Unregulated mitochondrial GSK3beta activity results in NADH: ubiquinone oxidoreductase deficiency.

Abstract:

:GSK3beta is prominent for its role in apoptosis signaling and has been shown to be involved in Parkinson's disease (PD) pathogenesis. The overall effects of GSK3beta activity on cell fate are well-established, but the effects of mitochondrial GSK3beta activity on mitochondrial function and cell fate are unknown. Here we selectively expressed constitutively active GSK3beta within the mitochondria and found that this enhanced the apoptosis signaling activated by the PD-mimetic NADH:ubiquinone oxidoreductase (complex I) inhibitors 1-methyl-4-phenylpyridinium ion (MPP+) and rotenone. Additionally, expression of GSK3beta in the mitochondria itself caused a significant decrease in complex I activity and ATP production. Increased mitochondrial a GSK3beta activity also increased reactive oxygen species production and perturbed the mitochondrial morphology. Conversely, chemical inhibitors of GSK3beta inhibited MPP+- and rotenone-induced apoptosis, and attenuated the mitochondrial GSK3beta-mediated impairment in complex I. These results indicate that unregulated mitochondrial GSK3beta activity can mimic some of the mitochondrial insufficiencies found in PD pathology.

journal_name

Neurotox Res

journal_title

Neurotoxicity research

authors

King TD,Clodfelder-Miller B,Barksdale KA,Bijur GN

doi

10.1007/BF03033861

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

367-82

issue

4

eissn

1029-8428

issn

1476-3524

journal_volume

14

pub_type

杂志文章
  • Intracerebral Injection of Metal-Binding Domain of Aβ Comprising the Isomerized Asp7 Increases the Amyloid Burden in Transgenic Mice.

    abstract::Intracerebral or intraperitoneal injections of brain extracts from the Alzheimer's disease patients result in the acceleration of cerebral β-amyloidosis in transgenic mice. Earlier, we have found that intravenous injections of synthetic full-length amyloid-β (Aβ) comprising the isomerized Asp7 trigger cerebral β-amylo...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-016-9603-y

    authors: Kulikova AA,Cheglakov IB,Kukharsky MS,Ovchinnikov RK,Kozin SA,Makarov AA

    更新日期:2016-05-01 00:00:00

  • Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats.

    abstract::Inflammation can cause memory impairment. In the present study, the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide (LPS)-challenged rats was evaluated. The animals were grouped and treated: (1) control which received vehicle instead of LPS and...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-00144-5

    authors: Hakimi Z,Salmani H,Marefati N,Arab Z,Gholamnezhad Z,Beheshti F,Shafei MN,Hosseini M

    更新日期:2020-04-01 00:00:00

  • Glutathione transferase-M2-2 secreted from glioblastoma cell protects SH-SY5Y cells from aminochrome neurotoxicity.

    abstract::U373MG cells are able to take up aminochrome that induces glutathione transferase M2-2 (GSTM2) expression in a concentration-dependent manner where 100 µM aminochrome increases GSTM2 expression by 2.1-fold (P < 0.001) at 3 h. The uptake of (3)H-aminochrome into U373MG cells was significantly reduced in the presence of...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-014-9500-1

    authors: Cuevas C,Huenchuguala S,Muñoz P,Villa M,Paris I,Mannervik B,Segura-Aguilar J

    更新日期:2015-04-01 00:00:00

  • Small-molecule mediated neuroprotection in an in situ model of tauopathy.

    abstract::Small-molecule inhibitors of neurofibrillary lesion formation may have utility for treatment of Alzheimer's disease and certain forms of frontotemporal lobar degeneration. These lesions are composed largely of tau protein, which aggregates to form intracellular fibrils in affected neurons. Previously it was shown that...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-009-9028-y

    authors: Honson NS,Jensen JR,Abraha A,Hall GF,Kuret J

    更新日期:2009-04-01 00:00:00

  • Protective Effect of Hemin Against Experimental Chronic Fatigue Syndrome in Mice: Possible Role of Neurotransmitters.

    abstract::Chronic fatigue syndrome (CFS) is a disorder characterized by persistent and relapsing fatigue along with long-lasting and debilitating fatigue, myalgia, cognitive impairment, and many other common symptoms. The present study was conducted to explore the protective effect of hemin on CFS in experimental mice. Male alb...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-020-00231-y

    authors: Thakur V,Jamwal S,Kumar M,Rahi V,Kumar P

    更新日期:2020-08-01 00:00:00

  • Mechanism Underlying Organophosphate Paraoxon-Induced Kinetic Tremor.

