Characterization of the potent neuroprotective properties of the natural vitamin E alpha-tocotrienol.

Abstract:

:The natural vitamin E tocotrienols possess properties not shared by tocopherols. Nanomolar alpha-tocotrienol, not alpha-tocopherol, is potently neuroprotective. On a concentration basis, this finding represents the most potent of all biological functions exhibited by any natural vitamin E molecule. We sought to dissect the antioxidant-independent and -dependent neuroprotective properties of alpha-tocotrienol by using two different triggers of neurotoxicity, homocysteic acid (HCA) and linoleic acid. Both HCA and linoleic acid caused neurotoxicity with comparable features, such as increased ratio of oxidized to reduced glutathione GSSG/GSH, raised intracellular calcium concentration and compromised mitochondrial membrane potential. Mechanisms underlying HCA-induced neurodegeneration were comparable to those in the path implicated in glutamate-induced neurotoxicity. Inducible activation of c-Src and 12-lipoxygenase (12-Lox) represented early events in that pathway. Overexpression of active c-Src or 12-Lox sensitized cells to HCA-induced death. Nanomolar alpha-tocotrienol was protective. Knock-down of c-Src or 12-Lox attenuated HCA-induced neurotoxicity. Oxidative stress represented a late event in HCA-induced death. The observation that micromolar, but not nanomolar, alpha-tocotrienol functions as an antioxidant was verified in a model involving linoleic acid-induced oxidative stress and cell death. Oral supplementation of alpha-tocotrienol to humans results in a peak plasma concentration of 3 microm. Thus, oral alpha-tocotrienol may be neuroprotective by antioxidant-independent as well as antioxidant-dependent mechanisms.

journal_name

J Neurochem

authors

Khanna S,Roy S,Parinandi NL,Maurer M,Sen CK

doi

10.1111/j.1471-4159.2006.04000.x

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

1474-86

issue

5

eissn

0022-3042

issn

1471-4159

pii

JNC4000

journal_volume

98

pub_type

杂志文章
  • Metabolite changes in the cerebral cortex of treated and untreated infant hydrocephalic rats studied using in vitro 31P-NMR spectroscopy.

    abstract::The effect of hydrocephalus on cerebral energy metabolites and on intermediates of membrane phospholipid metabolism has been studied in H-Tx rats with inherited infantile hydrocephalus. Hydrocephalic rats and rats with shunts placed at 4-5 days or at 10 days after birth were subjected to magnetic resonance imaging in ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.67052030.x

    authors: Harris NG,Plant HD,Briggs RW,Jones HC

    更新日期:1996-11-01 00:00:00

  • Effects of choline and quiescence on Drosophila choline acetyltransferase expression and acetylcholine production by transduced rat fibroblasts.

    abstract::Rat-1 fibroblasts were transduced to express Drosophila choline acetyltransferase. The presence of an active enzyme in these cells (Rat-1/dChAT) was confirmed using various methods. Rat-1/dChAT fibroblasts released acetylcholine (ACh) into the culture medium. Moreover, intra- and extracellular levels of ACh could be i...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb10942.x

    authors: Schinstine M,Rosenberg MB,Routledge-Ward C,Friedmann T,Gage FH

    更新日期:1992-06-01 00:00:00

  • Expression of the glucagon-like peptide-1 receptor gene in rat brain.

    abstract::Evidence that glucagon-like peptide-1 (GLP-1) (7-36) amide functions as a novel neuropeptide prompted us to study the gene expression of its receptor in rat brain. Northern blot analysis showed transcripts of similar size in RINm5F cells, hypothalamus, and brain-stem. First-strand cDNA was prepared by using RNA from h...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.66030920.x

    authors: Alvarez E,Roncero I,Chowen JA,Thorens B,Blázquez E

    更新日期:1996-03-01 00:00:00

  • Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction.

    abstract::Mitochondrial dysfunction represents a critical event during the pathogenesis of Parkinson's disease (PD) and expanding evidences demonstrate that an altered balance in mitochondrial fission/fusion is likely an important mechanism leading to mitochondrial and neuronal dysfunction/degeneration. In this study, we invest...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2012.07734.x

    authors: Wang X,Petrie TG,Liu Y,Liu J,Fujioka H,Zhu X

    更新日期:2012-06-01 00:00:00

  • Metallothionein-III prevents glutamate and nitric oxide neurotoxicity in primary cultures of cerebellar neurons.

