Oxidative damage during aging targets mitochondrial aconitase.

Abstract:

:The mechanisms that cause aging are not well understood. The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothesized that oxidation of specific proteins is critical in controlling the rate of the aging process. Utilizing an immunochemical probe for oxidatively modified proteins, we show that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target during aging of the housefly. The oxidative damage detected immunochemically was paralleled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations which decrease aconitase activity should therefore cause a decrease in life-span. This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroacetate, an inhibitor of aconitase. The identification of a specific target of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.

authors

Yan LJ,Levine RL,Sohal RS

doi

10.1073/pnas.94.21.11168

subject

Has Abstract

pub_date

1997-10-14 00:00:00

pages

11168-72

issue

21

eissn

0027-8424

issn

1091-6490

journal_volume

94

pub_type

杂志文章
  • Flexible neural mechanisms of cognitive control within human prefrontal cortex.

    abstract::A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may...

    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.0808187106

    authors: Braver TS,Paxton JL,Locke HS,Barch DM

    更新日期:2009-05-05 00:00:00

  • Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis.

    abstract::Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-2-related protein Bcl-xL fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress. Coimmunoprecipitat...

    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.94.13.6939

    authors: Kharbanda S,Pandey P,Schofield L,Israels S,Roncinske R,Yoshida K,Bharti A,Yuan ZM,Saxena S,Weichselbaum R,Nalin C,Kufe D

    更新日期:1997-06-24 00:00:00

  • Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.

    abstract::Genetic studies in mice suggest that Wnt4 signaling antagonizes expression of male hormones and effectively blocks male development in the female embryo. We recently identified an XY intersex patient carrying a chromosomal duplication of the WNT4 locus and proposed that this patient's feminization arises from an incre...

    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.1834480100

    authors: Jordan BK,Shen JH,Olaso R,Ingraham HA,Vilain E

    更新日期:2003-09-16 00:00:00

  • Oncogenic RAS pathway activation promotes resistance to anti-VEGF therapy through G-CSF-induced neutrophil recruitment.

    abstract::Granulocyte-colony stimulating factor (G-CSF) promotes mobilization of CD11b(+)Gr1(+) myeloid cells and has been implicated in resistance to anti-VEGF therapy in mouse models. High G-CSF production has been associated with a poor prognosis in cancer patients. Here we show that activation of the RAS/MEK/ERK pathway reg...

    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.1303302110

    authors: Phan VT,Wu X,Cheng JH,Sheng RX,Chung AS,Zhuang G,Tran C,Song Q,Kowanetz M,Sambrone A,Tan M,Meng YG,Jackson EL,Peale FV,Junttila MR,Ferrara N

    更新日期:2013-04-09 00:00:00

  • Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells.

    abstract::S-nitrosation is a posttranslational, oxidative addition of NO to cysteine residues of proteins that has been proposed as a cGMP-independent signaling pathway [Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Nat Rev Mol Cell Biol 6:150-166]. A paradox of S-nitrosation is that only a small set of reactive ...

    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.0704898104

    authors: Mitchell DA,Morton SU,Fernhoff NB,Marletta MA

    更新日期:2007-07-10 00:00:00

  • Transcriptional regulation in Archaea: in vivo demonstration of a repressor binding site in a methanogen.

    abstract::The status of the Archaea as one of the three primary Domains emphasizes the importance of understanding their molecular fundamentals. Basic transcription in the Archaea resembles eucaryal transcription. However, little is known about transcriptional regulation. We have taken an in vivo approach, using genetics to add...

    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.94.4.1316

    authors: Cohen-Kupiec R,Blank C,Leigh JA

    更新日期:1997-02-18 00:00:00

  • Complementation of the temperature-sensitive defect in H5ts125 adenovirus DNA replication in vitro.

    abstract::Soluble extracts of adenovirus-infected HeLa cell nuclei support DNA replication on exogenous adenovirus DNA templates. Conditions of synthesis using both wild-type and temperature-sensitive extracts have been defined. Nuclear extracts prepared from cells permissively infected with the adenovirus mutant H5ts125 expres...

    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.76.11.5534

    authors: Kaplan LM,Ariga H,Hurwitz J,Horwitz MS

    更新日期:1979-11-01 00:00:00

  • Specific cleavage analysis of mammalian mitochondrial DNA.

    abstract::Mitochondrial DNA from several mammalian species has been digested with a site-specific restriction endonuclease (HaeIII) from Haemophilus aegyptius. A quantitative analysis of the resulting specific fragments indicates that the mtDNA of any individual mammal is predominantly a single molecular clone. Gel analysis of ...

    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.72.11.4496

    authors: Potter SS,Newbold JE,Hutchison CA 3rd,Edgell MH

    更新日期:1975-11-01 00:00:00

  • Isolation of Drosophila cyclin D, a protein expressed in the morphogenetic furrow before entry into S phase.

    abstract::During Drosophila development, nuclear and cell divisions are coordinated in response to developmental signals. In yeast and mammalian cells, signals that control cell division regulate the activity of cyclin-dependent kinases (Cdks) through proteins such as cyclins that interact with the Cdks. Here we describe two Dr...

