LIVIVO - Search results -

Search results

Result 1 - 10 of total 11

Search options

Article ; Online: Anticardiolipin (aCL) in sera from periodontitis subjects activate Toll-like receptor 4 (TLR4).

Schenkein, Harvey A / Thomas, Ravindar R

PloS one

2018 Volume 13, Issue 9, Page(s) e0203494

Abstract: Anticardiolipin antibodies (aCL) have been reported to be present in 15-20% of sera from subjects with periodontitis at concentrations exceeding those found in 95% of the healthy adult population. These antibodies, albeit at concentrations exceeding ... ...

Abstract	Anticardiolipin antibodies (aCL) have been reported to be present in 15-20% of sera from subjects with periodontitis at concentrations exceeding those found in 95% of the healthy adult population. These antibodies, albeit at concentrations exceeding those generally found in periodontitis subjects, are typically present in patients with the antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. aCL from APS patients are proinflammatory and can activate trophoblasts, macrophages, and platelets via cell-surface interactions with their target antigen beta-2-glycoprotein-I (β2GPI). β2GPI is an anionic phospholipid-binding serum protein that can associate with toll-like receptors (TLR's) on the cell-surface, leading to cell activation following interaction with autoimmune aCL. We examined an expanded series of 629 sera from clinically characterized subjects for aCL content, and observed that 14-19% of these sera contained elevated (>95th %-tile) levels of aCL. We purified IgG from 16 subjects with elevated or normal levels of aCL and examined their ability to activate TLR2- or TLR4-transfected human embryonic kidney (HEK) cells, and observed that IgG from periodontitis patients with elevated aCL activated HEK-TLR4 cells, but not HEK-TLR2 cells. Prior removal of aCL by immunoabsorption significantly reduced the ability of IgG preparations from these sera to activate TLR4. Further experiments using a human first trimester trophoblastic cell line (HTR8 sv/neo) revealed that aCL from periodontitis patients stimulated IL-8 production, which was profoundly decreased if aCL was removed by immunoabsorption or if HTR8 sv/neo were pretreated with blocking anti-TLR4 antibodies. Thus, it appears that aCL from periodontitis patients can be proinflammatory, activating cells via TLR4. Since these antibodies are likely produced via molecular mimicry due to similarities between oral bacterial antigens and β2GPI, the data indicate that circulating serum aCL may induce or influence inflammatory responses at sites distant from the oral cavity.
MeSH term(s)	Adult ; Antibodies, Anticardiolipin/blood ; Antiphospholipid Syndrome/blood ; Antiphospholipid Syndrome/immunology ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Periodontitis/blood ; Periodontitis/immunology ; Toll-Like Receptor 4/immunology ; Young Adult ; beta 2-Glycoprotein I/blood ; beta 2-Glycoprotein I/immunology
Chemical Substances	Antibodies, Anticardiolipin ; Immunoglobulin G ; TLR4 protein, human ; Toll-Like Receptor 4 ; beta 2-Glycoprotein I
Language	English
Publishing date	2018-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0203494
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Epigenetic Modifications of the PGC-1α Promoter during Exercise Induced Expression in Mice.

Lochmann, Timothy L / Thomas, Ravindar R / Bennett, James P / Taylor, Shirley M

PloS one

2015 Volume 10, Issue 6, Page(s) e0129647

Abstract: The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One ...

Abstract	The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7 kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not yet known what molecular changes occur to facilitate PGC-1α promoter B activation following exercise. We sought to determine whether epigenetic modifications were involved in this exercise response in mouse skeletal muscle. We found that DNA hydroxymethylation correlated to increased basal mRNA levels from PGC-1α promoter A, but that DNA methylation appeared to play no role in the exercise-induced activation of PGC-1α promoter B. The level of the activating histone mark H3K4me3 increased with exercise 2-4 fold across PGC-1α promoter B, but remained unaltered past the canonical PGC-1α transcriptional start site. Together, these data show that epigenetic modifications partially explain exercise-induced changes in the skeletal muscle mRNA levels of PGC-1α isoforms.
MeSH term(s)	Alternative Splicing ; Animals ; DNA Methylation ; Epigenesis, Genetic ; Exons ; Female ; Gene Expression Regulation ; Histones/metabolism ; Mice ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Physical Conditioning, Animal ; Promoter Regions, Genetic ; RNA, Messenger/genetics ; Transcription Factors/genetics ; Transcription Initiation Site
Chemical Substances	Histones ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Ppargc1a protein, mouse ; RNA, Messenger ; Transcription Factors
Language	English
Publishing date	2015-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0129647
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Epigenetic Modifications of the PGC-1α Promoter during Exercise Induced Expression in Mice.

