Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity.

Abstract:

:NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent neuroprotective protein, is protective at femtomolar concentrations against a wide array of neural insults and prevents ethanol-induced fetal wastage and growth retardation in mice. NAP also antagonizes ethanol inhibition of L1-mediated cell adhesion (ethanol antagonism). We performed an Ala scanning substitution of NAP to determine the role of ethanol antagonism and neuroprotection in NAP prevention of ethanol embryotoxicity. The Ser-Ile-Pro region of NAP was crucial for both ethanol antagonism and protection of cortical neurons from tetrodotoxin toxicity (neuroprotection). Ala replacement of either Ser-5 or Pro-7 (P7A-NAP) abolished NAP neuroprotection but minimally changed the efficacy of NAP ethanol antagonism. In contrast, Ala replacement of Ile-6 (I6A-NAP) caused a decrease in potency (>2 logarithmic orders) with only a small reduction (<10%) in the efficacy of NAP neuroprotection but markedly reduced the efficacy (50%) and the potency (5 logarithmic orders) of NAP ethanol antagonism. Ethanol significantly reduced the number of paired somites in mouse whole-embryo culture; this effect was prevented significantly by 100 pM NAP or by 100 pM P7A-NAP, but not by 100 pM I6A-NAP. The structure-activity relation for NAP prevention of ethanol embryotoxicity was similar to that for NAP ethanol antagonism and different from that for NAP neuroprotection. These findings support the hypothesis that NAP antagonism of ethanol inhibition of L1 adhesion plays a central role in NAP prevention of ethanol embryotoxicity and highlight the potential importance of ethanol effects on L1 in the pathophysiology of fetal alcohol syndrome.

authors

Wilkemeyer MF,Chen SY,Menkari CE,Brenneman DE,Sulik KK,Charness ME

doi

10.1073/pnas.1331636100

keywords:

subject

Has Abstract

pub_date

2003-07-08 00:00:00

pages

8543-8

issue

14

eissn

0027-8424

issn

1091-6490

pii

1331636100

journal_volume

100

pub_type

杂志文章
  • Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complex.

    abstract::A great deal is known about the export of spliced mRNAs, but little is known about the export of mRNAs encoded by human cellular genes that naturally lack introns. Here, we investigated the requirements for export of three naturally intronless mRNAs (HSPB3, IFN-α1, and IFN-β1). Significantly, we found that all three m...

    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.1113076108

    authors: Lei H,Dias AP,Reed R

    更新日期:2011-11-01 00:00:00

  • Neurotrophic activity of platelet-derived growth factor (PDGF): Rat neuronal cells possess functional PDGF beta-type receptors and respond to PDGF.

    abstract::The different isoforms of PDGF bind with different affinities to two different receptor types. Previously, these receptors have been demonstrated mainly on mesenchymal and glial cells. We show here that PDGF beta-type receptors are present also on rat brain neurons in vivo as well as in vitro. Immunohistochemical anal...

    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.88.18.8159

    authors: Smits A,Kato M,Westermark B,Nistér M,Heldin CH,Funa K

    更新日期:1991-09-15 00:00:00

  • The Mycobacterium tuberculosis Pup-proteasome system regulates nitrate metabolism through an essential protein quality control pathway.

    abstract::The human pathogen Mycobacterium tuberculosis encodes a proteasome that carries out regulated degradation of bacterial proteins. It has been proposed that the proteasome contributes to nitrogen metabolism in M. tuberculosis, although this hypothesis had not been tested. Upon assessing M. tuberculosis growth in several...

    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.1819468116

    authors: Becker SH,Jastrab JB,Dhabaria A,Chaton CT,Rush JS,Korotkov KV,Ueberheide B,Darwin KH

    更新日期:2019-02-19 00:00:00

  • Altered myelopoiesis and the development of acute myeloid leukemia in transgenic mice overexpressing cyclin A1.

    abstract::A mammalian A-type cyclin, cyclin A1, is highly expressed in testes of both human and mouse and targeted mutagenesis in the mouse has revealed the unique requirement for cyclin A1 in the progression of male germ cells through the meiotic cell cycle. While very low levels of cyclin A1 have been reported in the human he...

