共查询到20条相似文献,搜索用时 296 毫秒
1.
Alhondra Solares-Pérez Jorge A. Sánchez Alejandro Zentella-Dehesa María C. García Ramón M. Coral-Vázquez 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
δ-Sarcoglycan (δ-SG) knockout (KO) mice develop skeletal muscle histopathological alterations similar to those in humans with limb muscular dystrophy. Membrane fragility and increased Ca2+ permeability have been linked to muscle degeneration. However, little is known about the mechanisms by which genetic defects lead to disease.Methods
Isolated skeletal muscle fibers of wild-type and δ-SG KO mice were used to investigate whether the absence of δ-SG alters the increase in intracellular Ca2+ during single twitches and tetani or during repeated stimulation. Immunolabeling, electrical field stimulation and Ca2+ transient recording techniques with fluorescent indicators were used.Results
Ca2+ transients during single twitches and tetani generated by muscle fibers of δ-SG KO mice are similar to those of wild-type mice, but their amplitude is greatly decreased during protracted stimulation in KO compared to wild-type fibers. This impairment is independent of extracellular Ca2+ and is mimicked in wild-type fibers by blocking store-operated calcium channels with 2-aminoethoxydiphenyl borate (2-APB). Also, immunolabeling indicates the localization of a δ-SG isoform in the sarcoplasmic reticulum of the isolated skeletal muscle fibers of wild-type animals, which may be related to the functional differences between wild-type and KO muscles.Conclusions
δ-SG has a role in calcium homeostasis in skeletal muscle fibers.General significance
These results support a possible role of δ-SG on calcium homeostasis. The alterations caused by the absence of δ-SG may be related to the pathogenesis of muscular dystrophy. 相似文献2.
Toshitaka Ikehara Hirotaka Nishisako Yuki Minami Hiromi Ichinose Tairo Shiraishi Mitsuo Kitamura Masayuki Shono Hitoshi Houchi Kazuyoshi Kawazoe Kazuo Minakuchi Kazuo Yoshizaki Yohsuke Kinouchi Hiroshi Miyamoto 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
It has been reported that exposure to electromagnetic fields influences intracellular signal transduction. We studied the effects of exposure to a time-varying 1.5 T magnetic field on membrane properties, membrane cation transport and intracellular Ca2+ mobilization in relation to signals. We also studied the mechanism of the effect of exposure to the magnetic field on intracellular Ca2+ release from Ca2+ stores in adrenal chromaffin cells.Methods
We measured the physiological functions of ER, actin protein, and mitochondria with respect to a neurotransmitter-induced increase in Ca2+ in chromaffin cells exposed to the time-varying 1.5 T magnetic field for 2 h.Results
Exposure to the magnetic field significantly reduced the increase in [Ca2+]i. The exposure depolarized the mitochondria membrane and lowered oxygen uptake, but did not reduce the intracellular ATP content. Magnetic field-exposure caused a morphological change in intracellular F-actin. F-actin in exposed cells seemed to be less dense than in control cells, but the decrease was smaller than that in cytochalasin D-treated cells. The increase in G-actin (i.e., the decrease in F-actin) due to exposure was recovered by jasplakinolide, but inhibition of Ca2+ release by the exposure was unaffected.Conclusions and general significance
These results suggest that the magnetic field-exposure influenced both the ER and mitochondria, but the inhibition of Ca2+ release from ER was not due to mitochondria inhibition. The effect of eddy currents induced in the culture medium may indirectly influence intracellular actin and suppress the transient increase in [Ca2+]i. 相似文献3.
