation with a minimal drop in protonmotive force and phosphorylation potential. As PDH, NAD-IDH and OGDH are all located within the inner mitochondrial membrane, it is changes in matrix free Ca2+ ( [Ca2+]m ) which act as a signal to these activities. In this article, we review recent work in which ([Ca2+]m) is measured in cells and tissues, using different techniques, with special emphasis on the question of the degree of damping of ([Ca2+]m) relative to changes in cytosol free Ca2+ in cells with rapid transients in cytosol Ca2+, e.g. cardiac myocytes. Further, we put forward the point of view that the failure of mitochondrial energy transduction to keep pace with cellular energy needs in some forms of heart failure may involve a failure of ([Ca2+]m) to be raised adequately to allow the activation of the dehydrogenases. We present new data to show that this is so in cardiac myocytes isolated from animals suffering from chronic, atreptozocin-induced diabetes. This raises the possibility of therapy based upon partial inhibition of mitochondrial Ca2+ efflux pathways, thereby raising ([Ca2+]m) at a given, time-average value of cytosol free Ca2+. 相似文献
17.
Shiqiang Zhao Christopher D. Sewell Ruiping Liu Songru Jia Zewei Wang Yanjie He Kunjie Yuan Huile Jin Shun Wang Xueqin Liu Zhiqun Lin 《Liver Transplantation》2020,10(6)
Superior reaction reversibility of electrode materials is urgently pursued for improving the energy density and lifespan of batteries. Tin dioxide (SnO2) is a promising anode material for alkali‐ion batteries, having a high theoretical lithium storage capacity of 1494 mAh g? based on the reactions of SnO2 + 4Li+ + 4e? ? Sn + 2Li2O and Sn + 4.4Li+ + 4.4e? ? Li4.4Sn. The coarsening of Sn nanoparticles into large particles induced reaction reversibility degradation has been demonstrated as the essential failure mechanism of SnO2 electrodes. Here, three key strategies for inhibiting Sn coarsening to enhance the reaction reversibility of SnO2 are presented. First, encapsulating SnO2 nanoparticles in physical barriers of carbonaceous materials, conductive polymers or inorganic materials can robustly prevent Sn coarsening among the wrapped SnO2 nanoparticles. Second, constructing hierarchical, porous or hollow structured SnO2 particles with stable void boundaries can hinder Sn coarsening between the void‐divided SnO2 subunits. Third, fabricating SnO2‐based heterogeneous composites consisting of metals, metal oxides or metal sulfides can introduce abundant heterophase interfaces in cycled electrodes that impede Sn coarsening among the isolated SnO2 crystalline domains. Finally, a perspective on the future prospect of the structural/compositional designs of SnO2 as anode of alkali‐ion batteries is highlighted. 相似文献
18.
Amritlal Mandal Sudip DasTapati Chakraborti Pulak KarBiswarup Ghosh Sajal Chakraborti 《Biochimica et Biophysica Acta (BBA)/General Subjects》2006
The properties of Ca2+-ATPase purified and reconstituted from bovine pulmonary artery smooth muscle microsomes {enriched with endoplasmic reticulum (ER)} were studied using the detergents 1,2-diheptanoyl-sn-phosphatidylcholine (DHPC), poly(oxy-ethylene)8-lauryl ether (C12E8) and Triton X-100 as the solubilizing agents. Solubilization with DHPC consistently gave higher yields of purified Ca2+-ATPase with a greater specific activity than solubilization with C12E8 or Triton X-100. DHPC was determined to be superior to C12E8; while that the C12E8 was determined to be better than Triton X-100 in active enzyme yields and specific activity. DHPC solubilized and purified Ca2+-ATPase retained the E1Ca−E1*Ca conformational transition as that observed for native microsomes; whereas the C12E8 and Triton X-100 solubilized preparations did not fully retain this transition. The coupling of Ca2+ transported to ATP hydrolyzed in the DHPC purified enzyme reconstituted in liposomes was similar to that of the native micosomes, whereas that the coupling was much lower for the C12E8 and Triton X-100 purified enzyme reconstituted in liposomes. The specific activity of Ca2+-ATPase reconstituted into dioleoyl-phosphatidylcholine (DOPC) vesicles with DHPC was 2.5-fold and 3-fold greater than that achieved with C12E8 and Triton X-100, respectively. Addition of the protonophore, FCCP caused a marked increase in Ca2+ uptake in the reconstituted proteoliposomes compared with the untreated liposomes. Circular dichroism analysis of the three detergents solubilized and purified enzyme preparations showed that the increased negative ellipticity at 223 nm is well correlated with decreased specific activity. It, therefore, appears that the DHPC purified Ca2+-ATPase retained more organized and native secondary conformation compared to C12E8 and Triton X-100 solubilized and purified preparations. The size distribution of the reconstituted liposomes measured by quasi-elastic light scattering indicated that DHPC preparation has nearly similar size to that of the native microsomal vesicles whereas C12E8 and Triton X-100 preparations have to some extent smaller size. These studies suggest that the Ca2+-ATPase solubilized, purified and reconstituted with DHPC is superior to that obtained with C12E8 and Triton X-100 in many ways, which is suitable for detailed studies on the mechanism of ion transport and the role of protein–lipid interactions in the function of the membrane-bound enzyme. 相似文献
19.