    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.121540098

    authors: Liao C,Wang XY,Wei HQ,Li SQ,Merghoub T,Pandolfi PP,Wolgemuth DJ

    更新日期:2001-06-05 00:00:00

  • Human-caused environmental change: impacts on plant diversity and evolution.

    abstract::Human-caused environmental changes are creating regional combinations of environmental conditions that, within the next 50 to 100 years, may fall outside the envelope within which many of the terrestrial plants of a region evolved. These environmental modifications might become a greater cause of global species extinc...

    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.091093198

    authors: Tilman D,Lehman C

    更新日期:2001-05-08 00:00:00

  • Hydrophobic ion transfer between membranes of adjacent hepatocytes: a possible probe of tight junction structure.

    abstract::The topology of the tight junction is probed by introducing dipicrylamine (dpa-), a lipid-soluble anion, into the membranes of hepatocyte pairs in culture. Once partitioned into the membrane, dpa- ions are free to move in the hydrophobic core of the membrane, where their mobile charges greatly increase membrane capaci...

    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.88.20.9365

    authors: Turin L,Béhé P,Plonsky I,Dunina-Barkovskaya A

    更新日期:1991-10-15 00:00:00

  • Symmetry in chemistry from the hydrogen atom to proteins.

    abstract::The last 2 decades have seen discoveries in highly excited states of atoms and molecules of phenomena that are qualitatively different from the "planetary" model of the atom, and the near-rigid model of molecules, characteristic of these systems in their low-energy states. A unified view is emerging in terms of approx...

    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.93.25.14287

    authors: Kellman ME

    更新日期:1996-12-10 00:00:00

  • Control of transient, resurgent, and persistent current by open-channel block by Na channel beta4 in cultured cerebellar granule neurons.

    abstract::Voltage-gated Na channels in several classes of neurons, including cells of the cerebellum, are subject to an open-channel block and unblock by an endogenous protein. The Na(V)beta4 (Scn4b) subunit is a candidate blocking protein because a free peptide from its cytoplasmic tail, the beta4 peptide, can block open Na ch...

    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.1005633107

    authors: Bant JS,Raman IM

    更新日期:2010-07-06 00:00:00

  • GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers.

    abstract::Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regul...

    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.1700465115

    authors: Kim S,Yun SP,Lee S,Umanah GE,Bandaru VVR,Yin X,Rhee P,Karuppagounder SS,Kwon SH,Lee H,Mao X,Kim D,Pandey A,Lee G,Dawson VL,Dawson TM,Ko HS

    更新日期:2018-01-23 00:00:00

  • Interfacial photoreactions and chemical capacitance in lipid bilayers.

    abstract::The electrical response of a pigmented lipid bilayer to a short laser pulse is measured by a tunable voltage clamp method. In this method, a variable access impedance permits "tuning" of the observed relaxations for optimal measurements. Analysis of the data so obtained leads to an equivalent circuit that contains a n...

    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.71.4.1564

    authors: Hong FT,Mauzerall D

    更新日期:1974-04-01 00:00:00

  • A helical-dipole model describes the single-channel current rectification of an uncharged peptide ion channel.

    abstract::We are designing simple peptide ion channels as model systems for the study of the physical principles controlling conduction through ion-channel proteins. Here we report on an uncharged peptide, Ac-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, designed to form an aggregate of parallel, amphiphilic, membrane-spanning alpha-he...

    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.91.11.4859

    authors: Kienker PK,DeGrado WF,Lear JD

    更新日期:1994-05-24 00:00:00

  • Porcine pituitary dynorphin: complete amino acid sequence of the biologically active heptadecapeptide.

    abstract::The full primary structure of the very potent opioid peptide dynorphin, from porcine pituitary, has been determined. It is (H)Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln(OH). The synthetic peptide with this sequence behaves identically to natural dynorphin in a number of ways, and it has the sa...

    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.78.11.7219

    authors: Goldstein A,Fischli W,Lowney LI,Hunkapiller M,Hood L

    更新日期:1981-11-01 00:00:00

  • Mechanical control of mitotic progression in single animal cells.

    abstract::Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedback-controlled confinement of single cells w...

    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.1502029112

    authors: Cattin CJ,Düggelin M,Martinez-Martin D,Gerber C,Müller DJ,Stewart MP

    更新日期:2015-09-08 00:00:00

  • The gene regulatory program of Acrobeloides nanus reveals conservation of phylum-specific expression.

    abstract::The evolution of development has been studied through the lens of gene regulation by examining either closely related species or extremely distant animals of different phyla. In nematodes, detailed cell- and stage-specific expression analyses are focused on the model Caenorhabditis elegans, in part leading to the view...