Catalina Carrasco-Pozo Edgar Pastene Carola Vergara Moises Zapata Cristian Sandoval Martin Gotteland 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
The effect of indomethacin (INDO) on Ca2 + mobilization, cytotoxicity, apoptosis and caspase activation and the potential protective effect of quercetin (QUE), resveratrol (RES) and rutin (RUT) were determined in Caco-2 cells.Methods
Caco-2 cells were incubated with INDO in the presence or absence of QUE, RES or RUT. The concentrations of Ca2 + in the cytosol (Fluo-3 AM) and mitochondria (Rhod-2 AM) were determined as well as the cytotoxicity (MTT reduction and LDH leakage), apoptosis (TUNEL) and caspase-3 and 9 activities.Results
INDO promoted Ca2 + efflux from the endoplasmic reticulum (ER), resulting in an early, but transient, increment of cytosolic Ca2 + at 3.5 min, followed by a subsequent increment of intra-mitochondrial Ca2 + at 24 min. INDO also induced cytotoxicity, apoptosis, and increased caspase activities and cytochrome c release. All these alterations were prevented by the inhibitors of the IP3R and RyR receptors, 2-Aminoethoxydiphenyl borate (2-APB) and dantrolene. QUE was the most efficient polyphenol in preventing Ca2 + mobilization induced by INDO and all of its consequences including cytotoxicity and apoptosis.Conclusions
In Caco-2 cells, INDO stimulates ER Ca2 + mobilization, probably through the activation of IP3R and RyR receptors, and the subsequent entry of Ca2 + into the mitochondria. Polyphenols protected the cells against the Ca2 + mobilization induced by INDO and its consequences on cytotoxicity and apoptosis.General significance
These results confirm the possibility of using polyphenols and particularly QUE for the protection of the gastroduodenal mucosa in subjects consuming NSAIDs. 相似文献4.
Background
Calcium (Ca2 +) oscillations are ubiquitous signals present in all cells that provide efficient means to transmit intracellular biological information. Either spontaneously or upon receptor ligand binding, the otherwise stable cytosolic Ca2 + concentration starts to oscillate. The resulting specific oscillatory pattern is interpreted by intracellular downstream effectors that subsequently activate different cellular processes. This signal transduction can occur through frequency modulation (FM) or amplitude modulation (AM), much similar to a radio signal. The decoding of the oscillatory signal is typically performed by enzymes with multiple Ca2 + binding residues that diversely can regulate its total phosphorylation, thereby activating cellular program. To date, NFAT, NF-κB, CaMKII, MAPK and calpain have been reported to have frequency decoding properties.Scope of review
The basic principles and recent discoveries reporting frequency decoding of FM Ca2 + oscillations are reviewed here.Major conclusions
A limited number of cellular frequency decoding molecules of Ca2 + oscillations have yet been reported. Interestingly, their responsiveness to Ca2 + oscillatory frequencies shows little overlap, suggesting their specific roles in cells.General significance
Frequency modulation of Ca2 + oscillations provides an efficient means to differentiate biological responses in the cell, both in health and in disease. Thus, it is crucial to identify and characterize all cellular frequency decoding molecules to understand how cells control important cell programs. 相似文献5.
6.
Ana Paula Zanatta Leila Zanatta Renata Gonçalves Ariane Zamoner Fátima Regina Mena Barreto Silva 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
The secretory activity of Sertoli cells (SC) is dependent on ion channel functions and protein synthesis and is critical to ongoing spermatogenesis. The aim of this study was to investigate the mechanism of action associated with a non-metabolizable amino acid [14C]-MeAIB (α-(methyl-amino)isobutyric acid) accumulation stimulated by T4 and the role of the integrin receptor in this event, and also to clarify whether the T4 effect on MeAIB accumulation and on Ca2+ influx culminates in cell secretion.Methods
We have studied the rapid and plasma membrane initiated effects of T4 by using 45Ca2+ uptake and [45C]-MeAIB accumulation assays, respectively. Thymidine incorporation into DNA was used to monitor nuclear activity and quinacrine to analyze the secretory activity on SC.Results
The stimulation of MeAIB accumulation by T4 appears to be mediated by the integrin receptor in the plasma membrane since tetrac and RGD peptide were able to nullify the effect of this hormone. In addition, T4 increases extracellular Ca2+ uptake and Ca2+ from intracellular stocks to enhance nuclear activity, but this genomic action seems not to influence SC secretion mediated by T4. Also, the cytoskeleton and ClC-3 chloride channel contribute to the membrane-associated responses of SC.Conclusions
T4 integrin receptor activation ultimately determines the plasma membrane responses on amino acid transport in SC, but it is not involved in calcium influx, cell secretion or the nuclear effect of the hormone.General significance
The integrin receptor activation by T4 may take a role in plasma membrane processes involved in the male reproductive system. 相似文献7.
