Abstract:
:The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was recently shown to negatively regulate LPS-induced acute inflammatory responses. We previously observed that the metabolic thiol antioxidant alpha-lipoic acid (LA) inhibits LPS-induced expression of cellular adhesion molecules and adherence of monocytes to human aortic endothelial cells. Here we investigated the mechanism by which LA attenuates LPS-induced monocyte activation in vitro and acute inflammatory responses in vivo. Incubation of human monocytic THP-1 cells with LA induced phosphorylation of Akt in a time- and dose-dependent manner. In cells pretreated with LA followed by LPS, Akt phosphorylation was elevated initially and further increased during incubation with LPS. This LA-dependent increase in Akt phosphorylation was accompanied by inhibition of LPS-induced NF-kappaB DNA binding activity and up-regulation of TNFalpha and monocyte chemoattractant protein 1. Lipoic acid-dependent Akt phosphorylation and inhibition of NF-kappaB activity were abolished by the PI3K inhibitors LY294002 and wortmannin. Furthermore, LA treatment of LPS-exposed C57BL/6N mice strongly enhanced phosphorylation of Akt and glycogen synthase kinase 3beta in blood cells; inhibited the LPS-induced increase in serum concentrations and/or tissue expression of adhesion molecules, monocyte chemoattractant protein 1, and TNFalpha; and attenuated NF-kappaB activation in lung, heart, and aorta. Lipoic acid also improved survival of endotoxemic mice. All of these antiinflammatory effects of LA were abolished by treatment of the animals with wortmannin. We conclude that LA inhibits LPS-induced monocyte activation and acute inflammatory responses in vitro and in vivo by activating the PI3K/Akt pathway. Lipoic acid may be useful in the prevention of sepsis and inflammatory vascular diseases.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhang WJ,Wei H,Hagen T,Frei Bdoi
10.1073/pnas.0700305104subject
Has Abstractpub_date
2007-03-06 00:00:00pages
4077-82issue
10eissn
0027-8424issn
1091-6490pii
0700305104journal_volume
104pub_type
杂志文章abstract::Infection during the neonatal period commonly induces apnea episodes, and the proinflammatory cytokine IL-1beta may serve as a critical mediator between these events. To determine the mechanism by which IL-1beta depresses respiration, we examined a prostaglandin E(2) (PGE(2))-dependent pathway in newborn mice and huma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611468104
更新日期:2007-06-05 00:00:00
abstract::Phenotypic alterations induced by the cytokinin 6-benzylaminopurine in cell suspensions of Nicotiana plumbaginifolia were studied at the level of the NH(2)-terminal sequence of the constituent proteins. Total protein extracts were separated by classical two-dimensional PAGE, and the proteins were recovered by electrob...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.14.4806
更新日期:1987-07-01 00:00:00
abstract::The diphtheria tox repressor (DtxR) of Corynebacterium diphtheriae plays a critical role in the regulation of diphtheria toxin expression and the control of other iron-sensitive genes. The crystal structures of apo-DtxR and of the metal ion-activated form of the repressor have been solved and used to identify motifs i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.21.9843
更新日期:1995-10-10 00:00:00
abstract::High-pressure methods are increasingly used to produce new dense materials with unusual properties. Increasing efforts to understand the reaction mechanisms at the microscopic level, to set up and optimize synthetic approaches, are currently directed at carbon-based solids. A fundamental, but still unsolved, question ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0802269105
更新日期:2008-06-03 00:00:00
abstract::Lambdoid phages form clear plaques and show reduced ability to establish immunity in strains of Escherichia coli that lack adenylate cyclase or catabolite activator protein. The absence of the activator protein or cyclic AMP reduces the frequency of lysogenization, but does not prevent steady-state repressor synthesis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.2.366
更新日期:1972-02-01 00:00:00
abstract::Relatively little is understood about the dynamics of global host-pathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide trans...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0906384107
更新日期:2010-03-09 00:00:00
abstract::The enterotoxigenic Escherichia coli (ETEC) are among the most common causes of diarrheal illness and death due to diarrhea among young children in low-/middle-income countries (LMICs). ETEC have also been associated with important sequelae including malnutrition and stunting, placing children at further risk of death...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2012480117
更新日期:2020-11-17 00:00:00
abstract::Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1305923110
更新日期:2013-06-25 00:00:00
abstract::Sea urchins are a major component of recent marine communities where they exert a key role as grazers and benthic predators. However, their impact on past marine organisms, such as crinoids, is hard to infer in the fossil record. Analysis of bite mark frequencies on crinoid columnals and comprehensive genus-level dive...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1201573109
更新日期:2012-05-01 00:00:00
abstract::Retroviral gene expression is inhibited in embryonal carcinoma (EC) cells. We have constructed a recombinant retroviral vector that is capable of expressing the neomycin-resistance (neo) gene in EC cells. The critical modification that permits expression of the neo gene is the insertion of a composite simian virus 40 ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.22.7137
更新日期:1984-11-01 00:00:00
abstract::Radioimmunoassay revealed increased dynorphin A(1-8)-like immunoreactivity [dynA(1-8)LI] in the aged rat brain. Among a number of brain regions examined, an age-related dynA(1-8)LI elevation was found only in the hippocampal formation and frontal cortex. Moreover, the increase in dynA(1-8)LI in the aged hippocampus wa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.8.2948
更新日期:1989-04-01 00:00:00
abstract::A densely packed granular system is an example of an out-of-equilibrium system in the jammed state. It has been a longstanding problem to determine whether this class of systems can be described by concepts arising from equilibrium statistical mechanics, such as an effective temperature and compactivity. The measureme...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0409911102
更新日期:2005-02-15 00:00:00
abstract::3-Hydroxyanthranilic acid (HAA), a compound generated during tryptophan metabolism initiated by indoleamine 2,3-dioxygenase, is known to induce T cell death, but its molecular target is not known. Here we report that HAA inhibits NF-kappaB activation upon T cell antigen receptor engagement by specifically targeting PD...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0709261104
更新日期:2007-11-20 00:00:00
abstract::We have examined the extent of tyrosine phosphorylation of talin, a component of the cytoskeleton localized in the focal adhesions and, therefore, a potential substrate of p60v-src, the transforming protein of Rous sarcoma virus. p60v-src is a tyrosine kinase that induces high levels of phosphotyrosine and the disorga...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.15.5507
更新日期:1986-08-01 00:00:00
abstract::EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1504391112
更新日期:2015-05-12 00:00:00
abstract::All proteins of this world are constructed in compliance with the same rule. Accordingly, two totally unrelated proteins, on the average, share 30 identical tripeptides, two tetrapeptides, and one pentapeptide per 500 residues. With this in mind, the 221-residue-long influenza virus hemagglutinin II (IVHA-II), as a re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.8.3065
更新日期:1991-04-15 00:00:00
abstract::Pyramidal cells in piriform cortex receive excitatory inputs from two different sources that are segregated onto adjacent segments of their apical dendrites. The present studies show that excitatory postsynaptic potentials (EPSPs) evoked by primary olfactory tract afferents that terminate on distal apical segments dis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.4.1115
更新日期:1986-02-01 00:00:00
abstract::Theoretical models suggest that social networks influence the evolution of cooperation, but to date there have been few experimental studies. Observational data suggest that a wide variety of behaviors may spread in human social networks, but subjects in such studies can choose to befriend people with similar behavior...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0913149107
更新日期:2010-03-23 00:00:00
abstract::Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium and an emerging pathogen in humans. Transitioning from a smooth (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL producer is associated with increased virulence in zebrafish, which involves the formation of massive serpentine cords, absc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1605477113
更新日期:2016-07-19 00:00:00
abstract::We have used methods that have allowed simultaneous fluorescent staining of intracellular actin together with either myosin, filamin, or tubulin in normal rat kidney fibroblasts in monolayer culture. In the main portions of the cell body, the actin, myosin, and filamin are all present in two structures: in one, the th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.9.3883
更新日期:1977-09-01 00:00:00
abstract::Electrical coupling between pyramidal cell axons, and between interneuron dendrites, have both been described in the hippocampus. What are the functional roles of the two types of coupling? Interneuron gap junctions enhance synchrony of gamma oscillations (25-70 Hz) in isolated interneuron networks and also in network...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0337529100
更新日期:2003-02-04 00:00:00
abstract::Seed germination is a complex trait of key ecological and agronomic significance. Few genetic factors regulating germination have been identified, and the means by which their concerted action controls this developmental process remains largely unknown. Using publicly available gene expression data from Arabidopsis th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1100958108
更新日期:2011-06-07 00:00:00
abstract::As a consequence of recent developments in molecular phylogenomics, all extant orders of placental mammals have been grouped into 3 lineages: Afrotheria, Xenarthra, and Boreotheria, which originated in Africa, South America, and Laurasia, respectively. Despite this advancement, the order of divergence of these 3 linea...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0809297106
更新日期:2009-03-31 00:00:00
abstract::Rat thoracic aortic smooth muscle cells (line A10, ATCC CRL 1476) display a high density of atrial natriuretic factor (ANF) receptors. ANF stimulated the accumulation of cGMP in these cells in a time- and dose-dependent fashion. These cells are known to display a high density of vasopressin receptors of the vascular V...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.22.8492
更新日期:1986-11-01 00:00:00
abstract::Through a process called "bioturbation," burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. Here, we show that microbial communities across bioturbated, but ge...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1917494117
更新日期:2020-07-07 00:00:00
abstract::Sequestration, the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules, is characteristic of Plasmodium falciparum infections. We have studied two host factors, the spleen and antibody, that influence sequest...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.16.5075
更新日期:1983-08-01 00:00:00
abstract::Using data from the Fragile Families and Child Wellbeing Study, this study examined the effects of the Great Recession on maternal harsh parenting. We found that changes in macroeconomic conditions, rather than current conditions, affected harsh parenting, that declines in macroeconomic conditions had a stronger impac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1312398110
更新日期:2013-08-20 00:00:00
abstract::Scanning confocal fluorescence microscopy and multiphoton fluorescence microscopy were used to image the uptake of the protein lysozyme into individual ion exchange chromatography particles in a packed bed in real time. Self-sharpening concentration fronts penetrating into the particles were observed at low salt conce...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0237084100
更新日期:2003-01-21 00:00:00
abstract::To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. In that regard, wearable biosensing technologies, capable of tracking drug pharmacokinetics in noninvasively retrievable biofluids (e.g., ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2009979117
更新日期:2020-08-11 00:00:00
abstract::A full-length cDNA clone encoding a purified augmenter of liver regeneration (ALR) factor prepared from the cytosol of weanling rat livers was isolated. The 1.2-kb cDNA included a 299-bp 5' untranslated region, a 375-bp coding region, and a 550-bp 3' untranslated region. It encoded a protein consisting of 125 amino ac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.17.8142
更新日期:1994-08-16 00:00:00