Abstract:
:Cytotoxic brain edema triggered by neuronal swelling is the chief cause of mortality following brain trauma and cerebral infarct. Using fluorescence lifetime imaging to analyze contributions of intracellular ionic changes in brain slices, we find that intense Na(+) entry triggers a secondary increase in intracellular Cl(-) that is required for neuronal swelling and death. Pharmacological and siRNA-mediated knockdown screening identified the ion exchanger SLC26A11 unexpectedly acting as a voltage-gated Cl(-) channel that is activated upon neuronal depolarization to membrane potentials lower than -20 mV. Blockade of SLC26A11 activity attenuates both neuronal swelling and cell death. Therefore cytotoxic neuronal edema occurs when sufficient Na(+) influx and depolarization is followed by Cl(-) entry via SLC26A11. The resultant NaCl accumulation causes subsequent neuronal swelling leading to neuronal death. These findings shed light on unique elements of volume control in excitable cells and lay the ground for the development of specific treatments for brain edema.
journal_name
Celljournal_title
Cellauthors
Rungta RL,Choi HB,Tyson JR,Malik A,Dissing-Olesen L,Lin PJC,Cain SM,Cullis PR,Snutch TP,MacVicar BAdoi
10.1016/j.cell.2015.03.029subject
Has Abstractpub_date
2015-04-23 00:00:00pages
610-621issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00316-5journal_volume
161pub_type
杂志文章相关文献
CELL文献大全abstract::Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(89)90756-3
更新日期:1989-12-22 00:00:00
abstract::Receptor-mediated endocytosis of specific ligands is mediated through clustering of receptor-ligand complexes in coated pits on the cell surface. Following this clustering event, the ligand is internalized into a noncoated intracellular vesicle, the receptosome, which selectively avoids fusion with lysosomes and moves...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90115-4
更新日期:1980-08-01 00:00:00
abstract::At anaphase onset, the protease separase triggers chromosome segregation by cleaving the chromosomal cohesin complex. Here, we show that cohesin destruction in metaphase is sufficient for segregation of much of the budding yeast genome, but not of the long arm of chromosome XII that contains the rDNA repeats. rDNA in ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(04)00415-5
更新日期:2004-05-14 00:00:00
abstract::Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS, a cascade of transcription factors, the "temporal gene cascade," has been identified that acts to alter progenitor competence over time. However, ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.10.032
更新日期:2009-11-25 00:00:00
abstract::Chemical modifications of histones and DNA, such as histone methylation, histone acetylation, and DNA methylation, play critical roles in epigenetic gene regulation. Many of the enzymes that add or remove such chemical modifications are known, or might be suspected, to be sensitive to changes in intracellular metaboli...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2013.03.004
更新日期:2013-03-28 00:00:00
abstract::The JAK/STAT signaling pathway, renowned for its effects on cell proliferation and survival, is constitutively active in various human cancers, including ovarian. We have found that JAK and STAT are required to convert the border cells in the Drosophila ovary from stationary, epithelial cells to migratory, invasive ce...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(01)00607-9
更新日期:2001-12-28 00:00:00
abstract::Previous work on Drosophila santomea suggested that its absence of abdominal pigmentation, compared to the other darkly pigmented species, is based on mutations in the cis-regulatory region of tan, inactivating the expression of that gene in the abdomen of D. santomea males and females. Our discovery that D. santomea ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.10.033
更新日期:2009-12-11 00:00:00
abstract::Competence development and sporulation in B. subtilis are partly controlled by peptides that accumulate in culture medium as cells grow to high density. We constructed two genes that encode mature forms of two different signaling molecules, the PhrA peptide that stimulates sporulation, and CSF, the competence- and spo...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80277-9
更新日期:1997-06-13 00:00:00
abstract::The bHLH-ZIP protein Mad heterodimerizes with Max as a sequence-specific transcriptional repressor. Mad is rapidly induced upon differentiation, and the associated switch from Myc-Max to Mad-Max heterocomplexes seem to repress genes normally activated by Myc-Max. We have identified two related mammalian cDNAs that enc...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90355-0
更新日期:1995-03-10 00:00:00
abstract::We investigated soybean lectin gene structure and expression in a genetic line that accumulates normal levels of seed lectin (Le+ line) and in a mutant line that produces no detectable seed lectin (Le- line). We found that the nuclear and cytoplasmic lectin RNA levels in Le- embryos are approximately 0.01% of those in...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(83)90428-2
更新日期:1983-06-01 00:00:00
abstract::The 2.2 kb mRNA of the Dictyostelium discoideum prespore gene EB4-PSV is constitutively transcribed during growth and development, but the message is only accumulated when cells form aggregates and establish the prespore-prestalk pattern. Disruption of the pattern by mechanical disaggregation results in a rapid loss o...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90130-5
更新日期:1992-04-03 00:00:00
abstract::We wished to learn whether the genomes of strains of EMB isolated from patients with infectious mononucleosis are consistently distinguishable from those of strains from Burkitt's lymphoma. The genome of a new transforming strains (FF41) of EBV isolated from saliva of a patient with uncomplicated infectious mononucleo...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90345-7
更新日期:1981-05-01 00:00:00
abstract::We have identified in mice an allele of a new T cell receptor V beta gene, V beta 17a, whose product is bound by the monoclonal antibody KJ23a. Over 90% of T cell hybridomas prepared from V beta 17a+ T cells of SWR mice respond to allogeneic forms of the IE class II MHC protein, indicating that V beta 17a has an appre...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90567-8