Santosh Kumar Sahu Gopala Krishna Aradhyam Sathyanarayana N. Gummadi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009
Background
Phospholipid scramblases are a group of four homologous proteins conserved from C. elegans to human. In human, two members of the scramblase family, hPLSCR1 and hPLSCR3 are known to bring about Ca2+ dependent translocation of phosphatidylserine and cardiolipin respectively during apoptotic processes. However, affinities of Ca2+/Mg2+ binding to human scramblases and conformational changes taking place in them remains unknown.Methods
In the present study, we analyzed the Ca2+ and Mg2+ binding to the calcium binding motifs of hPLSCR1–4 and hPLSCR1 by spectroscopic methods and isothermal titration calorimetry.Results
The results in this study show that (i) affinities of the peptides are in the order hPLSCR1 > hPLSCR3 > hPLSCR2 > hPLSCR4 for Ca2+ and in the order hPLSCR1 > hPLSCR2 > hPLSCR3 > hPLSCR4 for Mg2+, (ii) binding of ions brings about conformational change in the secondary structure of the peptides. The affinity of Ca2+ and Mg2+ binding to protein hPLSCR1 was similar to that of the peptide I. A sequence comparison shows the existence of scramblase-like motifs among other protein families.Conclusions
Based on the above results, we hypothesize that the Ca2+ binding motif of hPLSCR1 is a novel type of Ca2+ binding motif.General significance
Our findings will be relevant in understanding the calcium dependent scrambling activity of hPLSCRs and their biological function. 相似文献8.
Ruyuan Deng Aifang Nie Fangfang Jian Yun Liu Hongju Tang Juan Zhang Yuqing Zhang Li Shao Fengying Li Libin Zhou Xiao Wang Guang Ning 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
It has been recognized that insulin hypersecretion can lead to the development of insulin resistance and type 2 diabetes mellitus. There is substantial evidence demonstrating that thiazolidinediones are able to delay and prevent the progression of pancreatic β-cell dysfunction. However, the mechanism underlying the protective effect of thiazolidinediones on β-cell function remains elusive.Methods
We synchronously detected the effects of troglitazone on insulin secretion and AMP-activated protein kinase (AMPK) activity under various conditions in isolated rat islets and MIN6 cells.Results
Long-term exposure to high glucose stimulated insulin hypersecretion and inhibited AMPK activity in rat islets. Troglitazone-suppressed insulin hypersecretion was closely related to the activation of AMPK. This action was most prominent at the moderate concentration of glucose. Glucose-stimulated insulin secretion was decreased by long-term troglitazone treatment, but significantly increased after the drug withdrawal. Compound C, an AMPK inhibitor, reversed troglitazone-suppressed insulin secretion in MIN6 cells and rat islets. Knockdown of AMPKα2 showed a similar result. In MIN6 cells, troglitazone blocked high glucose-closed ATP-sensitive K+ (KATP) channel and decreased membrane potential, along with increased voltage-dependent potassium channel currents. Troglitazone suppressed intracellular Ca2 + response to high glucose, which was abolished by treatment with compound C.Conclusion
Our results suggest that troglitazone provides β-cell “a rest” through activating AMPK and inhibiting insulin hypersecretion, and thus restores its response to glucose.General significance
These data support that AMPK activation may be an important mechanism for thiazolidinediones preserving β-cell function. 相似文献9.
Background
In recent years, as our understanding of the various roles played by Ca2 + signaling in development and differentiation has expanded, the challenge of imaging Ca2 + dynamics within living cells, tissues, and whole animal systems has been extended to include specific signaling activity in organelles and non-membrane bound sub-cellular domains.Scope of review
In this review we outline how recent advances in genetics and molecular biology have contributed to improving and developing current bioluminescence-based Ca2 + imaging techniques. Reporters can now be targeted to specific cell types, or indeed organelles or domains within a particular cell.Major conclusions
These advances have contributed to our current understanding of the specificity and heterogeneity of developmental Ca2 + signaling. The improvement in the spatial resolution that results from specifically targeting a Ca2 + reporter has helped to reveal how a ubiquitous signaling messenger like Ca2 + can regulate coincidental but different signaling events within an individual cell; a Ca2 + signaling paradox that until now has been hard to explain.General significance
Techniques used to target specific reporters via genetic means will have applications beyond those of the Ca2 + signaling field, and these will, therefore, make a significant contribution in extending our understanding of the signaling networks that regulate animal development. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signalling. 相似文献10.
