PMID- 31734880
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20240423
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 57
IP  - 3
DP  - 2020 Mar
TI  - Alterations of Transcription of Genes Coding Anti-oxidative and 
      Mitochondria-Related Proteins in Amyloid beta Toxicity: Relevance to Alzheimer's 
      Disease.
PG  - 1374-1388
LID - 10.1007/s12035-019-01819-y [doi]
AB  - A growing body of evidence indicates that pathological forms of amyloid beta (Abeta) 
      peptide contribute to neuronal degeneration and synaptic loss in Alzheimer's 
      disease (AD). In this study, we investigated the impact of exogenous Abeta(1-42) 
      oligomers (AbetaO) and endogenously liberated Abeta peptides on transcription of genes 
      for anti-oxidative and mitochondria-related proteins in cell lines (neuronal 
      SH-SY5Y and microglial BV2) and in brain cortex of transgenic AD (Tg-AD) mice, 
      respectively. Our results demonstrated significant AbetaO-evoked changes in 
      transcription of genes in SH-SY5Y cells, where AbetaO enhanced expression of Sod1, 
      Cat, mt-Nd1, Bcl2, and attenuated Sirt5, Sod2 and Sdha. In BV2 line, AbetaO 
      increased the level of mRNA for Sod2, Dnm1l, Bcl2, and decreased for Gpx4, Sirt1, 
      Sirt3, mt-Nd1, Sdha and Mfn2. Then, AbetaO enhanced free radicals level and impaired 
      mitochondrial membrane potential only in SH-SY5Y cells, but reduced viability of 
      both cell types. Inhibitor of poly(ADP-ribose)polymerase-1 and activator of 
      sirtuin-1 more efficiently enhanced viability of SH-SY5Y than BV2 affected by 
      AbetaO. Analysis of brain cortex of Tg-AD mice confirmed significant downregulation 
      of Sirt1, Mfn1 and mt-Nd1 and upregulation of Dnm1l. In human AD brain, changes 
      of microRNA pattern (miRNA-9, miRNA-34a, miRNA-146a and miRNA-155) seem to be 
      responsible for decrease in Sirt1 expression. Overall, our results demonstrated a 
      diverse response of neuronal and microglial cells to AbetaO toxicity. Alterations of 
      genes encoding Sirt1, Mfn1 and Drp1 in an experimental model of AD suggest that 
      modulation of mitochondria dynamics and Sirt1, including miRNA strategy, may be 
      crucial for improvement of AD therapy.
FAU - Cieslik, Magdalena
AU  - Cieslik M
AD  - Department of Cellular Signaling, Mossakowski Medical Research Centre Polish 
      Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland.
FAU - Czapski, Grzegorz A
AU  - Czapski GA
AD  - Department of Cellular Signaling, Mossakowski Medical Research Centre Polish 
      Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland.
FAU - Wojtowicz, Sylwia
AU  - Wojtowicz S
AD  - Department of Cellular Signaling, Mossakowski Medical Research Centre Polish 
      Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland.
FAU - Wieczorek, Iga
AU  - Wieczorek I
AD  - Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical 
      Research Centre Polish Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, 
      Poland.
FAU - Wencel, Przemyslaw L
AU  - Wencel PL
AD  - Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical 
      Research Centre Polish Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, 
      Poland.
FAU - Strosznajder, Robert P
AU  - Strosznajder RP
AD  - Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical 
      Research Centre Polish Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, 
      Poland.
FAU - Jaber, Vivian
AU  - Jaber V
AD  - LSU Neuroscience Center, Louisiana State University Health Sciences Center, New 
      Orleans, LA, 70112, USA.
FAU - Lukiw, Walter J
AU  - Lukiw WJ
AD  - LSU Neuroscience Center, Louisiana State University Health Sciences Center, New 
      Orleans, LA, 70112, USA.
AD  - Bollinger Professor of Alzheimer's disease, LSU Neuroscience Center and 
      Departments of Neurology and Ophthalmology, Louisiana State University Health 
      Sciences Center, New Orleans, LA, 70112, USA.
FAU - Strosznajder, Joanna B
AU  - Strosznajder JB
AUID- ORCID: 0000-0002-6213-1212
AD  - Department of Cellular Signaling, Mossakowski Medical Research Centre Polish 
      Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland. 
      jstrosznajder@imdik.pan.pl.
LA  - eng
GR  - NIA AG18031/NH/NIH HHS/United States
GR  - NIA AG038834/NH/NIH HHS/United States
GR  - NEI EY006311/NH/NIH HHS/United States
GR  - R01 AG038834/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20191116
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (MicroRNAs)
RN  - 0 (Mitochondrial Proteins)
SB  - IM
MH  - Alzheimer Disease/*metabolism/pathology
MH  - Amyloid beta-Peptides/metabolism/*toxicity
MH  - Animals
MH  - Humans
MH  - Mice
MH  - MicroRNAs/metabolism
MH  - Microglia/metabolism
MH  - Mitochondria/genetics/metabolism
MH  - Mitochondrial Proteins/metabolism/*toxicity
MH  - Neurons/metabolism
MH  - Oxidative Stress/*genetics
PMC - PMC7061023
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid beta
OT  - Gene expression
OT  - Microglial cells
OT  - Neuronal cells
OT  - miRNA-146a
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/11/18 06:00
MHDA- 2020/12/15 06:00
PMCR- 2019/11/16
CRDT- 2019/11/18 06:00
PHST- 2019/06/24 00:00 [received]
PHST- 2019/10/23 00:00 [accepted]
PHST- 2019/11/18 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2019/11/18 06:00 [entrez]
PHST- 2019/11/16 00:00 [pmc-release]
AID - 10.1007/s12035-019-01819-y [pii]
AID - 1819 [pii]
AID - 10.1007/s12035-019-01819-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2020 Mar;57(3):1374-1388. doi: 10.1007/s12035-019-01819-y. Epub 
      2019 Nov 16.