    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.1720817115

    authors: Schiffer PH,Polsky AL,Cole AG,Camps JIR,Kroiher M,Silver DH,Grishkevich V,Anavy L,Koutsovoulos G,Hashimshony T,Yanai I

    更新日期:2018-04-24 00:00:00

  • Evidence for secretory pathway localization of a voltage-dependent anion channel isoform.

    abstract::Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. Ho...

    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.060242297

    authors: Buettner R,Papoutsoglou G,Scemes E,Spray DC,Dermietzel R

    更新日期:2000-03-28 00:00:00

  • Structure of the Leanyer orthobunyavirus nucleoprotein-RNA complex reveals unique architecture for RNA encapsidation.

    abstract::Negative-stranded RNA viruses cover their genome with nucleoprotein (N) to protect it from the human innate immune system. Abrogation of the function of N offers a unique opportunity to combat the spread of the viruses. Here, we describe a unique fold of N from Leanyer virus (LEAV, Orthobunyavirus genus, Bunyaviridae ...

    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.1300035110

    authors: Niu F,Shaw N,Wang YE,Jiao L,Ding W,Li X,Zhu P,Upur H,Ouyang S,Cheng G,Liu ZJ

    更新日期:2013-05-28 00:00:00

  • Molecular mass, biochemical composition, and physicochemical behavior of the infectious form of the scrapie precursor protein monomer.

    abstract::A highly purified fraction obtained from scrapie (263-K strain)-infected hamsters' brains by an alternative procedure without proteinase K treatment contained a protease-resistant form of the scrapie precursor protein (PrPSc) and infectivity of 9.9 +/- 0.7 log LD50/ml. Polyclonal antibodies produced against hamster sc...

    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.87.16.6373

    authors: Safar J,Wang W,Padgett MP,Ceroni M,Piccardo P,Zopf D,Gajdusek DC,Gibbs CJ Jr

    更新日期:1990-08-01 00:00:00

  • Genotypic variation within asexual lineages of Taraxacum officinale.

    abstract::Restriction site variation in DNA that encodes rRNA (rDNA) was surveyed among 714 offspring within 31 lineages (26 genotypes) of obligate asexually reproducing Taraxacum officinale (dandelions). Although clonal offspring are expected, plants with nonparental rDNA were produced from two parents that were themselves sib...

    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.87.3.998

    authors: King LM,Schaal BA

    更新日期:1990-02-01 00:00:00

  • Phonon Green's function.

    abstract::The concepts of source and quantum action principle are used to produce the phonon Green's function appropriate for an initial phonon vacuum state. An application to the Mossbauer effect is presented. ...

    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.88.15.6537

    authors: Schwinger J

    更新日期:1991-08-01 00:00:00

  • Designing safer chemicals: predicting the rates of metabolism of halogenated alkanes.

    abstract::A computational model is presented that can be used as a tool in the design of safer chemicals. This model predicts the rate of hydrogen-atom abstraction by cytochrome P450 enzymes. Excellent correlations between biotransformation rates and the calculated activation energies (delta Hact) of the cytochrome P450-mediate...

    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.92.24.11076

    authors: Yin H,Anders MW,Korzekwa KR,Higgins L,Thummel KE,Kharasch ED,Jones JP

    更新日期:1995-11-21 00:00:00

  • Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model.

    abstract::Among the earliest and most important stages during tumorigenesis is the activation of the angiogenic process, an event that is termed the "switch to the angiogenic phenotype." We have developed an in vivo system that can reliably recapitulate the stages in tumor development that represent this transition. Using this ...

    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.97.8.3884

    authors: Fang J,Shing Y,Wiederschain D,Yan L,Butterfield C,Jackson G,Harper J,Tamvakopoulos G,Moses MA

    更新日期:2000-04-11 00:00:00

  • Two CD95 tumor classes with different sensitivities to antitumor drugs.

    abstract::CD95 type I and II cells differ in their dependence on mitochondria to execute apoptosis, because antiapoptotic members of the Bcl-2 family render only type II cells resistant to death receptor-induced apoptosis. They can also be distinguished by a more efficient formation of the death-inducing signaling complex in ty...