    abstract::Metallothionein (MT)-III, a member of the MT family of metal-binding proteins, is mainly expressed in the CNS and is abundant in glutamatergic neurons. Results in genetically altered mice indicate that MT-III may play neuroprotective roles in the brain, but the mechanisms through which this protein functions have not ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0750266.x

    authors: Montoliu C,Monfort P,Carrasco J,Palacios O,Capdevila M,Hidalgo J,Felipo V

    更新日期:2000-07-01 00:00:00

  • CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration.

    abstract::Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytos...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12684

    authors: Liman J,Deeg S,Voigt A,Voßfeldt H,Dohm CP,Karch A,Weishaupt J,Schulz JB,Bähr M,Kermer P

    更新日期:2014-06-01 00:00:00

  • Amyloid-β peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier.

    abstract::Amyloid-β peptide (Aβ) concentration in CSF is potentially a diagnostic and therapeutic target for Alzheimer's disease (AD). The purpose of this study was to clarify the elimination mechanism of human Aβ(1-40) [hAβ (1-40)] from CSF. After intracerebroventricular (ICV) administration, [(125) I]hAβ(1-40) was eliminated ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2011.07311.x

    authors: Fujiyoshi M,Tachikawa M,Ohtsuki S,Ito S,Uchida Y,Akanuma S,Kamiie J,Hashimoto T,Hosoya K,Iwatsubo T,Terasaki T

    更新日期:2011-08-01 00:00:00

  • A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease.

    abstract::Neurodegenerative diseases such as Alzheimer's disease (AD) are characterized by an abnormal aggregation of misfolded beta-sheet rich proteins such as β-amyloid (Aβ). Various ubiquitously expressed molecular chaperones control the correct folding of cellular proteins and prevent the accumulation of harmful species. We...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12454

    authors: Hoshino A,Helwig M,Rezaei S,Berridge C,Eriksen JL,Lindberg I

    更新日期:2014-02-01 00:00:00

  • Biogenic aldehydes in brain: characteristics of a reaction between rat brain tissue and indole-3-acetaldehyde.

    abstract::When indole-3-acetaldehyde was incubated with rat brain tissue, an aldehyde dehydrogenase-independent irreversible disappearance of the aldehyde was found. This was accompanied by an increase in absorbance at 240-400 nm, with a peak at 310 nm. The results suggested that this change in absorbance was caused by a membra...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1985.tb04055.x

    authors: Nilsson GE,Tottmar O

    更新日期:1985-09-01 00:00:00

  • Low-density lipoprotein receptor-related protein levels and endocytic function are reduced by overexpression of the FE65 adaptor protein, FE65L1.

    abstract::The FE65 adaptor protein family was identified in two-hybrid screens as proteins that bind the cytoplasmic domain of the amyloid precursor protein (APP). Studies have shown that FE65 binding to APP modulates APP processing. Increased levels of alpha-secretase derived secreted APP (APPsalpha) and beta-amyloid (Abeta) w...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2002.01009.x

    authors: Guénette SY,Chang Y,Hyman BT,Tanzi RE,Rebeck GW

    更新日期:2002-08-01 00:00:00

  • Chronic NMDA administration to rats up-regulates frontal cortex cytosolic phospholipase A2 and its transcription factor, activator protein-2.

    abstract::Excessive N-methyl-D-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms. Lithium and carbamazepine, effective against bipolar mania, are reported in rats to reduce brain transcription of an arachidonic acid selective calcium-dependent cytosolic phospholipase A(2) (cPLA(2)), as well as exp...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,收录出版

    doi:10.1111/j.1471-4159.2007.04648.x

    authors: Rao JS,Ertley RN,Rapoport SI,Bazinet RP,Lee HJ

    更新日期:2007-09-01 00:00:00

  • Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain.

    abstract::Microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated in affected neurons of Alzheimer disease brain. This hyperphosphorylated tau can be dephosphorylated at some of the abnormal phosphorylated sites by purified protein phosphatase-1, 2A, and 2B in vitro. In the present study, we have dev...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.65020732.x

    authors: Gong CX,Shaikh S,Wang JZ,Zaidi T,Grundke-Iqbal I,Iqbal K

    更新日期:1995-08-01 00:00:00

  • 3-Nitropropionic acid toxicity in the striatum.

    abstract::We examined the effects of chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in doses ranging from 12 to 16 mg/kg/day for 30 days on striatal cytoarchitecture in rats. Administration of 3-NP at a dose of 16 mg/kg/day resulted in large lesions with a central necrotic core that was ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.63051772.x

    authors: Wüllner U,Young AB,Penney JB,Beal MF

    更新日期:1994-11-01 00:00:00

  • Frame-shifted amyloid precursor protein found in Alzheimer's disease and Down's syndrome increases levels of secreted amyloid beta40.