    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.93.7.3011

    authors: Finley RL Jr,Thomas BJ,Zipursky SL,Brent R

    更新日期:1996-04-02 00:00:00

  • Nerve growth factor: activation of the classical complement pathway by specific substitution for component C1-.

    abstract::The interaction of homogeneous preparations of mouse submandibular gland nerve growth factor (NGF) with the classical complement pathway was studied. NGF was found to be capable of carrying out the enzyme activities of the first component (C1-) of the classical complement pathway (i.e., the cleavage of zymogen C4 and ...

    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.79.8.2519

    authors: Boyle MD,Young M

    更新日期:1982-04-01 00:00:00

  • Human acetyl-CoA carboxylase 1 gene: presence of three promoters and heterogeneity at the 5'-untranslated mRNA region.

    abstract::Acetyl-CoA carboxylase 1 (ACC1) catalyzes the formation of malonyl-CoA, the C2 donor for de novo synthesis of long-chain fatty acids. We have identified 64 exons, including 7 alternatively spliced minor exons (1A, 1B, 1C, 3, 5A', 5A, and 5B) in human ACC1 gene ( approximately 330 kb). The gene is regulated by three pr...

    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.1332670100

    authors: Mao J,Chirala SS,Wakil SJ

    更新日期:2003-06-24 00:00:00

  • Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function.

    abstract::Nonsteroidal anti-inflammatory drugs selective for inhibition of COX-2 increase heart failure and elevate blood pressure. The COX-2 gene was floxed and crossed into merCremer mice under the alpha-myosin heavy-chain promoter. Tamoxifen induced selective deletion of COX-2 in cardiomyocytes depressed cardiac output, and ...

    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.0805806106

    authors: Wang D,Patel VV,Ricciotti E,Zhou R,Levin MD,Gao E,Yu Z,Ferrari VA,Lu MM,Xu J,Zhang H,Hui Y,Cheng Y,Petrenko N,Yu Y,FitzGerald GA

    更新日期:2009-05-05 00:00:00

  • Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor.

    abstract::Two endocytic receptors, the low density lipoprotein (LDL) receptor (LDLR) and the LDLR-related protein (LRP), are thought to act in concert in the hepatic uptake of partially metabolized dietary lipoproteins, the chylomicron remnants. We have evaluated the role of these two receptors in the hepatic metabolism of chyl...

    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.92.10.4611

    authors: Herz J,Qiu SQ,Oesterle A,DeSilva HV,Shafi S,Havel RJ

    更新日期:1995-05-09 00:00:00

  • Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit.

    abstract::During nervous system development, synapses undergo morphological change as a function of electrical activity. In Drosophila, enhanced activity results in the expansion of larval neuromuscular junctions. We have examined whether these structural changes involve the pre- or postsynaptic partner by selectively enhancing...

    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.0406164102

    authors: Mosca TJ,Carrillo RA,White BH,Keshishian H

    更新日期:2005-03-01 00:00:00

  • Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination.

    abstract::Ig class-switch recombination (CSR) is directed by the long and repetitive switch regions and requires activation-induced cytidine deaminase (AID). One of the conserved switch-region sequence motifs (AGCT) is a preferred site for AID-mediated DNA-cytosine deamination. By using somatic gene targeting and recombinase-me...

    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.1018726108

    authors: Han L,Masani S,Yu K

    更新日期:2011-07-12 00:00:00

  • Combined effects of dissociable and undissociable local anesthetics upon ATP-induced firefly bioluminescence.

    abstract::Combined effects of two drugs present simultaneously are usually expressed as summation, synergism or potentiation, and antagonism. When the sum of the effects of each drug present separately equals the combined effect of the two drugs present simultaneously, the action is called additive or summation. However, the ex...

    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.73.6.1868

    authors: Kamaya H,Ueda I,Eyring H

    更新日期:1976-06-01 00:00:00

  • A long noncoding RNA, LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression.

    abstract::Epigenetics regulation plays a critical role in determining cell identity by controlling the accessibility of lineage-specific regulatory regions. In muscle stem cells, epigenetic mechanisms of how chromatin accessibility is modulated during cell fate determination are not fully understood. Here, we identified a long ...

    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.2005868117

    authors: Dong A,Preusch CB,So WK,Lin K,Luan S,Yi R,Wong JW,Wu Z,Cheung TH

    更新日期:2020-12-22 00:00:00

  • Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX.

    abstract::The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53--a cellular process initiated by MDM2 and/or MDMX binding to the N-terminal transactivation domain of p53. MDM2 and MDMX in many tumors confer p53 inactivation and tumor survival, and are important molecul...

    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.0900947106

    authors: Pazgier M,Liu M,Zou G,Yuan W,Li C,Li C,Li J,Monbo J,Zella D,Tarasov SG,Lu W

    更新日期:2009-03-24 00:00:00

  • Singular Integrals and the Principal Series, II.

    abstract::A further study is made of the intertwining operators for the representations of the simple Lie groups of real rank one. We extend and apply this to the higher rank case, obtaining various results dealing with reducibility of principal series and existence of complementary series. ...