更新日期:1987-04-24 00:00:00
abstract::Several metabolic alterations accumulate over time along with a reduction in biological fitness, suggesting the existence of a "metabolic clock" that controls aging. Multiple inborn defects in metabolic circuitries accelerate aging, whereas genetic loci linked to exceptional longevity influence metabolism. Each of the...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2016.07.031
更新日期:2016-08-11 00:00:00
abstract::Cellular ras activity has been neutralized in 3T3 cells by microinjection of a specific anti-ras monoclonal antibody. The injected antibody efficiently inhibited proliferation in cells treated with a phorbol ester and a calcium ionophore, or with prostaglandin F2 alpha. These treatments were designed to imitate the ac...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90531-4
更新日期:1988-01-15 00:00:00
abstract::K-Ras is targeted to the plasma membrane by a C-terminal membrane anchor that comprises a farnesyl-cysteine-methyl-ester and a polybasic domain. We used quantitative spatial imaging and atomistic molecular dynamics simulations to examine molecular details of K-Ras plasma membrane binding. We found that the K-Ras ancho...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2016.11.059
更新日期:2017-01-12 00:00:00
abstract::Yeast mutants lacking meiotic proteins Zip1, Zip2, Zip3, Mer3, and/or Msh5 (ZMMs) were analyzed for recombination, synaptonemal complex (SC), and meiotic progression. At 33 degrees C, recombination-initiating double-strand breaks (DSBs) and noncrossover products (NCRs) form normally while formation of single-end invas...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(04)00292-2
更新日期:2004-04-02 00:00:00
abstract::Signaling proteins from the same family can have markedly different roles in a given cellular context. Here, we show that expression of one hundred constitutively active human small GTPases induced cell morphologies that fell into nine distinct classes. We developed an algorithm for pairs of classes that predicted ami...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00315-5
更新日期:2003-05-02 00:00:00
abstract::The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.09.028
更新日期:2017-11-02 00:00:00
abstract::Secretory proteins are segregated from cytosolic proteins by their translocation into the endoplasmic reticulum (ER). A modified secretory protein trapped during translocation across the ER membrane can be crosslinked to two previously identified proteins, Sec61p and BiP (Kar2p). The dependence of this cross-linking u...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90415-9
更新日期:1992-04-17 00:00:00
abstract::Following EMS mutagenesis we recovered a mutant of D. melanogaster that grows at concentrations of alpha-amanitin lethal to wild-type. To our knowledge this mutant represents the first example of an amanitin-resistant eucaryotic organism. The amanitin resistance of the mutant (AmaC4) is due to an alteration in its DNA...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90116-8
更新日期:1979-11-01 00:00:00
abstract::Telomeres of Oxytricha nova macronuclear chromosomes consist of a repeated T4G4 sequence, single-stranded at the 3' terminus, bound by a heterodimeric protein. The cloning of genes for the two polypeptides and their separate expression in E. coli have enabled evaluation of their individual contributions to DNA binding...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(91)90075-a
更新日期:1991-11-15 00:00:00
abstract::A gene for Saccharomyces cerevisiae tRNATrp has been sequenced which contains an intervening sequence of 34 bp (H. S. Kang and J. Abelson, unpublished results). The mutant yeast strain ts-136 accumulates a precursor to tRNATrp which contains mature ends and is colinear with the tRNATrp gene. A nuclear extract from Xen...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90166-1
更新日期:1979-06-01 00:00:00
abstract::Pulsed field gradient gel electrophoresis fractionates chromosome-sized DNA molecules from T. brucei. About 60% of the DNA remains in or close to the gel slot (large DNA). There are about three chromosomes of approximately 2 Mb, at least six chromosomes of 200-700 kb, and roughly a hundred mini-chromosomes of 50-150 k...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(84)90302-7
更新日期:1984-05-01 00:00:00
abstract::The global financial crisis has hit biotech companies hard both in the US and Europe as venture capital dries up. Finding new sources of long-term financing for translating research into new therapeutics will be essential for maintaining innovation and new drug development by biotech companies. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.07.026
更新日期:2009-08-07 00:00:00
abstract::NAD(+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2013.06.016
更新日期:2013-07-18 00:00:00
abstract::Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tiss...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.12.021
更新日期:2015-01-15 00:00:00
abstract::In this issue, Baumann et al. (2007) identify a helicase PICH that localizes to "threads" that remain connected between sister kinetochores after they have separated in anaphase. These threads are thought to be catenated centromeric DNA. PICH contributes to the mitotic checkpoint by recruiting Mad2 to kinetochores and...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2006.12.022
更新日期:2007-01-12 00:00:00
abstract::Conditions are described for programming with active transcription complexes essentially all the Xenopus 5S RNA genes added to an extract of Xenopus oocyte nuclei. We call this rate enhancement. Transcription by SP6 RNA polymerase of either strand of a Xenopus 5S RNA gene is unimpeded by the presence of a complete tra...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(86)90459-9
更新日期:1986-02-14 00:00:00
abstract::Humans are uniquely susceptible to typhoid fever caused by infection with Salmonella enterica serovar Typhi. Mathur et al. now report that mice lacking Toll-like receptor 11, which is absent in humans, can be lethally infected with S. Typhi, a breakthrough that promises to speed the development of better vaccines. ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2012.10.016
更新日期:2012-10-26 00:00:00