Timothy L Lochmann / Ravindar R Thomas / James P Bennett / Shirley M Taylor

PLoS ONE, Vol 10, Iss 6, p e

2015 Volume 0129647

Abstract	The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7 kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not yet known what molecular changes occur to facilitate PGC-1α promoter B activation following exercise. We sought to determine whether epigenetic modifications were involved in this exercise response in mouse skeletal muscle. We found that DNA hydroxymethylation correlated to increased basal mRNA levels from PGC-1α promoter A, but that DNA methylation appeared to play no role in the exercise-induced activation of PGC-1α promoter B. The level of the activating histone mark H3K4me3 increased with exercise 2-4 fold across PGC-1α promoter B, but remained unaltered past the canonical PGC-1α transcriptional start site. Together, these data show that epigenetic modifications partially explain exercise-induced changes in the skeletal muscle mRNA levels of PGC-1α isoforms.
Keywords	Medicine ; R ; Science ; Q
Subject code	572 ; 570
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Impaired complex-I mitochondrial biogenesis in Parkinson disease frontal cortex.

Thomas, Ravindar R / Keeney, Paula M / Bennett, James P

Journal of Parkinson's disease

2012 Volume 2, Issue 1, Page(s) 67–76

Abstract: Parkinson's disease (PD) can include a progressive frontal lobe α-synucleinopathy with disability from cognitive decline and cortico-limbic dysregulation that may arise from bioenergetic impairments. We examined in PD frontal cortex regulation of ... ...

Abstract	Parkinson's disease (PD) can include a progressive frontal lobe α-synucleinopathy with disability from cognitive decline and cortico-limbic dysregulation that may arise from bioenergetic impairments. We examined in PD frontal cortex regulation of mitochondrial biogenesis (mitobiogenesis) and its effects on Complex-I. We quantified expression of 33 nuclear genome (nDNA)-encoded and 7 mitochondrial genome (mtDNA)-encoded Complex-I genes, 6 Complex-I assembly factors and multiple mitobiogenesis genes. We related these findings to levels of Complex-I proteins and NADH-driven electron flow in mitochondria from these same specimens reported in earlier studies. We found widespread, decreased expression of nDNA Complex-I genes that correlated in some cases with mitochondrial Complex-I protein levels, and of ACAD9, a Complex-I assembly factor. mtDNA-transcribed Complex-I genes showed ~ constant expression within each PD sample but variable expression across PD samples that correlated with NRF1. Relationships among PGC-1α and its downstream targets NRF1 and TFAM were very similar in PD and CTL and were related to mitochondrial NADH-driven electron flow. MicroRNA arrays revealed multiple miRNA's regulated >2-fold predicted to interact with PGC-1α or its upstream regulators. Exposure of cultured human neurons to NO, rotenone and TNF-alpha partially reproduced mitobiogenesis down-regulation. In PD frontal cortex mitobiogenesis signaling relationships are maintained but down-regulated, correlate with impaired mitochondrial NADH-driven electron flow and may arise from combinations of nitrosative/oxidative stresses, inflammatory cytokines, altered levels of mitobiogenesis gene-interacting microRNA's, or other unknown mechanisms. Stimulation of mitobiogenesis in PD may inhibit rostral disease progression and appearance of secondary symptoms referable to frontal cortex.
MeSH term(s)	Acyl-CoA Dehydrogenases/genetics ; Acyl-CoA Dehydrogenases/metabolism ; Adolescent ; Cell Line ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Dopaminergic Neurons/ultrastructure ; Electron Transport Complex I/genetics ; Electron Transport Complex I/metabolism ; Female ; Frontal Lobe/pathology ; Frontal Lobe/physiopathology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Humans ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Microarray Analysis ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Mitochondrial Turnover/physiology ; Neural Stem Cells ; Nuclear Respiratory Factor 1/genetics ; Nuclear Respiratory Factor 1/metabolism ; Parkinson Disease/pathology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rotenone/pharmacology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
Chemical Substances	DNA-Binding Proteins ; MicroRNAs ; Mitochondrial Proteins ; NRF1 protein, human ; Nuclear Respiratory Factor 1 ; PPARGC1A protein, human ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; TFAM protein, human ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Rotenone (03L9OT429T) ; Acyl-CoA Dehydrogenases (EC 1.3.-) ; ACAD9 protein, human (EC 1.3.99.-) ; Electron Transport Complex I (EC 1.6.5.3)
Language	English
Publishing date	2012
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-2012-11074
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6964: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: RNA-seq analyses reveal that cervical spinal cords and anterior motor neurons from amyotrophic lateral sclerosis subjects show reduced expression of mitochondrial DNA-encoded respiratory genes, and rhTFAM may correct this respiratory deficiency.