Rivka Goldshleger Guy Patchornik Meirav Bar Shimon Daniel M. Tal Robert L. Post Steven J. D. Karlish 《Journal of bioenergetics and biomembranes》2001,33(5):387-399
This chapter describes contributions of transition metal-catalyzed oxidative cleavage of Na+,K+-ATPase to our understanding of structure–function relations. In the presence of ascorbate/H2O2, specific cleavages are catalyzed by the bound metal and because more than one peptide bond close to the metal can be cleaved, this technique reveals proximity of the different cleavage positions within the native structure. Specific cleavages are catalyzed by Fe2+ bound at the cytoplasmic surface or by complexes of ATP–Fe2+, which directs the Fe2+ to the normal ATP–Mg2+ site. Fe2+- and ATP–Fe2+-catalyzed cleavages reveal large conformation-dependent changes in interactions between cytoplasmic domains, involving conserved cytoplasmic sequences, and a change of ligation of Mg2+ ions between E1P and E2P, which may be crucial in facilitating hydrolysis of E2P. The pattern of domain interactions in E1 and E2 conformations, and role of Mg2+ ions, may be common to all P-type pumps. Specific cleavages can also be catalyzed by Cu2+ ions, bound at the extracellular surfaces, or a hydrophobic Cu2+-diphenyl phenanthroline (DPP) complex, which directs the Cu2+ to the membrane–water interface. Cu2+- or Cu2+-DPP-catalyzed cleavages are providing information on / subunit interactions and spatial organization of transmembrane segments. Transition metal-catalyzed cleavage could be widely used to investigate other P-type pumps and membrane proteins and, especially, ATP binding proteins. 相似文献
20.
To define the molecular mechanism(s) of carvedilol inhibition of lipid peroxidation we have utilized model systems that allow us to study the different reactions involved in this complex process.Carvedilol inhibits the peroxidation of sonicated phosphatidylcholine liposomes triggered by FeCl2 addition whereas atenolol, pindolol and labetalol are ineffective. The inhibition proved not to be ascribable (a) to an effect on Fe2+ autoxidation and thus on the generation of oxygen derived radical initiators; (b) to the scavenging of the inorganic initiators O·-2 and ·OH; (c) to an effect on the reductive cleavage of organic hydroperoxides by FeCl2; (d) to the scavenging of organic initiators. The observations that (a) carvedilol effectiveness is inversely proportional to the concentration of FeCl2 and lipid hydroperoxides in the assay; (b) the drug prevents the onset of lipid peroxidation stimulated by FeCl3 addition and; (c) it can form a complex with Fe3+, suggest a molecular mechanism for carvedilol action. It may inhibit lipid peroxidation by binding the Fe3+ generated during the oxidation of Fe2+ by lipid hydroperoxides in the substrate. The lag time that carvedilol introduces in the peroxidative process would correspond to the time taken for carvedilol to be titrated by Fe3+; when the drug is consumed the Fe3+ accumulates to reach the critical parameter that stimulates peroxidation. According to this molecular mechanism the antioxidant potency of carvedilol can be ascribed to its ability to bind a species, Fe3+, that is a catalyst of the process and to its lipophilic nature that concentrates it in the membranes where Fe3+ is generated by a site specific mechanism. 相似文献