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51.
Signalling by protein kinase C isoforms in the heart 总被引:11,自引:0,他引:11
Understanding transmembrane signalling process is one of the major challenge of the decade. In most tissues, since Fisher and Krebs's discovery in the 1950's, protein phosphorylation has been widely recognized as a key event of this cellular function. Indeed, binding of hormones or neurotransmitters to specific membrane receptors leads to the generation of cytosoluble second messengers which in turn activate a specific protein kinase. Numerous protein kinases have been so far identified and roughly classified into two groups, namely serine/threonine and tyrosine kinases on the basis of the target amino acid although some more recently discovered kinases like MEK (or MAP kinase kinase) phosphorylate both serine and tyrosine residues.Protein kinase C is a serine/threonine kinase that was first described by Takai et al. [1] as a Ca- and phospholipid-dependent protein kinase. Later on, Kuo et al. [2] found that PKC was expressed in most tissues including the heart. The field of investigation became more complicated when it was found that the kinase is not a single molecular entity and that several isoforms exist. At present, 12 PKC isoforms and other PKC-related kinases [3] were identified in mammalian tissues. These are classified into three groups. (1) the Ca-activated -, -,and -PKCs which display a Ca-binding site (C2); (2) the Ca-insensitive -, -, -, -, and -PKCs. The kinases that belong to both of these groups display two cystein-rich domains (C1) which bind phorbol esters (for recent review on PKC structure, see [4]). (3) The third group was named atypical PKCs and include , , and -PKCs that lack both the C2 and one cystein-rich domain. Consequently, these isoforms are Ca-insensitive and cannot be activated by phorbol esters [5]. In the heart. evidence that multiple PKC isoforms exist was first provided by Kosaka et al. [6] who identified by chromatography at least two PKC-related isoenzymes. Numerous studies were thus devoted to the biochemical characterization of these isoenzymes (see [7] for review on cardiac PKCs) as well as to the identification of their substrates.This overview aims at updating the present knowledge on the expression, activation and functions of PKC isoforms in cardiac cells. (Mol Cell Biochem 157: 65–72, 1996) 相似文献
52.
INTRODUCTI0NThedifferentiati0nofcelIsalongthemonocyte-macr0phagepathwayandthesig-nalsinvo1vedinthesecel1sacquiringtheabilitytokilltum0rcellsarenotfllllyundersto0d.Wehavebeenstudingamoleculewhichappearst0beanimportantmemberofthecytokinenetworkinvo1vedintheregulati0nmonocyteactivation.ThiscytokinetermedP48wasisolatedfr0mthehllmannullcellleukemiacell1ineReh.IthasbeenpurifiedtohomogeneityandfOundtobedistinctfrominterferongamma,col0nystimulatingfactors(CSFs)andTNFalphaalldbeta[1,2].Func-ti… 相似文献
53.
54.
Since cytoplasmic Ca2+ levels are reported to regulate neurite elongation, we tested whether calcium-activated kinases might be necessary for growth cone motility and neurite elongation in explant cultures of goldfish retina. Kinase inhibitors and activators were locally applied by micropipette to retinal growth cones and the responses were observed via phase-contrast videomicroscopy. In some cases, growth rates were also quantifed over several hours after general application in the medium. The selective inhibitors of protein kinase C, calphostin C (0.1–1 μM) and chelerythrin (up to 50 μM), caused no obvious changes in growth cones or neurite elongation, and activators of PKC (phorbols, arachidonic acid, and diacylglycerol) also were generally without effects, although phorbols slowed the growth rate. Inhibitors of protein kinase A and tyrosine kinases also produced no obvious effects. The calmodulin antagonists, calmidazolium (0.1 μM), trifluoperazine (100 μM), and CGS9343B (50 μM), however, caused a reversible growth cone arrest with loss of filopodia and lamellipodia. The growth cone became a club-shaped swelling which sometimes moved a short distance back the shaft, leaving evacuated filaments at points of strong filopodial attachments. A similar reversible growth cone arrest occurred with the general kinase inhibitors: H7 at 200 but not at 100 μM, and staurosporine at 100 but not 10 nM, suggesting possible involvement of a calmodulin-dependent kinase (camK) rather than PKC. The selective inhibitor of camKII, KN-62 (tested up to 50 μM), produced no effects but the specific myosin light-chain kinase (MLCK) inhibitors ML-7 (3–5 μM) and ML-9 (5–10 μM) reversibly reproduced the effect, suggesting that MLCK rather than camKII is necessary for growth cone motility. The MLCK inhibitors' effects both on growth cone morphology and on F-actin filaments (rhodamine-phalloidin staining) were similar to those caused by cytochalasin D (5 μM), and are discussed in light of findings that inhibiting MLCK disrupts actin filaments in astrocytes and fibroblasts. 1994 John Wiley & Sons, Inc. 相似文献
55.