    abstract::Organophosphates (OPs) inhibit cholinesterase and hyperactivate the acetylcholinergic nervous system in the brain, causing motor disorders (e.g., tremor and seizures). Here, we performed behavioral and immunohistochemical studies in mice and rats to investigate the tremorgenic mechanism of paraoxon, an active metaboli...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-0007-7

    authors: Iha HA,Kunisawa N,Shimizu S,Onishi M,Nomura Y,Matsubara N,Iwai C,Ogawa M,Hashimura M,Sato K,Kato M,Ohno Y

    更新日期:2019-04-01 00:00:00

  • Tanshinone I Induces Mitochondrial Protection by a Mechanism Involving the Nrf2/GSH Axis in the Human Neuroblastoma SH-SY5Y Cells Exposed to Methylglyoxal.

    abstract::Methylglyoxal (MG) is a dicarbonyl molecule exhibiting high reactivity and is a major responsible for glycation in human cells. Accumulation of MG is seen in certain diseases, including metabolic disturbances and neurodegeneration. Among other effects, MG promotes mitochondrial dysfunction, leading to bioenergetic dec...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-00091-1

    authors: Fürstenau CR,de Souza ICC,de Oliveira MR

    更新日期:2019-10-01 00:00:00

  • Baicalin Attenuates Ketamine-Induced Neurotoxicity in the Developing Rats: Involvement of PI3K/Akt and CREB/BDNF/Bcl-2 Pathways.

    abstract::Ketamine is widely used as an anesthetic in pediatric clinical practice. However, numerous studies have reported that exposure to ketamine during the developmental period induces neurotoxicity. Here we investigate the neuroprotective effects of baicalin, a natural flavonoid compound, against ketamine-induced apoptotic...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-016-9611-y

    authors: Zuo D,Lin L,Liu Y,Wang C,Xu J,Sun F,Li L,Li Z,Wu Y

    更新日期:2016-08-01 00:00:00

  • The novel free radical scavenger, edaravone, increases neural stem cell number around the area of damage following rat traumatic brain injury.

    abstract::Edaravone is a novel free radical scavenger that is clinically employed in patients with acute cerebral infarction, but has not previously been used to treat traumatic brain injury (TBI). In this study, we investigated the effect of edaravone administration on rat TBI. In particular, we used immunohistochemistry to mo...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-009-9081-6

    authors: Itoh T,Satou T,Nishida S,Tsubaki M,Hashimoto S,Ito H

    更新日期:2009-11-01 00:00:00

  • Early-Life Social Isolation-Induced Depressive-Like Behavior in Rats Results in Microglial Activation and Neuronal Histone Methylation that Are Mitigated by Minocycline.

    abstract::Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microgl...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-016-9696-3

    authors: Wang HT,Huang FL,Hu ZL,Zhang WJ,Qiao XQ,Huang YQ,Dai RP,Li F,Li CQ

    更新日期:2017-05-01 00:00:00

  • Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress.

    abstract::The sigma1 receptor (σ1R) is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it modulates Ca2+ exchange between the ER and mitochondria by interacting with inositol-1,4,5 trisphosphate receptors (IP3Rs). The σ1R is highly expressed in the central nervous syste...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-017-9838-2

    authors: Goguadze N,Zhuravliova E,Morin D,Mikeladze D,Maurice T

    更新日期:2019-01-01 00:00:00

  • Glycogen synthase kinase 3β and its phosphorylated form (Y216) in the paraquat-induced model of parkinsonism.

    abstract::Parkinson's disease is a slowly progressing disease, due to a lesion of dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in the striatum. It is now accepted that several environmental agents including the herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now nothing ...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-010-9153-7

    authors: Songin M,Strosznajder JB,Fitał M,Kuter K,Kolasiewicz W,Nowak P,Ossowska K

    更新日期:2011-01-01 00:00:00

  • Nanocapsules with Polyelectrolyte Shell as a Platform for 1,25-dihydroxyvitamin D3 Neuroprotection: Study in Organotypic Hippocampal Slices.

    abstract::Calcitriol (1,25-dihydroxyvitamin D3), an active metabolite of vitamin D3, besides the role in calcium and phosphorus metabolism, plays a role in maintaining the functions of the brain. Active forms of vitamin D3 stimulate neurotrophic factors' expression, regulate brain immune processes, and prevent neuronal damage. ...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-016-9652-2

    authors: Ślusarczyk J,Piotrowski M,Szczepanowicz K,Regulska M,Leśkiewicz M,Warszyński P,Budziszewska B,Lasoń W,Basta-Kaim A

    更新日期:2016-11-01 00:00:00

  • A neurodevelopmental model of schizophrenia: neonatal disconnection of the hippocampus.