Ladd, Amy C / Brohawn, David G / Thomas, Ravindar R / Keeney, Paula M / Berr, Stuart S / Khan, Shaharyar M / Portell, Francisco R / Shakenov, Meiram Zh / Antkowiak, Patrick F / Kundu, Bijoy / Tustison, Nicholas / Bennett, James P

Brain research

2017 Volume 1667, Page(s) 74–83

Abstract: Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative disease of adults that produces weakness and atrophy due to dysfunction and death of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze expression of all ... ...

Abstract	Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative disease of adults that produces weakness and atrophy due to dysfunction and death of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3-dimensions clustered gene networks activated by rhTFAM, quantitated their interactions with other genes and determined their gene ontology (GO) families. RNA-seq and quantitative PCR (qPCR) analyses showed reduced mitochondrial gene expression in ALS hCSC and ALS motor neurons isolated by laser capture microdissection (LCM), and revealed that hNSC and CTL human cervical spinal cords were similar. Rats treated with i.v. rhTFAM showed a dose-response increase in brain respiration and an increase in spinal cord mitochondrial gene expression. Treatment of hNSC with rhTFAM increased expression of mtDNA-encoded respiratory genes and produced one major and several minor clusters of gene interactions. Gene ontology (GO) analysis of rhTFAM-stimulated gene clusters revealed enrichment in GO families involved in RNA and mRNA metabolism, suggesting mitochondrial-nuclear signaling. In postmortem ALS hCSC and LCM-isolated motor neurons we found reduced expression of mtDNA respiratory genes. In hNSC's rhTFAM increased mtDNA gene expression and stimulated mRNA metabolism by unclear mechanisms. rhTFAM may be useful in improving bioenergetic function in ALS.
MeSH term(s)	Amyotrophic Lateral Sclerosis/metabolism ; Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Cells, Cultured ; Cervical Cord/metabolism ; DNA, Mitochondrial ; DNA-Binding Proteins/administration & dosage ; DNA-Binding Proteins/metabolism ; Gene Expression ; Glucose/metabolism ; Humans ; Laser Capture Microdissection ; Male ; Mitochondrial Proteins/administration & dosage ; Mitochondrial Proteins/metabolism ; Motor Neurons/metabolism ; Neural Stem Cells/metabolism ; Rats, Sprague-Dawley ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/metabolism ; Sequence Analysis, RNA ; Transcription Factors/administration & dosage ; Transcription Factors/metabolism
Chemical Substances	DNA, Mitochondrial ; DNA-Binding Proteins ; Mitochondrial Proteins ; Recombinant Proteins ; Transcription Factors ; mitochondrial transcription factor A ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2017-05-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2017.05.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 161: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer's disease hippocampi.

Rice, Ann C / Keeney, Paula M / Algarzae, Norah K / Ladd, Amy C / Thomas, Ravindar R / Bennett, James P

Journal of Alzheimer's disease : JAD

2014 Volume 40, Issue 2, Page(s) 319–330

Abstract: Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial ... ...