    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.2034995100

    authors: Algeciras-Schimnich A,Pietras EM,Barnhart BC,Legembre P,Vijayan S,Holbeck SL,Peter ME

    更新日期:2003-09-30 00:00:00

  • Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation.

    abstract::The circadian clock in eukaryotes controls transcriptional and posttranscriptional events, including regulation of the levels and phosphorylation state of translation factors. However, the mechanisms underlying clock control of translation initiation, and the impact of this potential regulation on rhythmic protein syn...

    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.1918459117

    authors: Karki S,Castillo K,Ding Z,Kerr O,Lamb TM,Wu C,Sachs MS,Bell-Pedersen D

    更新日期:2020-05-19 00:00:00

  • Recombination involving transposable elements: role of target molecule replication in Tn1 delta Ap-mediated replicon fusion.

    abstract::Donor DNA molecules carrying Tn1 or Tn3 deletion mutants do not need to replicate in order to participate in replicon fusion recombination events during which the Tn1/Tn3 element is duplicated. We have assayed Tn1 delta Ap-mediated replicon fusion events involving plasmid R388 and the bacteriophage lambda-derived plas...

    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.80.8.2314

    authors: Muster CJ,Shapiro JA,MacHattie LA

    更新日期:1983-04-01 00:00:00

  • Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex.

    abstract::Mutations of von Hippel-Lindau disease (VHL) tumor-suppressor gene product (pVHL) are found in patients with dominant inherited VHL syndrome and in the vast majority of sporadic clear cell renal carcinomas. The function of the pVHL protein has not been clarified. pVHL has been shown to form a complex with elongin B an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 评论,杂志文章

    doi:10.1073/pnas.96.22.12436

    authors: Iwai K,Yamanaka K,Kamura T,Minato N,Conaway RC,Conaway JW,Klausner RD,Pause A

    更新日期:1999-10-26 00:00:00

  • Reburn severity in managed and unmanaged vegetation in a large wildfire.

    abstract::Debate over the influence of postwildfire management on future fire severity is occurring in the absence of empirical studies. We used satellite data, government agency records, and aerial photography to examine a forest landscape in southwest Oregon that burned in 1987 and then was subject, in part, to salvage-loggin...

    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.0700229104

    authors: Thompson JR,Spies TA,Ganio LM

    更新日期:2007-06-19 00:00:00

  • Exo-endocytosis and closing of the fission pore during endocytosis in single pituitary nerve terminals internally perfused with high calcium concentrations.

    abstract::An increase in free Ca2+ triggers exocytosis in pituitary nerve terminals leading to an increase in membrane area and membrane capacitance. When Ca2+ is increased by step depolarization, an instantaneous capacitance increase during the first 80 ms is followed by a slow increase extending over several seconds. We measu...

    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.91.12.5267

    authors: Rosenboom H,Lindau M

    更新日期:1994-06-07 00:00:00

  • A JAK-STAT pathway regulates wing vein formation in Drosophila.

    abstract::We present evidence that the JAK-STAT signal transduction pathway regulates multiple developmental processes in Drosophila. We screened for second-site mutations that suppress the phenotype of the hyperactive hopTum-1 Jak kinase, and recovered a mutation that meiotically maps to the known chromosomal position of D-Sta...

    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.93.12.5842

    authors: Yan R,Luo H,Darnell JE Jr,Dearolf CR

    更新日期:1996-06-11 00:00:00

  • Modification of DNA ends can decrease end joining relative to homologous recombination in mammalian cells.

    abstract::In animal cells, exogenous DNA recombines into random chromosomal sites much more frequently than it recombines into homologous sites. Free DNA ends are "recombinogenic" in both processes. To test the effects of specific ends on analogous extrachromosomal processes, we constructed a linear genome of simian virus 40 wi...

    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.84.14.4959

    authors: Chang XB,Wilson JH

    更新日期:1987-07-01 00:00:00

  • Dysregulation of signaling pathways in CD45-deficient NK cells leads to differentially regulated cytotoxicity and cytokine production.

    abstract::CD45, a protein tyrosine phosphatase that regulates Src family kinases, is important for regulating T cell and B cell receptor signaling; however, little is known about how CD45 regulates immunoreceptor tyrosine-based activation motif (ITAM)-dependent natural killer (NK) cell receptor signaling and the resulting effec...

    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.0601851103

    authors: Hesslein DG,Takaki R,Hermiston ML,Weiss A,Lanier LL

    更新日期:2006-05-02 00:00:00