    abstract::Frame-shifted amyloid precursor protein (APP(+1)), which has a truncated out-of-frame C-terminus, accumulates in the neuropathological hallmarks of patients with Alzheimer's disease pathology. To study a possible involvement of APP(+1) in the pathogenesis of Alzheimer's disease, we expressed APP695 and APP(+1) in the ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2004.02528.x

    authors: van Dijk R,Fischer DF,Sluijs JA,Sonnemans MA,Hobo B,Mercken L,Mann DM,Hol EM,van Leeuwen FW

    更新日期:2004-08-01 00:00:00

  • Sialylation enhances the secretion of neurotoxic amyloid-beta peptides.

    abstract::Alzheimer's disease (AD) is characterized by amyloid-beta peptide (Abeta) deposition in the brain. Abeta is produced by sequential cleavage of amyloid precursor protein (APP) by beta-secretase (BACE1: beta-site APP-cleaving enzyme 1) and gamma-secretase. Previously, we demonstrated that BACE1 also cleaves beta-galacto...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2005.03595.x

    authors: Nakagawa K,Kitazume S,Oka R,Maruyama K,Saido TC,Sato Y,Endo T,Hashimoto Y

    更新日期:2006-02-01 00:00:00

  • Galactosyltransferase defects in reeler mouse brains.

    abstract::Galactosyltransferase activities were examined in the cerebellum, cerebral cortex, and brain stem of reeler and wild-type mice. Galactosyltransferase assays were optimal for all required substrates, linear with incubation time, and proportional to protein concentration. In brain areas affected by the reeler mutation (...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1982.tb04719.x

    authors: Shur BD

    更新日期:1982-07-01 00:00:00

  • Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression.

    abstract::Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.13230

    authors: Hunsberger HC,Weitzner DS,Rudy CC,Hickman JE,Libell EM,Speer RR,Gerhardt GA,Reed MN

    更新日期:2015-10-01 00:00:00

  • IL-1 beta induces proMMP-9 expression via c-Src-dependent PDGFR/PI3K/Akt/p300 cascade in rat brain astrocytes.

    abstract::In a previous study, interleukin-1beta (IL-1beta) has been shown to induce matrix metalloproteinases (MMPs) expression through mitogen-activated protein kinases and nuclear factor-kappaB pathways in rat brain astrocytes. Moreover, transactivation of growth factor receptors and phosphatidylinositol 3-kinase (PI3K)/Akt ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2008.05318.x

    authors: Wu CY,Hsieh HL,Sun CC,Tseng CP,Yang CM

    更新日期:2008-05-01 00:00:00

  • Lipidomic profiling in mouse brain reveals differences between ages and genders, with smaller changes associated with alpha-synuclein genotype.

    abstract::Advances in lipidomics technology have facilitated the precise detection, identification and profiling of lipid species within tissues. Mass spectrometry allows for identification of lipids as a function of the total number of carbons and double bonds in their acyl chains. Such detailed descriptions of lipid compositi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2009.06290.x

    authors: Rappley I,Myers DS,Milne SB,Ivanova PT,Lavoie MJ,Brown HA,Selkoe DJ

    更新日期:2009-10-01 00:00:00

  • Interactions between vasoactive intestinal peptide and dopamine in the rabbit retina: stimulation of a common adenylate cyclase.

    abstract::Although 3,4-dihydroxyphenylethylamine (dopamine, DA) and vasoactive intestinal peptide (VIP) have been reported to stimulate adenylate cyclase activity in the rabbit retina, possible interactions between VIP-sensitive and DA-sensitive adenylate cyclase systems have not been previously investigated. To elucidate the i...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1986.tb12955.x

    authors: Pachter JA,Lam DM

    更新日期:1986-01-01 00:00:00

  • Reduced number of unmyelinated sensory axons in peripherin null mice.

    abstract::Peripherin is a type III intermediate filament (IF) abundantly expressed in developing neurons, but in the adult, it is primarily found in neurons extending to the peripheral nervous system. It has been suggested that peripherin may play a role in axonal elongation and/or cytoskeletal stabilization during development ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2002.00853.x

    authors: Larivière RC,Nguyen MD,Ribeiro-da-Silva A,Julien JP

    更新日期:2002-05-01 00:00:00

  • Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitors identify a novel calcium pool in the central nervous system.