    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.66.1.13

    authors: Knapp AW,Stein EM

    更新日期:1970-05-01 00:00:00

  • Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development.

    abstract::The Q fever bacterium Coxiella burnetii replicates inside host cells within a large Coxiella-containing vacuole (CCV) whose biogenesis relies on the Dot/Icm-dependent secretion of bacterial effectors. Several membrane trafficking pathways contribute membranes, proteins, and lipids for CCV biogenesis. These include the...

    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.1522811113

    authors: Martinez E,Allombert J,Cantet F,Lakhani A,Yandrapalli N,Neyret A,Norville IH,Favard C,Muriaux D,Bonazzi M

    更新日期:2016-06-07 00:00:00

  • Kinetoplast DNA minicircles: regions of extensive sequence divergence.

    abstract::Previous work has shown that the kinetoplast minicircle DNA of Leishmania species exhibits species-specific sequence divergence and this observation has led to the development of a DNA probe-based diagnostic test for leishmaniasis. In the work reported here, we demonstrate that the minicircle is composed of three type...

    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.84.2.565

    authors: Rogers WO,Wirth DF

    更新日期:1987-01-01 00:00:00

  • Relationship between in vivo degradative rates and isoelectric points of proteins.

    abstract::Previous studies have shown that in mammalian cells proteins of large molecular weight are degraded more rapidly than small ones. Evidence is presented here that half-lives of proteins are also related to their isoelectric points. A double-isotope method was used to compare degradative rates of soluble proteins separa...

    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.72.10.3893

    authors: Dice JF,Goldberg AL

    更新日期:1975-10-01 00:00:00

  • Cell-type-specific signatures of microRNAs on target mRNA expression.

    abstract::Although it is known that the human genome contains hundreds of microRNA (miRNA) genes and that each miRNA can regulate a large number of mRNA targets, the overall effect of miRNAs on mRNA tissue profiles has not been systematically elucidated. Here, we show that predicted human mRNA targets of several highly tissue-s...

    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.0511045103

    authors: Sood P,Krek A,Zavolan M,Macino G,Rajewsky N

    更新日期:2006-02-21 00:00:00

  • Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.

    abstract::Increased plasminogen-activator inhibitor 1 (PAI-1) activity is a common finding in patients with coronary heart disease. Here we provide evidence for an independent, etiological role of PAI-1 in myocardial infarction. The 4G allele of a recently described common 4/5-guanine-tract (4G/5G) polymorphism in the PAI-1 pro...

    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.92.6.1851

    authors: Eriksson P,Kallin B,van 't Hooft FM,Båvenholm P,Hamsten A

    更新日期:1995-03-14 00:00:00

  • 14-3-3 proteins associate with cdc25 phosphatases.

    abstract::The cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of...

    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.92.17.7892

    authors: Conklin DS,Galaktionov K,Beach D

    更新日期:1995-08-15 00:00:00

  • Cellular studies of auditory hair cell regeneration in birds.

    abstract::A decade ago it was discovered that mature birds are able to regenerate hair cells, the receptors for auditory perception. This surprising finding generated hope in the field of auditory neuroscience that new hair cells someday may be coaxed to form in another class of warm-blooded vertebrates, mammals. We have made c...

    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.97.22.11714

    authors: Stone JS,Rubel EW

    更新日期:2000-10-24 00:00:00

  • Neural correlates of behavior in the moth Manduca sexta in response to complex odors.

    abstract::With Manduca sexta as a model system, we analyzed how natural odor mixtures that are most effective in eliciting flight and foraging behaviors are encoded in the primary olfactory center in the brain, the antennal lobe. We used gas chromatography coupled with multiunit neural-ensemble recording to identify key odorant...

    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.0910592106

    authors: Riffell JA,Lei H,Hildebrand JG

    更新日期:2009-11-17 00:00:00

  • Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2.

    abstract::We have previously described how T and natural killer (NK) lineage commitment proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T/NK from unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The mol...

    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.091537598

    authors: Ikawa T,Fujimoto S,Kawamoto H,Katsura Y,Yokota Y

    更新日期:2001-04-24 00:00:00

  • Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection.

    abstract::Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. Current influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy. Although several bnAbs bind to the conserved stem domain of HA, focusing the immun...

    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.1402766111

    authors: Mallajosyula VV,Citron M,Ferrara F,Lu X,Callahan C,Heidecker GJ,Sarma SP,Flynn JA,Temperton NJ,Liang X,Varadarajan R

    更新日期:2014-06-24 00:00:00

  • A scheme for sequencing large DNA molecules by identifying local nuclear-induced effects.

    abstract::An experimental scheme for sequencing large DNA molecules is proposed where DNA strands are replicated, with all nucleotides of a given kind marked with radioactive 32P. The marked strands are affixed to an appropriate substrate and are kept until most 32P atoms decay. The local damage caused by the decay is expected ...

    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.91.15.6963

    authors: Kelson I,Nussinov S

    更新日期:1994-07-19 00:00:00