Mortimer M. Civan Jonathan Robbins Simon Broad Enrique Rozengurt David A. Brown 《The Journal of membrane biology》1993,133(1):51-59
Summary Differentiated neuroblastoma cells exhibit both the delayed rectifier potassium current (I
K) and the M-current (I
M). The present study was designed to determine the roles of protein kinase C (PKC) and of the calmodulin-binding protein 80K/MARCKS, a prominent substrate for PKC and possible regulator of these currents. Neuroblastoma x glioma (NG108-15) hybrid cells transfected with m1 muscarinic receptors were grown with 1% fetal bovine serum (FBS) without the prostaglandin E1 (PGE1) and isobutylmethylxanthine (IBMX) usually added in preparation for electrophysiological studies. Under these conditions, the usual pleomorphism was largely abolished, leaving two populations of small cells with stellate and spherically symmetrical geometries. Whole-cell patch clamping indicated that the two cell types had identical electrophysiological properties, displaying: I
k, a small current through a T-like Ca2+ channel, and no M-current.Stimulation with carbachol shifted the distribution of cells to a more stellate morphology within 24 hr and later (after 48 hr) reduced the PKC substrate 80K/MARCKS by 22±7%. In contrast to the stimulation of I
k observed with cardiac cells, PKC activation produced only a small inhibition of I
k, which was independent of carbachol pretreatment. Thus, PKC and 80K/MARCKS can be dissociated from the regulation of I
k in neuroblastoma cells.Supported in part by research grants from the National Institutes of Health (DK-40145 and EY-08343) and from the U.K. Medical Research Council.We thank Dr. Peter J. Parker for his generous gift of PKC, and Yvonne Vallis for her skillful assistance with the cultures and harvesting of the NG108-15 transfected cells. 相似文献
56.
本文报道在我国广西隆林壮族中发现一个罕見的HbQ复合α,β地中海贫血家系。先证者女,18岁,贫血面容,肝脾肿大。化学结构分析确证本Hb变异体为HbQ Thailand[α74(EF3)Asp→His]。血红蛋白组成以及α和β珠蛋白基因分析结果表明,先证者的珠蛋白基因型为-α~Q/-α~T复合β°/β°(IVSI-1G→T/Codon17A→T);先证者父的基因型为-‘α~Q/-复合β~O/β~A(IVSI-1G→T/β~A);先证母的基因型为-α~T/αα复合β~O/β~A(Codon17A→T/β~A)。 相似文献
57.
本文就HHT、RA、WB_(852)对HL-60细胞的诱导分化作用及此过程中PKC活力在细胞胞浆部分及膜溶脱部分的变化进行研究。结果表明,在适当的用药浓度下,从细胞生长抑制情况、形态学观察及NBT还原能力测定判断,三种药物对HL-60细胞有明显的诱导分化作用。PKC活力分布变化的研究结果表明,用药组细胞胞浆部分酶活力有不同程度的下降,尤在用药早期(约6h以前)下降显著;而膜部分PKC活力则表现上升、或下降,或活力相差不大的结果。暗示在信息传递过程中起核心作用的PKC对不同的胞外刺激可能采取不同的应答方式。PKC的作用可能主要发生在信息传递的早期。 相似文献
58.
