Selective linkage of mitochondrial enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.


:Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key mitochondrial enzyme complex, is diminished in brains from AD patients, and can be plausibly linked to plaques and tangles. Our previous studies in cell lines and mouse neurons demonstrate that reductions in KGDHC increase the ER releasable calcium stores. The goal of these studies was to test whether the relationship was true in human iPSC-derived neurons. Inhibition of KGDHC for one or 24 hr increased the ER releasable calcium store in human neurons by 69% and 144%, respectively. The effect was mitochondrial enzyme specific because inhibiting the pyruvate dehydrogenase complex, another key mitochondrial enzyme complex, diminished the ER releasable calcium stores. The link of KGDHC to ER releasable calcium stores was cell type specific as the interaction was not present in iPSC or neural stem cells. Thus, these studies in human neurons verify a link between KGDHC and releasable ER calcium stores, and support the use of human neurons to examine mechanisms and potential therapies for AD.


J Neurochem


Chen H,Cross AC,Thakkar A,Xu H,Li A,Paull D,Noggle SA,Kruger L,Denton TT,Gibson GE




Has Abstract


2020-08-31 00:00:00






  • 2-Amino-7-phosphonoheptanoic acid inhibits insulin-induced convulsions and striatal aspartate accumulation in rats with frontal cortical ablation.

    abstract::Pretreatment of rats with the excitatory amino acid antagonist 2-amino-7-phosphonoheptanoic acid (2-APH; 0.5 mmol/kg, i.p.) protected against insulin-induced clonic seizures. Complete protection was observed in 38% of the rats and partial protection in an additional 50%. Lesioning of the corticostriatal pathway by fro...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Chapman AG,Engelsen B,Meldrum BS

    更新日期:1987-07-01 00:00:00

  • Allelic variation of human serotonin transporter gene expression.

    abstract::Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5-HT) system. By directing the magnitude and duration of postsynaptic responses, carrier-facilitated 5-HT transport into...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Heils A,Teufel A,Petri S,Stöber G,Riederer P,Bengel D,Lesch KP

    更新日期:1996-06-01 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


    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

  • Genomic effects of cold and isolation stress on magnocellular vasopressin mRNA-containing cells in the hypothalamus of the rat.

    abstract::We assessed the effects of cold and isolation stress on arginine vasopressin (AVP) mRNA in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Vasopressin mRNA levels were determined by in situ hybridization histochemistry at the cellular level. In posterior magnocellular neurons of the PVN isol...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Angulo JA,Ledoux M,McEwen BS

    更新日期:1991-06-01 00:00:00

  • Effects of picrotoxin treatment on GABAA receptor supramolecular complexes in rat brain.

    abstract::The effects of acute and chronic administration of a subconvulsive dose of picrotoxin on t-[35S]butylbicyclophosphorothionate ([3S]TBPS), [3H]muscimol, and [3H]flunitrazepam binding characteristics in various regions and on the convulsant potency of picrotoxin in Sprague-Dawley rats were examined. Acute administration...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Ito Y,Lim DK,Nabeshima T,Ho IK

    更新日期:1989-04-01 00:00:00

  • Glutamate dehydrogenase reaction as a source of glutamic acid in synaptosomes.

    abstract::The role of the glutamate dehydrogenase reaction as a pathway of glutamate synthesis was studied by incubating synaptosomes with 5 mM 15NH4Cl and then utilizing gas chromatography-mass spectrometry to measure isotopic enrichment in glutamate and aspartate. The rate of formation of [15N]glutamate and [15N]aspartate fro...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Yudkoff M,Nissim I,Nelson D,Lin ZP,Erecińska M

    更新日期:1991-07-01 00:00:00

  • Central cholinergic function and metabolic changes in streptozotocin-induced rat brain injury.

    abstract::As glucose hypometabolism in the brain is an early sign of Alzheimer´s dementia (AD), the diabetogenic drug streptozotocin (STZ) has been used to induce Alzheimer-like pathology in rat brain by intracereboventricular injection (icv-STZ). However, many details of the pathological mechanism of STZ in this AD model remai...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Yuliani T,Lobentanzer S,Klein J

    更新日期:2020-08-16 00:00:00

  • Guanine nucleotide regulatory proteins, Gq and Gi1/2, mediate platelet-activating factor-stimulated phosphoinositide metabolism in immortalized hippocampal cells.

    abstract::Platelet-activating factor (PAF) may be a neuromodulator involved in neural cell differentiation, cerebral inflammation, and ischemia. The PAF receptor is a member of the G protein-coupled receptor superfamily. In the present study, we sought to define the specific G protein(s) that mediate PAF-stimulated phosphoinosi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Shi LC,Wang HY,Horwitz J,Friedman E

    更新日期:1996-10-01 00:00:00

  • Bone morphogenetic protein down-regulation of neuronal pituitary adenylate cyclase-activating polypeptide and reciprocal effects on vasoactive intestinal peptide expression.