    abstract::Ca2+ uptake into the endoplasmic reticulum (ER) is mediated by Ca2+ ATPase isoforms, which are all selectively inhibited by nanomolar concentrations of thapsigargin. Using ATP/Mg2+-dependent 45Ca2+ transport in rat brain microsomes, tissue sections, and permeabilized cells, as well as Ca2+ imaging in living cells we d...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2003.01962.x

    authors: Watson WD,Facchina SL,Grimaldi M,Verma A

    更新日期:2003-10-01 00:00:00

  • Glycerol phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase: activities in oligodendrocytes, neurons, astrocytes, and myelin isolated from developing rat brains.

    abstract::Glycerol phosphate dehydrogenase (GPDH), glucose-6-phosphate dehydrogenase (G6PDH), and lactate dehydrogenase (LDH) activities were determined in oligodendrocytes, neurons, and astrocytes isolated from the brains of developing rats. The activity of each enzyme was significantly lower in both neurons and astrocytes tha...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1982.tb08637.x

    authors: Cammer W,Snyder DS,Zimmerman TR Jr,Farooq M,Norton WT

    更新日期:1982-02-01 00:00:00

  • Essential role for integrin linked kinase in Akt-mediated integrin survival signaling in hippocampal neurons.

    abstract::Activation of integrin receptors in neurons can promote cell survival and synaptic plasticity, but the underlying signal transduction pathway(s) is unknown. We report that integrin signaling prevents apoptosis of embryonic hippocampal neurons by a mechanism involving integrin-linked kinase (ILK) that activates Akt kin...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2003.01579.x

    authors: Gary DS,Milhavet O,Camandola S,Mattson MP

    更新日期:2003-02-01 00:00:00

  • Glutamate inhibition of the adrenergic-stimulated production of melatonin in rat pineal gland in vitro.

    abstract::The effect of L-glutamate on the adrenergic-stimulated release of melatonin in the rat pineal gland was examined using an in vitro perfusion system. L-Glutamate by itself had no effect on melatonin secretion whereas L-glutamate administered prior to (-)-isoproterenol (beta-adrenergic agonist) and L-phenylephrine (alph...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.62062241.x

    authors: Kus L,Handa RJ,McNulty JA

    更新日期:1994-06-01 00:00:00

  • Secretory proteins from adrenal medullary cells are carboxyl-methylated in vivo and released under their methylated form by acetylcholine.

    abstract::The carboxyl methylation of secretory proteins in vivo was investigated in bovine adrenal medullary cells in culture. Chromogranin A, the major intragranular secretory protein in adrenal medullary cells, and other secretory proteins were found to be carboxyl-methylated within secretory vesicles. The in vivo labeling p...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1987.tb03391.x

    authors: Nguyen MH,Harbour D,Gagnon C

    更新日期:1987-07-01 00:00:00

  • The endocannabinoid system in the brain of Carassius auratus and its possible role in the control of food intake.

    abstract::Cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoylglycerol have been suggested to regulate food intake in several animal phyla. Orthologs of the mammalian cannabinoid CB(1) and CB(2) receptors have been identified in fish. We investigated the presence of this endocannabinoid system in the bra...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2005.03406.x

    authors: Valenti M,Cottone E,Martinez R,De Pedro N,Rubio M,Viveros MP,Franzoni MF,Delgado MJ,Di Marzo V

    更新日期:2005-11-01 00:00:00

  • Biogenesis of presynaptic terminal proteins.

    abstract::The delivery of proteins to the presynaptic terminals of guinea pig retinal ganglion cells by two of the major components of axonal transport, and the subsequent persistence and turnover of those proteins were examined in this study. Ganglion cell proteins were radiolabeled by intravitreal injection of radiolabeled am...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1987.tb00979.x

    authors: Garner JA,Mahler HR

    更新日期:1987-09-01 00:00:00

  • Amyloid Abeta1-40 preconditions non-apoptotic signals in vivo and protects fetal rat brain from intrauterine ischemic stress.

    abstract::Abstract The dualistic activities of the amyloid beta (Abeta) peptide as a pro-oxidant and ubiquitous constituent of amyloid deposits in Alzheimer's disease plaques and as an antioxidant of purported physiological function has been suggested but the mechanisms are far from being understood. In this report we measure s...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2004.02778.x

    authors: Kuperstein F,Brand A,Yavin E

    更新日期:2004-11-01 00:00:00

  • Characterization and comparison of neurofilament proteins from rat and mouse CNS.

    abstract::Rat and mouse CNS neurofilament proteins (NFPs) were characterized and compared, in terms of electrophoretic properties on polyacrylamide gels and by peptide mapping, with one another and with other co-purifying lower-molecular-weight CNS proteins, including alpha and beta tubulin. NFPs were partially purified by modi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb02389.x

    authors: Brown BA,Nixon RA,Strocchi P,Marotta CA

    更新日期:1981-01-01 00:00:00