    abstract::In the context of our current knowledge about schizophrenia, heuristic models of psychiatric disorders may be used to test the plausibility of theories developed on the basis of new emerging biological findings, explore mechanisms of schizophrenia-like phenomena, and develop potential new treatments. In a series of st...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1080/1029842021000022089

    authors: Lipska BK,Weinberger DR

    更新日期:2002-08-01 00:00:00

  • OSU-6162, a Sigma1R Ligand in Low Doses, Can Further Increase the Effects of Cocaine Self-Administration on Accumbal D2R Heteroreceptor Complexes.

    abstract::Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer (-) OSU-6162 (OSU-6162) with a nanomolar affinity for the Sigma1R can acutely modulate in low doses the effects of cocaine self-administration. In...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-00134-7

    authors: Borroto-Escuela DO,Romero-Fernandez W,Wydra K,Zhou Z,Suder A,Filip M,Fuxe K

    更新日期:2020-02-01 00:00:00

  • Breakdown of the Paracellular Tight and Adherens Junctions in the Gut and Blood Brain Barrier and Damage to the Vascular Barrier in Patients with Deficit Schizophrenia.

    abstract::Deficit schizophrenia is characterized by leaky intestinal tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular, and vascular barriers in the gut and blood-brain barriers. We measured IgA responses to occludin, cla...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-00054-6

    authors: Maes M,Sirivichayakul S,Kanchanatawan B,Vodjani A

    更新日期:2019-08-01 00:00:00

  • Chronic pretreatment with acetyl-L-carnitine and ±DL-α-lipoic acid protects against acute glutamate-induced neurotoxicity in rat brain by altering mitochondrial function.

    abstract::Cellular oxidative stress and energy failure were shown to be involved in Glutamate (L-Glu) neurotoxicity, whereas, acetyl-L-carnitine (ALCAR) and ±DL-α-lipoic acid (LA) are known to be key players in the mitochondrial energy production. To evaluate the effects of the above antioxidants, adult rats were pretreated wit...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-010-9165-3

    authors: Nagesh Babu G,Kumar A,Singh RL

    更新日期:2011-02-01 00:00:00

  • The neuroprotectant properties of glutamate antagonists and antiglutamatergic drugs.

    abstract::In the slowly progressive neurodegenerative disorders like Parkinson's disease and Alzheimer's disease very different neuronal populations undergo degenerative processes, although the cascades of cellular events leading to death are supposed to be similar. We suggest that the complex pattern of degeneration in Parkins...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/BF03033793

    authors: Pedersen V,Schmidt WJ

    更新日期:2000-01-01 00:00:00

  • Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization.

    abstract:BACKGROUND:Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin neutralization is classically attributed to the Fab and F(ab')2 fragments of antibodies. Herein, we generated Fab and F(ab')2 fragments of thre...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-00124-9

    authors: Ghotloo S,Amiri MM,Khoshnoodi J,Abbasi E,Jeddi-Tehrani M,Golsaz-Shirazi F,Shokri F

    更新日期:2020-03-01 00:00:00

  • 1MeTIQ provides protection against Aβ-induced reduction of surface expression of synaptic proteins and inhibits H₂O₂-induced oxidative stress in primary hippocampal neurons.

    abstract::Alzheimer's disease (AD) is associated with increased brain levels of β-amyloid (Aβ) peptides, which readily self-aggregate into fibrils and oligomers that have particularly deleterious properties toward synapses of excitatory glutamatergic neurons. Here, we examined the neuroprotective effects of 1-methyl-1,2,3,4,-te...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-013-9440-1

    authors: Kuszczyk MA,Sadowski MJ,Antkiewicz-Michaluk L,Lazarewicz JW

    更新日期:2014-05-01 00:00:00

  • Effect of chronic and subchronic organic solvents exposure on balance control of workers in plant manufacturing adhesive materials.

    abstract::High-level occupational exposure to volatile organic solvents may elicit neurotoxic effects, especially on central and peripheral structures involved in balance ability. Studies on balance control in relation with exposure levels close to the threshold limit values are scarce. This study aimed to assess the neurotoxic...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-009-9018-0

    authors: Herpin G,Gargouri I,Gauchard GC,Nisse C,Khadhraoui M,Elleuch B,Zmirou-Navier D,Perrin PP

    更新日期:2009-02-01 00:00:00

  • Dopamine receptor supersensitivity: development, mechanisms, presentation, and clinical applicability.