    abstract::Among bone morphogenetic proteins (BMPs), the decapentaplegic (Dpp; BMP2, BMP4) and glass bottom boat (Gbb/60A; BMP5, BMP6, BMP7) subgroups have well-described functions guiding autonomic and sensory neuronal development, fiber formation and neurophenotypic identities. Evaluation of rat superior cervical ganglia (SCG)...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Pavelock KA,Girard BM,Schutz KC,Braas KM,May V

    更新日期:2007-02-01 00:00:00

  • Muscarinic toxins: tools for the study of the pharmacological and functional properties of muscarinic receptors.

    abstract::Muscarinic receptors mediate metabotropic actions of acetylcholine in the CNS and PNS and autocrine functions of acetylcholine in non-neuronal systems. Because of the lack of highly selective muscarinic ligands, the precise location, functional role, and roles in various diseases of the five muscarinic receptor subtyp...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审


    authors: Servent D,Fruchart-Gaillard C

    更新日期:2009-06-01 00:00:00

  • Stimulation of the serotonin autoreceptor prevents the calcium-calmodulin-dependent increase of serotonin biosynthesis in rat raphe slices.

    abstract::The role of the serotonin (5-hydroxytryptamine) autoreceptor in the regulation of the activity of tryptophan hydroxylase was investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measuring the accumulation of 5-hydroxytryptophan in the presence of inhibition of aromatic L-amino acid...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Sawada M,Nagatsu T

    更新日期:1986-03-01 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


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

    更新日期:2002-08-01 00:00:00

  • Involvement of metabotropic glutamate receptor 5 in the inhibition of methamphetamine-associated contextual memory after prolonged extinction training.

    abstract::Addiction is thought to be a memory process between perception and environmental cues and addicted patients often relapse when they come into contact with the drug-related context once again. Here, we used a conditioned place preference protocol to seek a more effective extinction methodology of methamphetamine (METH)...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Huang CH,Yu YJ,Chang CH,Gean PW

    更新日期:2016-04-01 00:00:00

  • The effect of Cyclin-dependent kinase 5 on voltage-dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state.

    abstract::Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre-synaptic terminals triggered by Ca(2+) influx into the pre-synaptic cytoplasm through voltage-dependent Ca(2+) channels (VDCCs). It is reported that Cdk5 regulates L-, P/Q-, or N-type VDCC, but...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Furusawa K,Asada A,Saito T,Hisanaga S

    更新日期:2014-08-01 00:00:00

  • Neuronal protection by sirtuins in Alzheimer's disease.

    abstract::Silent information regulator 2, a member of NAD+-dependent histone deacetylase in yeast, and its homologs in mice and humans, participate in numerous important cell functions, including cell protection and cell cycle regulation. The sirtuin family members are highly conserved evolutionarily, and are predicted to have ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审


    authors: Anekonda TS,Reddy PH

    更新日期:2006-01-01 00:00:00

  • 1-Benzyl-1,2,3,4-tetrahydroisoquinoline binds with tubulin beta, a substrate of parkin, and reduces its polyubiquitination.

    abstract::Substances that mimic the actions of causative gene products of familial Parkinson's disease (PD) are candidate as causative agents of idiopathic PD. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is present at three times higher levels in CSF of PD patients than in CSF of control subjects...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kohta R,Kotake Y,Hosoya T,Hiramatsu T,Otsubo Y,Koyama H,Hirokane Y,Yokoyama Y,Ikeshoji H,Oofusa K,Suzuki M,Ohta S

    更新日期:2010-09-01 00:00:00

  • Characterization of neurotransmitter receptors in the rat hippocampal formation.

    abstract::The hippocampal formation has been extensively research in terms of its putative neurotransmitters, anatomical connections, and behavioral relevance. An aspect of importance is the assessment of apparent neurotransmitter receptors by using receptor binding assays. In the present study, such assays were done in vitro t...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Dooley DJ,Bittiger H

    更新日期:1982-06-01 00:00:00

  • Differential involvement of central and peripheral norepinephrine in the central lipopolysaccharide-induced interleukin-6 responses in mice.

    abstract::Intracerebroventricular injection of lipopolysaccharide (LPS) induces a marked increase in circulating interleukin (IL)-6 levels and in IL-6 mRNA expression in brain and peripheral organs. Recently, it was reported that intraperitoneal administration of alpha-adrenoceptor antagonists inhibits centrally injected LPS-in...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Song DK,Im YB,Jung JS,Suh HW,Huh SO,Park SW,Wie MB,Kim YH

    更新日期:1999-04-01 00:00:00

  • Effects of organotins on rat brain astrocytes in culture.