Lisandro Lungato Marcos L. Gazarini Edgar J. Paredes-Gamero Ivarne l.S. Tersariol Sergio Tufik Vânia D'Almeida 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Sleep is a physiological event that directly influences health by affecting the immune system, in which calcium (Ca2 +) plays a critical signaling role. We performed live cell measurements of cytosolic Ca2 + mobilization to understand the changes in Ca2 + signaling that occur in splenic immune cells after various periods of sleep deprivation (SD).Methods
Adult male mice were subjected to sleep deprivation by platform technique for different periods (from 12 to 72 h) and Ca2 + intracellular fluctuations were evaluated in splenocytes by confocal microscopy. We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca2 + mobilization in endoplasmic reticulum and mitochondria. Additionally, Ca2 + channel gene expression was evaluatedResults
Splenocytes showed a progressive loss of intracellular Ca2 + maintenance from endoplasmic reticulum (ER) stores. Transient Ca2 + buffering by the mitochondria was further compromised. These findings were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca2 + channels.Conclusions and general significance
These novel data suggest that SD impairs Ca2 + signaling, most likely as a result of ER stress, leading to an insufficient Ca2 + supply for signaling events. Our results support the previously described immunosuppressive effects of sleep loss and provide additional information on the cellular and molecular mechanisms involved in sleep function. 相似文献11.
Natalia DionisioLetizia Albarrán José J. LópezAlejandro Berna-Erro Ginés M. SalidoRégis Bobe Juan A. Rosado 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(8):1483-1494
Background
A novel family of intracellular Ca2+-release channels termed two-pore channels (TPCs) has been presented as the receptors of NAADP (nicotinic acid adenine dinucleotide phosphate), the most potent Ca2+ mobilizing intracellular messenger. TPCs have been shown to be exclusively localized to the endolysosomal system mediating NAADP-evoked Ca2+ release from the acidic compartments.Objectives
The present study is aimed to investigate NAADP-mediated Ca2+ release from intracellular stores in the megakaryoblastic cell line MEG01.Methods
Changes in cytosolic and intraluminal free Ca2+ concentrations were registered by fluorimetry using fura-2 and fura-ff, respectively; TPC expression was detected by PCR.Results
Treatment of MEG01 cells with the H+/K+ ionophore nigericin or the V-type H+-ATPase selective inhibitor bafilomycin A1 revealed the presence of acidic Ca2+ stores in these cells, sensitive to the SERCA inhibitor 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ). NAADP releases Ca2+ from acidic lysosomal-like Ca2+ stores in MEG01 cells probably mediated by the activation of TPC1 and TPC2 as demonstrated by TPC1 and TPC2 expression silencing and overexpression. Ca2+ efflux from the acidic lysosomal-like Ca2+ stores or the endoplasmic reticulum (ER) results in ryanodine-sensitive activation of Ca2+-induced Ca2+ release (CICR) from the complementary Ca2+ compartment.Conclusion
Our results show for the first time NAADP-evoked Ca2+ release from acidic compartments through the activation of TPC1 and TPC2, and CICR, in a megakaryoblastic cell line. 相似文献12.