    abstract::The process of receptor supersensitivity (RSS) has a long history and is an epiphenomenon of neuronal denervation. Dopamine (DA) RSS (DARSS) similarly occurs after DA denervation, and this process is invoked in neuropsychiatric and neurodegenerative disorders. From studies largely over the past 25 years, much has been...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章,评审

    doi:10.1007/BF03033804

    authors: Kostrzewa RM,Kostrzewa JP,Brown RW,Nowak P,Brus R

    更新日期:2008-10-01 00:00:00

  • NMDA Receptors and Oxidative Stress Induced by the Major Metabolites Accumulating in HMG Lyase Deficiency Mediate Hypophosphorylation of Cytoskeletal Proteins in Brain From Adolescent Rats: Potential Mechanisms Contributing to the Neuropathology of This D

    abstract::Neurological symptoms and cerebral abnormalities are commonly observed in patients with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG lyase) deficiency, which is biochemically characterized by predominant tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), 3-methylglutaric (MGA), and 3-methylglutaconic (MGT) acids. S...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-015-9542-z

    authors: Fernandes CG,Pierozan P,Soares GM,Ferreira F,Zanatta Â,Amaral AU,Borges CG,Wajner M,Pessoa-Pureur R

    更新日期:2015-10-01 00:00:00

  • Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. a review.

    abstract::Cellular mechanisms involved in neurodegeneration and neuroprotection are continuing to be explored, and this paper focuses on some novel discoveries that give further insight into these processes. Oligodendrocytes and activated astroglia are likely generators of the pro-inflammatory cytokines, such as the tumor necro...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章,评审

    doi:10.1007/BF03033166

    authors: Kostrzewa RM,Segura-Aguilar J

    更新日期:2003-01-01 00:00:00

  • PACAP protects against inflammatory-mediated toxicity in dopaminergic SH-SY5Y cells: implication for Parkinson's disease.

    abstract::There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson's disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown ...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-014-9468-x

    authors: Brown D,Tamas A,Reglodi D,Tizabi Y

    更新日期:2014-10-01 00:00:00

  • Effects of Curcumin on Microglial Cells.

    abstract::Microglia are innate immune system cells which reside in the central nervous system (CNS). Resting microglia regulate the homeostasis of the CNS via phagocytic activity to clear pathogens and cell debris. Sometimes, however, to protect neurons and fight invading pathogens, resting microglia transform to an activated-f...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章,评审

    doi:10.1007/s12640-019-00030-0

    authors: Ghasemi F,Bagheri H,Barreto GE,Read MI,Sahebkar A

    更新日期:2019-07-01 00:00:00

  • Selenium Enhances the Apoptotic Efficacy of Docetaxel Through Activation of TRPM2 Channel in DBTRG Glioblastoma Cells.

    abstract::The rate of mitosis of cancer cells is significantly higher than normal primary cells with increased metabolic needs, which in turn enhances the generation of reactive oxygen species (ROS) production. Higher ROS production is known to increase cancer cell dependence on ROS scavenging systems to counteract the increase...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/s12640-019-0009-5

    authors: Ertilav K,Nazıroğlu M,Ataizi ZS,Braidy N

    更新日期:2019-05-01 00:00:00

  • Axonal degeneration and progressive neurologic disability in multiple sclerosis.

    abstract::Accumulating data support axonal degeneration as the major determinant of irreversible neurological disability in patients with multiple sclerosis (MS). The extent of axonal injury correlates with the degree of inflammation in active MS lesions and occurs at early stages of disease, indicating that inflammatory demyel...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/BF03033380

    authors: Bjartmar C,Trapp BD

    更新日期:2003-01-01 00:00:00

  • Subchronic administration of haloperidol influences the functional deficits of postnatal iron administration in mice.

    abstract::C57/BL6 mice were administered either 7.5 mg Fe (II)/ kg or vehicle (saline) postnatally on Days 10-12 after birth. From 64 days of age onwards for 24 days, groups of mice were administered either haloperidol (0.25 or 1 or 2 mg/kg, s.c.) or vehicle (Tween-80). Twenty-four hours after the final injection of either neur...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1007/BF03033321

    authors: Fredriksson A,Archer T

    更新日期:2006-06-01 00:00:00

  • Involvement of Maillard reactions in Alzheimer disease.

    abstract::Maillard reactions have been explored by food chemists for many years. It is only recently that the advanced glycation end products (AGEs), the end products of the Maillard reaction, have been detected in a wide variety of diseases such as diabetes, atherosclerosis, cataractogenesis, Parkinson disease and Alzheimer di...

    journal_title:Neurotoxicity research

    pub_type: 杂志文章

    doi:10.1080/1029840290007321

    authors: Reddy VP,Obrenovich ME,Atwood CS,Perry G,Smith MA

    更新日期:2002-05-01 00:00:00