Abstract	Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1α were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal Aβ1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment Aβ25-35, mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; DNA, Mitochondrial/genetics ; Diphtheria Toxin/pharmacology ; Female ; Gene Dosage/drug effects ; Gene Dosage/physiology ; Glial Fibrillary Acidic Protein/metabolism ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Laser Capture Microdissection ; Male ; Neural Stem Cells/drug effects ; Neuroglia/drug effects ; Neuroglia/metabolism ; Peptide Fragments/metabolism ; Peptide Fragments/pharmacology ; Pyramidal Cells/metabolism ; Pyramidal Cells/pathology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Statistics as Topic ; Transcriptome/genetics
Chemical Substances	Amyloid beta-Peptides ; DNA, Mitochondrial ; Diphtheria Toxin ; Glial Fibrillary Acidic Protein ; Peptide Fragments ; amyloid beta-protein (1-42) ; diphtheria toxin fragment A
Language	English
Publishing date	2014
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-131715
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6084: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Recombinant human mitochondrial transcription factor A stimulates mitochondrial biogenesis and ATP synthesis, improves motor function after MPTP, reduces oxidative stress and increases survival after endotoxin

Thomas, Ravindar R / Khan, Shaharyar M / Portell, Francisco R / Smigrodzki, Rafal M / Bennett, James P., Jr

Mitochondrion. 2011 Jan., v. 11, no. 1

2011

Abstract: Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive ... ...

Abstract	Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive manner. SH-SY5Y cells showed rhTFAM concentration-dependent reduction of methylpyridinium (MPP+)-induced oxidative stress and increases in lowered ATP levels and viability. Mice treated with weekly i.v. rhTFAM showed increased mitochondrial gene copy number, complex I protein levels and ATP production rates; oxidative damage to proteins was decreased ~50%. rhTFAM treatment improved motor recovery rate after treatment with MPTP and dose-dependently improved survival in the lipopolysaccharide model of endotoxin sepsis.
Keywords	sepsis (infection) ; transcription factors ; viability ; lipopolysaccharides ; humans ; long term effects ; biogenesis ; models ; adenosine triphosphate ; mice ; acute effects ; cultured cells ; fibroblasts ; endotoxins ; oxidative stress ; gene dosage
Language	English
Dates of publication	2011-01
Size	p. 108-118.
Publishing place	Elsevier B.V.
Document type	Article
Note	2019-12-04
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2010.08.004
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Article ; Online: Recombinant human mitochondrial transcription factor A stimulates mitochondrial biogenesis and ATP synthesis, improves motor function after MPTP, reduces oxidative stress and increases survival after endotoxin.

Thomas, Ravindar R / Khan, Shaharyar M / Portell, Francisco R / Smigrodzki, Rafal M / Bennett, James P

Mitochondrion

2010 Volume 11, Issue 1, Page(s) 108–118

Abstract	Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive manner. SH-SY5Y cells showed rhTFAM concentration-dependent reduction of methylpyridinium (MPP(+))-induced oxidative stress and increases in lowered ATP levels and viability. Mice treated with weekly i.v. rhTFAM showed increased mitochondrial gene copy number, complex I protein levels and ATP production rates; oxidative damage to proteins was decreased ~50%. rhTFAM treatment improved motor recovery rate after treatment with MPTP and dose-dependently improved survival in the lipopolysaccharide model of endotoxin sepsis.
MeSH term(s)	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/administration & dosage ; Adenosine Triphosphate/biosynthesis ; Animals ; Cell Line, Tumor ; Cell Respiration/drug effects ; Cell Survival ; DNA, Mitochondrial/drug effects ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; DNA-Binding Proteins/administration & dosage ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/pharmacology ; Endotoxemia/drug therapy ; Endotoxemia/mortality ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondrial Proteins/administration & dosage ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Mitochondrial Proteins/pharmacology ; Motor Activity/drug effects ; Motor Activity/physiology ; Neurons/drug effects ; Neurons/metabolism ; Neurons/physiology ; Oxidative Stress/drug effects ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Recombinant Proteins/pharmacology ; Transcription Factors/administration & dosage ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription Factors/pharmacology
Chemical Substances	DNA, Mitochondrial ; DNA-Binding Proteins ; Mitochondrial Proteins ; Recombinant Proteins ; Transcription Factors ; mitochondrial transcription factor A ; Adenosine Triphosphate (8L70Q75FXE) ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (9P21XSP91P)
Language	English
Publishing date	2010-08-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2010.08.004
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: RhTFAM treatment stimulates mitochondrial oxidative metabolism and improves memory in aged mice.