Jörg Müller Oliver Mitesser Marc W. Cadotte Fons van der Plas Akira S. Mori Christian Ammer Anne Chao Michael Scherer-Lorenzen Petr Baldrian Claus Bässler Peter Biedermann Simone Cesarz Alice Claßen Benjamin M. Delory Heike Feldhaar Andreas Fichtner Torsten Hothorn Claudia Kuenzer Marcell K. Peters Kerstin Pierick Thomas Schmitt Bernhard Schuldt Dominik Seidel Diana Six Ingolf Steffan-Dewenter Simon Thorn Goddert von Oheimb Martin Wegmann Wolfgang W. Weisser Nico Eisenhauer 《Global Change Biology》2023,29(6):1437-1450
Intensification of land use by humans has led to a homogenization of landscapes and decreasing resilience of ecosystems globally due to a loss of biodiversity, including the majority of forests. Biodiversity–ecosystem functioning (BEF) research has provided compelling evidence for a positive effect of biodiversity on ecosystem functions and services at the local (α-diversity) scale, but we largely lack empirical evidence on how the loss of between-patch β-diversity affects biodiversity and multifunctionality at the landscape scale (γ-diversity). Here, we present a novel concept and experimental framework for elucidating BEF patterns at α-, β-, and γ-scales in real landscapes at a forest management-relevant scale. We examine this framework using 22 temperate broadleaf production forests, dominated by Fagus sylvatica. In 11 of these forests, we manipulated the structure between forest patches by increasing variation in canopy cover and deadwood. We hypothesized that an increase in landscape heterogeneity would enhance the β-diversity of different trophic levels, as well as the β-functionality of various ecosystem functions. We will develop a new statistical framework for BEF studies extending across scales and incorporating biodiversity measures from taxonomic to functional to phylogenetic diversity using Hill numbers. We will further expand the Hill number concept to multifunctionality allowing the decomposition of γ-multifunctionality into α- and β-components. Combining this analytic framework with our experimental data will allow us to test how an increase in between patch heterogeneity affects biodiversity and multifunctionality across spatial scales and trophic levels to help inform and improve forest resilience under climate change. Such an integrative concept for biodiversity and functionality, including spatial scales and multiple aspects of diversity and multifunctionality as well as physical and environmental structure in forests, will go far beyond the current widely applied approach in forestry to increase resilience of future forests through the manipulation of tree species composition. 相似文献
59.
Opale Coutant Céline Jézéquel Karel Mokany Isabel Cantera Raphaël Covain Alice Valentini Tony Dejean Sébastien Brosse Jérôme Murienne 《Global Change Biology》2023,29(7):1741-1758
Freshwater ecosystems are among the most endangered ecosystem in the world. Understanding how human activities affect these ecosystems requires disentangling and quantifying the contribution of the factors driving community assembly. While it has been largely studied in temperate freshwaters, tropical ecosystems remain challenging to study due to the high species richness and the lack of knowledge on species distribution. Here, the use of eDNA-based fish inventories combined to a community-level modelling approach allowed depicting of assembly rules and quantifying the relative contribution of geographic, environmental and anthropic factors to fish assembly. We then used the model predictions to map spatial biodiversity and assess the representativity of sites surveyed in French Guiana within the EU Water Framework Directive (WFD) and highlighted areas that should host unique freshwater fish assemblages. We demonstrated a mismatch between the taxonomic and functional diversity. Taxonomic assemblages between but also within basins were mainly the results of dispersal limitation resulting from basin isolation and natural river barriers. Contrastingly, functional assemblages were ruled by environmental and anthropic factors. The regional mapping of fish diversity indicated that the sites surveyed within the EU WFD had a better representativity of the regional functional diversity than taxonomic diversity. Importantly, we also showed that the assemblages expected to be the most altered by anthropic factors were the most poorly represented in terms of functional diversity in the surveyed sites. The predictions of unique functional and taxonomic assemblages could, therefore, guide the establishment of new survey sites to increase fish diversity representativity and improve this monitoring program. 相似文献
60.
The protective effect of arbutin against potassium bromate-induced oxidative damage in the rat brain
H. Turan Akkoyun Ahmet Uyar Mahire Bayramoglu Akkoyun Aydın Şükrü Bengü Şule Melek Fatma Karagözoğlu Sevinç Aydın Suat Ekin Sinem Aslan Erdem 《Journal of biochemical and molecular toxicology》2023,37(2):e23248
This study aimed to investigate the protective effects of arbutin (ARB) against brain injury induced in rats with potassium bromate (KBrO3). The rats were divided into four groups as Group 1: Control (0.9% NaCl ml/kg/day p.), Group 2: KBrO3 (100 mg/kg (gavage), Group 3: ARB (50 mg/kg/day p.), and Group 4: KBrO3 + ARB (100 mg/kg (gavage) + 50 mg/kg/day p.). At the end of the fifth day of the study, the rats in all groups were killed, and their brain tissues were collected. In the collected brain tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured, and routine histopathological examinations were made. The MDA levels in the group that was exposed to KBrO3 were significantly higher than those in the control group (p ˂ 0.001). In comparison to the KBrO3 group, the MDA levels in the KBrO3 + ARB group were significantly lower (p ˂ 0.001). It was observed that SOD and CAT enzyme activity levels were significantly lower in the KBrO3 group compared to the control group (p ˂ 0.001), while these levels were significantly higher in the KBrO3 + ARB group than in the KBrO3 group (p ˂ 0.001). Additionally, the group that was subjected to KBrO3 toxicity, as well as ARB administration, had much lower levels of histopathologic signs than the group that was subjected to KBrO3 toxicity only. Consequently, it was found that KBrO3 exposure led to injury in the brain tissues of the rats, and using ARB was effective in preventing this injury. 相似文献