    abstract::The interaction of triethyltin (TET) and trimethyltin (TMT) with rat brain astrocytes in vitro was investigated. Both compounds are highly neurotoxic after in vivo application, cause neurobehavioral changes, and elicit neuronal and glial responses in the CNS. In this study, 5-week-old cultures were exposed to TMT or T...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Richter-Landsberg C,Besser A

    更新日期:1994-12-01 00:00:00

  • Inhibitors of histamine methylation in brain promote formation of imidazoleacetic acid, which interacts with GABA receptors.

    abstract::In brain, the precursor of imidazoleacetic acid (IAA), a GABAA agonist but a GABAC antagonist, is not known. In the periphery, IAA derives from oxidation of histamine. But in brain, histamine is thought to be metabolized solely by histamine methyltransferase (HMT), forming tele-methylhistamine (t-MH) and tele-methylim...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Prell GD,Morrishow AM,Duoyon E,Lee WS

    更新日期:1997-01-01 00:00:00

  • Role of calmodulin and protein kinase C in astrocytic cell volume regulation.

    abstract::We investigated the role of Ca(2+)-dependent protein kinases in the regulation of astrocytic cell volume. Calmodulin (CaM) antagonists were used to inhibit CaM and thus Ca2+/CaM-dependent protein kinase. The effect of these inhibitors as well as activators and inhibitors of protein kinase C (PKC) on astrocytic volume ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Bender AS,Neary JT,Blicharska J,Norenberg LO,Norenberg MD

    更新日期:1992-05-01 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


    authors: Nguyen MH,Harbour D,Gagnon C

    更新日期:1987-07-01 00:00:00

  • Changes in NMDA receptor subunit expression in response to contusive spinal cord injury.

    abstract::Differential assembly of N-methyl-D-aspartate (NMDA) receptor subunits determines their functional characteristics. Using in situ hybridization, we found a selective increase of the subunits NR1 and NR2A mRNA at 24 h in ventral motor neurons (VMN) caudal to a standardized spinal cord contusion injury (SCI). Other neur...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Grossman SD,Wolfe BB,Yasuda RP,Wrathall JR

    更新日期:2000-07-01 00:00:00

  • Different roles for Gi and Go proteins in modulation of adenylyl cyclase type-2 activity.

    abstract::The effect of Gi/o protein-coupled receptors on adenylyl cyclase type 2 (AC2) has been studied in Sf9 insect cells. Stimulation of cells expressing AC2 with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) led to a twofold stimulation of cAMP synthesis that could be blocked with the protein kinase C inhib...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Näsman J,Kukkonen JP,Holmqvist T,Akerman KE

    更新日期:2002-12-01 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


    authors: Kuperstein F,Brand A,Yavin E

    更新日期:2004-11-01 00:00:00

  • A UDP-sugar pyrophosphatase is developmentally regulated in the rat retina.

    abstract::Rat retina tissue contains relatively high amounts of GD3 in relation to ganglio-series gangliosides even in the adult stages. This was attributed in part to an activity ratio between the enzyme that converts GM3 to GD3 [sialytransferase II (ST-II)] and the enzyme that converts GM3 to GM2 [N-acetylgalactosaminyltransf...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Martina JA,Daniotti JL,Maccioni HJ

    更新日期:1995-03-01 00:00:00

  • Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons.

    abstract::Deep hypothermia protects the brain from ischemic damage and is therefore used during major cardiovascular surgeries requiring cardiopulmonary bypass and a period of circulatory arrest. Here, we demonstrated that small ubiquitin-like modifier (SUMO1-3) conjugation is markedly activated in the brain during deep to mode...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Wang L,Ma Q,Yang W,Mackensen GB,Paschen W

    更新日期:2012-11-01 00:00:00

  • Effects of chronic ethanol consumption and aging on dopamine, serotonin, and metabolites.

    abstract::This study examined the hypothesis that chronic ethanol consumption results in significant abnormalities in both the dopaminergic and the serotonergic system of aged rats. Levels of dopamine (DA), serotonin [5-hydroxytryptamine (5-HT)], 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindole-3-acetic acid (5-HIAA)...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Woods JM,Druse MJ

    更新日期:1996-05-01 00:00:00

  • Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71.

    abstract::Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control brain, suggestin...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Castegna A,Aksenov M,Thongboonkerd V,Klein JB,Pierce WM,Booze R,Markesbery WR,Butterfield DA

    更新日期:2002-09-01 00:00:00

  • Characterization of quinolinic acid phosphoribosyltransferase in human blood and observations in Huntington's disease.

    abstract::Quinolinic acid (QUIN), an excitotoxic compound present in the mammalian CNS and periphery, has been hypothetically linked to human neurodegenerative disorders such as Huntington's disease and epilepsy. Quinolinic acid phosphoribosyltransferase (QPRT), the catabolic enzyme of QUIN, is found in the CNS and peripheral o...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Foster AC,Schwarcz R

    更新日期:1985-07-01 00:00:00