Lee Hedden Cyril H. Benes Stephen P. Soltoff 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
The activation of various P2 receptors (P2R) by extracellular nucleotides promotes diverse cellular events, including the stimulation of cell signaling protein and increases in [Ca2+]i. We report that some agents that can block P2X7R receptors also promote diverse P2X7R-independent effects on cell signaling.Methods
We exposed native rat parotid acinar cells, salivary gland cell lines (Par-C10, HSY, HSG), and PC12 cells to suramin, DIDS (4,4′-diisothiocyano stilbene-2,2′-disulfonic acid), Cibacron Blue 3GA, Brilliant Blue G, and the P2X7R-selective antagonist A438079, and examined the activation/phosphorylation of ERK1/2, PKCδ, Src, CDCP1, and other signaling proteins.Results
With the exception of suramin, these agents blocked the phosphorylation of ERK1/2 by BzATP in rat parotid acinar cells; but higher concentrations of suramin blocked ATP-stimulated 45Ca2+ entry. Aside from A438079, these agents increased the phosphorylation of ERK1/2, Src, PKCδ, and other proteins (including Dok-1) within minutes in an agent- and cell type-specific manner in the absence of a P2X7R ligand. The stimulatory effect of these compounds on the tyrosine phosphorylation of CDCP1 and its Src-dependent association with PKCδ was blocked by knockdown of CDCP1, which also blocked Src and PKCδ phosphorylation.Conclusions
Several agents used as P2X7R blockers promote the activation of various signaling proteins and thereby act more like receptor agonists than antagonists.General significance
Some compounds used to block P2 receptors have complicated effects that may confound their use in blocking receptor activation and other biological processes for which they are employed, including their use as blockers of various ion transport proteins. 相似文献13.
Background
It has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca2+ oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca2+ oscillations.Methods
The effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca2+ signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy.Results
All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca2+ oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca2+ oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca2+ oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca2+ stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca2+ available to stimulate contraction because an elevation of intracellular Ca2+ concentration induced by exposure to a Ca2+ ionophore (ionomycin) or by photolysis of caged-Ca2+ did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca2+-activated K+ channels, which would be expected to increase Ca2+ influx and contraction. By contrast, the photolysis of caged-IP3 in the presence of agonist, to further elevate the intracellular IP3 concentration, reversed the slowing of the frequency of the Ca2+ oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP3R to IP3 was reduced by FSK and this was supported by the reduced ability of IP3 to release Ca2+ in SMCs in the presence of FSK.Conclusion
These results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca2+ oscillation frequency by reducing internal Ca2+ release through IP3 receptors.14.
Ana M. Rossi Stephen C. ToveyTaufiq Rahman David L. ProleColin W. Taylor 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Inositol 1,4,5-trisphosphate receptors (IP3R) are expressed in almost all animal cells. Three mammalian genes encode closely related IP3R subunits, which assemble into homo- or hetero-tetramers to form intracellular Ca2 + channels.Scope of the review
In this brief review, we first consider a variety of complementary methods that allow the links between IP3 binding and channel gating to be defined. How does IP3 binding to the IP3-binding core in each IP3R subunit cause opening of a cation-selective pore formed by residues towards the C-terminal? We then describe methods that allow IP3, Ca2 + signals and IP3R mobility to be examined in intact cells. A final section briefly considers genetic analyses of IP3R signalling.Major conclusions
All IP3R are regulated by both IP3 and Ca2 +. This allows them to initiate and regeneratively propagate intracellular Ca2 + signals. The elementary Ca2 + release events evoked by IP3 in intact cells are mediated by very small numbers of active IP3R and the Ca2 +-mediated interactions between them. The spatial organization of these Ca2 + signals and their stochastic dependence on so few IP3Rs highlight the need for methods that allow the spatial organization of IP3R signalling to be addressed with single-molecule resolution.General significance
A variety of complementary methods provide insight into the structural basis of IP3R activation and the contributions of IP3-evoked Ca2 + signals to cellular physiology. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling. 相似文献15.
16.
Bicheng Yang Xiaolu Duan Wenzheng Wu Weidong JiWenqi Wu Wen ZhongZhijian Zhao Shujue LiYang Liu Guohua Zeng 《Life sciences》2014
Aim
Promoter-targeted small activating RNAs (saRNAs) have been shown to be able to induce target gene expression, a mechanism known as RNA activation (RNAa). The present study tested whether saRNA can induce the overexpression of TRPV5 in human cells derived from the kidney and subsequently manipulate cell calcium uptake.Main methods
Three saRNAs complementary to the TRPV5 promoter were synthesized and transfected into cells. TRPV5 expression at the RNA and protein levels was analyzed by quantitative real-time PCR and Western blotting respectively. For functional study, transcellular Ca2 + transportation was tested by fura-2 analysis. Dihydrotestosterone (DHT), a suppressor of cellular calcium transportation, was administered to challenge the activating effect of selected saRNA.Key findings
One of these synthesized saRNAs, ds-2939, significantly induced the expression of TRPV5 at both mRNA and protein levels. Fura-2 analysis revealed that the intracellular Ca2 + concentration was elevated by ds-2939. DHT treatment reduced transmembrane Ca2 + transport, which was partially antagonized by ds-2939.Significance
Our results suggest that a saRNA targeting TRPV5 promoter can be utilized to manipulate the transmembrane Ca2 + transport by upregulating the expression of TRPV5 and may serve as an alternative for the treatment of Ca2 + balance-related diseases. 相似文献17.
18.
Andrew W. Farrell Safina GadeockAleta Pupovac Bin WangIman Jalilian Marie RansonRonald Sluyter 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
The extracellular ATP-gated cation channel, P2X7 receptor, has an emerging role in neoplasia, however progress in the field is limited by a lack of malignant cell lines expressing this receptor.Methods
Immunofluorescence labelling and a fixed-time ATP-induced ethidium+ uptake assay were used to screen a panel of human malignant cell lines for the presence of functional P2X7. The presence of P2X7 was confirmed by RT-PCR, immunoblotting and pharmacological approaches. ATP-induced cell death was measured by colourimetric tetrazolium-based and cytofluorometric assays. ATP-induced CD23 shedding was measured by immunofluorescence labelling and ELISA.Results
RPMI 8226 multiple myeloma cells expressed P2X7 mRNA and protein, as well as P2X1, P2X4 and P2X5 mRNA. ATP induced ethidium+ uptake into these cells with an EC50 of ~ 116 μM, and this uptake was reduced in the presence of extracellular Ca2+ and Mg2+. The P2X7 agonist 2'- and 3'-0(4-benzoylbenzoyl) ATP, but not UTP, induced ethidium+ uptake. ATP-induced ethidium+ uptake was impaired by the P2X7 antagonists, KN-62 and A-438079. ATP induced death and CD23 shedding in RPMI 8226 cells, and both processes were impaired by P2X7 antagonists. The metalloprotease antagonists, BB-94 and GM6001, impaired ATP-induced CD23 shedding but not ethidium+ uptake.Conclusions
P2X7 receptor activation induces cell death and CD23 shedding in RPMI 8226 cells.General significance
RPMI 8226 cells may be useful to study the role of P2X7 in multiple myeloma and B-lymphocytes. 相似文献19.
Peter Schönfeld Nicol Kruska Georg Reiser 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009,1790(12):1698-1704
Background
Hydroxy-1-aryl-isochromans (HAIC) are newly emerging natural polyphenolic antioxidants, enriched in extravirgin olive oil, whose antioxidative potency was only scarcely characterized using cell-free systems and cells.Methods
We characterized the activity of HAIC to inactivate reactive oxygen species (ROS) generated by the xanthine/xanthine oxidase system, mitochondria (rat brain) and neural cells. ROS levels were estimated using ROS-sensitive probes, such as Amplex Red, MitoSOXRED.Results
HAIC (with 2, 3 or 4 hydroxyl substituents) effectively scavenge ROS released from mitochondria. EC50 values estimated with mitochondria and submitochondrial particles were around 20 μM. Moreover, in PC12 and cultured neural primary cells, HAIC buffered cytosolic ROS. Although HAIC permeate biological membranes, HAIC fail to buffer matrix ROS in isolated mitochondria. We show that hydrogen peroxide was effectively abolished by HAIC, whereas the production of superoxide was not affected.Conclusion
HAIC exert high antioxidative activity to reduce hydrogen peroxide. The antioxidative activity of HAIC is comparable with that of the stilbene-like, polyphenolic resveratrol, but much higher than that of trolox, N-acetylcysteine or melatonin.General significance
Unlike resveratrol, HAIC do not impair mitochondrial ATP synthesis or Ca2+ retention by mitochondria. Thus, HAIC have the decisive advantage to be potent antioxidants with no detrimental side effects on mitochondrial functions. 相似文献20.
Kevin Thurley Alexander Skupin Rüdiger Thul Martin Falcke 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012