Thomas, Ravindar R / Khan, Shaharyar M / Smigrodzki, Rafal M / Onyango, Isaac G / Dennis, Jameel / Khan, Omer M / Portelli, Francisco R / Bennett, James P

Aging

2012 Volume 4, Issue 9, Page(s) 620–635

Abstract: Mitochondrial function declines with age in postmitotic tissues such as brain, heart and skeletal muscle. Despite weekly exercise, aged mice showed substantial losses of mtDNA gene copy numbers and reductions in mtDNA gene transcription and ... ...

Abstract	Mitochondrial function declines with age in postmitotic tissues such as brain, heart and skeletal muscle. Despite weekly exercise, aged mice showed substantial losses of mtDNA gene copy numbers and reductions in mtDNA gene transcription and mitobiogenesis signaling in brain and heart. We treated these mice with weekly intravenous injections of recombinant human mitochondrial transcription factor A (rhTFAM). RhTFAM treatment for one month increased mitochondrial respiration in brain, heart and muscle, POLMRT expression and mtDNA gene transcription in brain, and PGC-1 alpha mitobiogenesis signaling in heart. RhTFAM treatment reduced oxidative stress damage to brain proteins, improved memory in Morris water maze performance and increased brain protein levels of BDNF and synapsin. Microarray analysis showed co-expression of multiple Gene Ontology families in rhTFAM-treated aged brains compared to young brains. RhTFAM treatment reverses age-related memory impairments associated with loss of mitochondrial energy production in brain, increases levels of memory-related brain proteins and improves mitochondrial respiration in brain and peripheral tissues.
MeSH term(s)	Aging ; Animals ; Blotting, Western ; Cell Respiration/drug effects ; DNA, Mitochondrial/drug effects ; DNA-Binding Proteins/pharmacology ; Gene Expression/drug effects ; Humans ; Maze Learning/drug effects ; Memory/drug effects ; Mice ; Mitochondria/drug effects ; Mitochondrial Proteins/pharmacology ; Multiplex Polymerase Chain Reaction ; Oligonucleotide Array Sequence Analysis ; Oxidative Phosphorylation/drug effects ; Recombinant Proteins/pharmacology ; Transcription Factors/pharmacology
Chemical Substances	DNA, Mitochondrial ; DNA-Binding Proteins ; Mitochondrial Proteins ; Recombinant Proteins ; TFAM protein, human ; Transcription Factors
Language	English
Publishing date	2012-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.100488
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression.

Iyer, Shilpa / Thomas, Ravindar R / Portell, Francisco R / Dunham, Lisa D / Quigley, Caitlin K / Bennett, James P

Mitochondrion

2009 Volume 9, Issue 3, Page(s) 196–203

Abstract: We developed a scalable procedure to produce human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter ... ...

Abstract	We developed a scalable procedure to produce human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its "mitochondrial transduction domain" (MTD=PTD+MLS). Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment of cybrid cells carrying the G11778A LHON mutation. MTD-TFAM reversibly increased respiration and levels of respiratory proteins. In vivo treatment of mice with MTD-TFAM increased motor endurance and complex I-driven respiration in mitochondria from brain and skeletal muscle. MTD-TFAM increases mitochondrial bioenergetics and holds promise for treatment of mitochondrial diseases involving deficiencies of energy production.
MeSH term(s)	Adult ; Cell Line ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression ; Genes, Mitochondrial ; Humans ; Male ; Mitochondria/metabolism ; Mitochondrial Proteins/biosynthesis ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Protein Sorting Signals ; Protein Transport ; Respiration ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Mitochondrial Proteins ; Protein Sorting Signals ; Transcription Factors ; mitochondrial transcription factor A
Language	English
Publishing date	2009-02-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2009.01.012
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito