Abstract:
:We have previously shown that in neutrophils deprived of granulocyte colony-stimulating factor, apoptosis is preceded by acidification and that the protection against apoptosis conferred on neutrophils by granulocyte colony-stimulating factor is dependent upon delay of this acidification. To test the hypothesis that acidification could be a general feature of apoptosis, we examined intracellular pH changes in another cell line. Jurkat cells, a T-lymphoblastoid line, were induced to undergo apoptosis with anti-Fas IgM, cycloheximide, or exposure to short-wavelength UV light. We found that acidification occurred in response to treatment with these agents and that acidification preceded DNA fragmentation. Jurkat cells were also found to possess an acid endonuclease that is active below pH 6.8, compatible with a possible role for this enzyme in chromatin digestion during apoptosis. Incubation of the cells with the bases imidazole or chloroquine during treatment with anti-Fas antibody or cycloheximide or after UV exposure decreased apoptosis as assessed by nuclear morphology and DNA content. The alkalinizing effect of imidazole and chloroquine was shown by the demonstration that the percentage of cells with an intracellular pH below 6.8 after treatment with anti-Fas antibody, cycloheximide, or UV was diminished in the presence of base as compared with similarly treated cells incubated in the absence of base. We conclude that acidification is an early event in programmed cell death and may be essential for genome destruction.
journal_name
Proc Natl Acad Sci U S Aauthors
Gottlieb RA,Nordberg J,Skowronski E,Babior BMdoi
10.1073/pnas.93.2.654subject
Has Abstractpub_date
1996-01-23 00:00:00pages
654-8issue
2eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::F1-ATPase, the catalytic domain of ATP synthase, synthesizes most of the ATP in living organisms. Running in reverse powered by ATP hydrolysis, this hexameric ring-shaped molecular motor formed by three αβ-dimers creates torque on its central γ-subunit. This reverse operation enables detailed explorations of the mecha...
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.1305497110
更新日期:2013-10-08 00:00:00
abstract::Germ-line mutations of tumor suppressor genes confer strong predisposition to tumor formation. In the rat, a form of dominantly inherited renal carcinoma (RC) results in multiple chromophobe cell tumors that resemble the human disease, and heterozygous carriers (RC/+) are highly susceptible to environmental agents (ra...
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.90.17.8038
更新日期:1993-09-01 00:00:00
abstract::Ribavirin is a nucleotide analog that can be incorporated by viral polymerases, causing mutations by allowing base mismatches. It is currently used therapeutically as an antiviral drug during hepatitis C virus infections. During the amplification of poliovirus genomic RNA or hepatitis C replicons, error frequency is k...
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.1232294100
更新日期:2003-06-10 00:00:00
abstract::Serial passage of simian virus 40 (SV40) at high multiplicity of infection leads to the emergence of variants with deleted, substituted, and/or duplicated DNA. Individual variants have been cloned by selective complementation with temperature sensitive SV40 mutants, or nonselectively by coinfection of cells with wild-...
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.71.3.942
更新日期:1974-03-01 00:00:00
abstract::The effective management of marine fisheries is an ongoing challenge at the intersection of biology, economics, and policy. One way in which fish stocks-and their habitats-can be protected is through the establishment of marine reserves, areas that are closed to fishing. Although the potential economic benefits of suc...
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.1518509113
更新日期:2016-04-05 00:00:00
abstract::Brain areas' functional repertoires are shaped by their incoming and outgoing structural connections. In empirically measured networks, most connections are short, reflecting spatial and energetic constraints. Nonetheless, a small number of connections span long distances, consistent with the notion that the functiona...
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.1720186115
更新日期:2018-05-22 00:00:00
abstract::Although adaptor ADAP (FYB) and its binding to SLP-76 has been implicated in TcR-induced "inside-out" signaling for LFA-1 activation in T cells, little is known regarding its role in LFA-1-mediated "outside-in" signaling. In this study, we demonstrate that ADAP and SLP-76-ADAP binding are coupled to LFA-1 costimulatio...
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.0900510106
更新日期:2009-07-28 00:00:00
abstract::Cellular senescence is defined by the limited proliferative capacity of normal cultured cells. Immortal cells overcome this regulation and proliferate indefinitively. One step in the immortalization process may be reactivation of telomerase activity, a ribonucleoprotein complex, which, by de novo synthesized telomeric...
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.93.13.6476
更新日期:1996-06-25 00:00:00
abstract::Different experimental structures of the same protein or of proteins with high sequence similarity contain many small variations. Here we construct ensembles of "high-sequence similarity Protein Data Bank" (HSP) structures and consider the extent to which such ensembles represent the structural heterogeneity of the na...
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.0511156103
更新日期:2006-07-18 00:00:00
abstract::Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, or to the chemotherapeutically inactive trans isomer trans-DDP were elicited by immunization with calf thymus DNA modified with either cis- or trans-DDP at ratios of bound platin...
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.84.23.8225
更新日期:1987-12-01 00:00:00
abstract::We identified cell surface markers associated with repression of p16(INK4a)/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plast...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1218682110
更新日期:2013-03-19 00:00:00
abstract::Replication-defective human adenovirus (Ad) group C transducing vectors, most of which have the E1A, E1B, and E3 genes deleted, are highly inflammatory despite the fact that the parental viruses typically cause subclinical or mild infections. To investigate this paradox, the roles that the E1A, E1B, and E3 genes play ...
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.0303709101
更新日期:2004-03-02 00:00:00
abstract::Key predictions of the Hubble law are inconsistent with direct observations on equitable complete samples of extragalactic sources in the optical, infrared, and x-ray wave bands-e.g., the predicted dispersion in apparent magnitude is persistently greatly in excess of its observed value, precluding an explanation via h...
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.90.11.4798
更新日期:1993-06-01 00:00:00
abstract::Examples from various plant and animal groups indicate that there has been a general increase in potential versatility of form, determined by the number and range of independently varying morphogenetic parameters, among taxa appearing at successively younger stages in the fossil record. Taxa or body plans with higher ...
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.70.7.1936
更新日期:1973-07-01 00:00:00
abstract::Soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) protein interactions at the synaptic vesicle/plasma membrane interface play an essential role in neurotransmitter release. The membrane-proximal region (amino acids 77-90) of the v-SNARE vesicle-associated membrane protein 2 (VAMP 2,...
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.0303274101
更新日期:2004-02-10 00:00:00
abstract::C1q-like genes (C1ql1-C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but who...
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.1019577108
更新日期:2011-02-08 00:00:00
abstract::Plants produce a wide range of allelochemicals to defend against herbivore attack, and generalist herbivores have evolved mechanisms to avoid, sequester, or detoxify a broad spectrum of natural defense compounds. Successful arthropod pests have also developed resistance to diverse classes of pesticides and this adapta...
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.1213214110
更新日期:2013-01-08 00:00:00
abstract::For a number of viruses, oligomerization is a critical component of envelope processing and surface expression. Previously, we reported that a synthetic peptide (DP-107) corresponding to the putative leucine zipper region (aa 553-590) of the transmembrane protein (gp41) of human immunodeficiency virus type 1 (HIV-1) e...
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.91.26.12676
更新日期:1994-12-20 00:00:00
abstract::Adult stem cells represent unique populations of undifferentiated cells with self-renewal capacity. In many tissues, stem cells divide less often than their progeny. It has been widely speculated, but largely untested, that their undifferentiated and quiescent state may make stem cells more efficient as donors for clo...
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.0611358104
更新日期:2007-02-20 00:00:00
abstract::The in vitro biological activities of several rabies virus-neutralizing monoclonal antibodies (mAbs) were compared with their ability to prevent a lethal rabies virus encephalomyelitis. The protective activity of a particular mAb in vivo did not correlate with its virus-neutralizing activity in vitro; rather it was 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.89.15.7252
更新日期:1992-08-01 00:00:00
abstract::Extracellular vesicles (EVs) secreted by cells present an attractive strategy for developing new therapies, but progress in the field is limited by several issues: The quality of the EVs varies with the type and physiological status of the producer cells; protocols used to isolate the EVs are difficult to scale up; an...
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.1522297113
更新日期:2016-01-05 00:00:00
abstract::Voltage-gated Na(+) channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltage-driven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking...
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.1116449108
更新日期:2011-11-15 00:00:00
abstract::Many ion channels exhibit a slow stochastic switching between distinct modes of gating activity. This feature of channel behavior has pronounced implications for the dynamics of ionic currents and the signaling pathways that they regulate. A canonical example is the inositol 1,4,5-trisphosphate receptor (IP3R) channel...
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.1604090113
更新日期:2016-09-06 00:00:00
abstract::Brain src protooncogene is expressed in two forms, one identical to message in other tissues, and one containing an 18-nucleotide insert specific to brain. We have mapped mRNA for the two forms of src in rat brain with selective antisense oligonucleotide probes to the brain (src+) and peripheral (src-) forms. Fetal ra...
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.85.24.9831
更新日期:1988-12-01 00:00:00
abstract::The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These ob...
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.73.12.4454
更新日期:1976-12-01 00:00:00
abstract::The history of southern Africa involved interactions between indigenous hunter-gatherers and a range of populations that moved into the region. Here we use genome-wide genetic data to show that there are at least two admixture events in the history of Khoisan populations (southern African hunter-gatherers and pastoral...
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.1313787111
更新日期:2014-02-18 00:00:00
abstract::Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in...
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.1112839109
更新日期:2012-02-28 00:00:00
abstract::Infective stages of the protozoan parasite Leishmania spp. accumulate a class of beta-1,2-mannan oligosaccharides as their major carbohydrate reserve material. Here, we describe the biosynthesis of Leishmania mannan. Mannan precursors were identified by metabolic labeling of Leishmania mexicana promastigotes with [(3)...
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.0603539103
更新日期:2006-06-20 00:00:00
abstract::It is shown that a very simple semiempirical equation represents quite accurately the thermodynamic properties of aqueous sodium chloride from 373 to 823 K. The equation comprises one Margules term and a Debye-Hückel term. Just the one Margules parameter is freely adjustable because the Debye-Hückel parameter is deter...
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.80.24.7689
更新日期:1983-12-01 00:00:00
abstract::Soon after the initiation of sporulation, Bacillus subtilis divides asymmetrically to produce sister cells that have very different developmental fates. Recently, it has been proposed that the differential gene expression which begins soon after this division is due to cell-specific activation of the transcription fac...
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.91.9.3849
更新日期:1994-04-26 00:00:00