schliessen

Filtern

 

Bibliotheken

Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA) neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or... Full description

Journal Title: PloS one 2012, Vol.7(4), p.e35645
Main Author: Sun, Yaping
Other Authors: Dong, Zhiqiang , Khodabakhsh, Hadie , Chatterjee, Sandip , Guo, Su
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 1932-6203 ; DOI: 10.1371/journal.pone.0035645
Link: http://search.proquest.com/docview/1011539317/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1011539317
title: Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.
format: Article
creator:
  • Sun, Yaping
  • Dong, Zhiqiang
  • Khodabakhsh, Hadie
  • Chatterjee, Sandip
  • Guo, Su
subjects:
  • Animals–Pharmacology
  • Antioxidants–Chemistry
  • Cardenolides–Pharmacology
  • Cardiac Glycosides–Chemistry
  • Cell Survival–Pharmacology
  • Dopaminergic Neurons–Drug Effects
  • Embryo, Nonmammalian–Cytology
  • Humans–Drug Effects
  • Oxidative Stress–Metabolism
  • Sodium-Potassium-Exchanging Atpase–Drug Effects
  • Tumor Suppressor Protein P53–Metabolism
  • Zebrafish–Metabolism
  • Zebrafish–Antagonists & Inhibitors
  • Zebrafish–Genetics
  • Zebrafish–Metabolism
  • Zebrafish–Growth & Development
  • Antioxidants
  • Cardenolides
  • Cardiac Glycosides
  • Tumor Suppressor Protein P53
  • Neriifolin
  • Sodium-Potassium-Exchanging Atpase
ispartof: PloS one, 2012, Vol.7(4), p.e35645
description: Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA) neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na.sup.+ /K.sup.+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na.sup.+ /K.sup.+ ATPase [alpha]3 subunit (ATP1A3). Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 1932-6203 ; DOI: 10.1371/journal.pone.0035645
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


@attributes
ID983512226
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1011539317
sourceidproquest
recordidTN_proquest1011539317
sourcesystemOther
pqid1011539317
galeid477041459
display
typearticle
titleZebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.
creatorSun, Yaping ; Dong, Zhiqiang ; Khodabakhsh, Hadie ; Chatterjee, Sandip ; Guo, Su
contributorSun, Yaping (correspondence author) ; Sun, Yaping (record owner)
ispartofPloS one, 2012, Vol.7(4), p.e35645
identifier
subjectAnimals–Pharmacology ; Antioxidants–Chemistry ; Cardenolides–Pharmacology ; Cardiac Glycosides–Chemistry ; Cell Survival–Pharmacology ; Dopaminergic Neurons–Drug Effects ; Embryo, Nonmammalian–Cytology ; Humans–Drug Effects ; Oxidative Stress–Metabolism ; Sodium-Potassium-Exchanging Atpase–Drug Effects ; Tumor Suppressor Protein P53–Metabolism ; Zebrafish–Metabolism ; Zebrafish–Antagonists & Inhibitors ; Zebrafish–Genetics ; Zebrafish–Metabolism ; Zebrafish–Growth & Development ; Antioxidants ; Cardenolides ; Cardiac Glycosides ; Tumor Suppressor Protein P53 ; Neriifolin ; Sodium-Potassium-Exchanging Atpase
languageeng
source
descriptionParkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA) neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na.sup.+ /K.sup.+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na.sup.+ /K.sup.+ ATPase [alpha]3 subunit (ATP1A3). Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.
version9
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1011539317/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Sun, Yaping
1Dong, Zhiqiang
2Khodabakhsh, Hadie
3Chatterjee, Sandip
4Guo, Su
titleZebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.
subject
0Animals–Pharmacology
1Antioxidants–Chemistry
2Cardenolides–Pharmacology
3Cardiac Glycosides–Chemistry
4Cell Survival–Pharmacology
5Dopaminergic Neurons–Drug Effects
6Embryo, Nonmammalian–Cytology
7Humans–Drug Effects
8Oxidative Stress–Metabolism
9Sodium-Potassium-Exchanging Atpase–Drug Effects
10Tumor Suppressor Protein P53–Metabolism
11Zebrafish–Metabolism
12Zebrafish–Antagonists & Inhibitors
13Zebrafish–Genetics
14Zebrafish–Growth & Development
15Antioxidants
16Cardenolides
17Cardiac Glycosides
18Tumor Suppressor Protein P53
19Neriifolin
20Sodium-Potassium-Exchanging Atpase
general
0English
11932-6203
210.1371/journal.pone.0035645
3MEDLINE (ProQuest)
4ProQuest Biological Science Collection
5ProQuest Natural Science Collection
6ProQuest SciTech Collection
7Biological Science Database
8Natural Science Collection
9SciTech Premium Collection
10Health Research Premium Collection
11Health Research Premium Collection (Alumni edition)
sourceidproquest
recordidproquest1011539317
issn
019326203
11932-6203
rsrctypearticle
creationdate2012
addtitlePloS one
searchscope
01007527
11007944
210000004
310000038
410000050
510000120
610000159
710000238
810000253
910000260
1010000270
1110000271
1210000302
13proquest
scope
01007527
11007944
210000004
310000038
410000050
510000120
610000159
710000238
810000253
910000260
1010000270
1110000271
1210000302
13proquest
lsr43
01007527false
11007944false
210000004false
310000038false
410000050false
510000120false
610000159false
710000238false
810000253false
910000260false
1010000270false
1110000271false
1210000302false
contributorSun, Yaping
startdate20120101
enddate20120101
citationpf e35645 pt e35645 vol 7 issue 4
lsr30VSR-Enriched:[galeid, description, pqid]
sort
titleZebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.
authorSun, Yaping ; Dong, Zhiqiang ; Khodabakhsh, Hadie ; Chatterjee, Sandip ; Guo, Su
creationdate20120101
lso0120120101
facets
frbrgroupid8029420678460702881
frbrtype5
newrecords20181218
languageeng
creationdate2012
topic
0Animals–Pharmacology
1Antioxidants–Chemistry
2Cardenolides–Pharmacology
3Cardiac Glycosides–Chemistry
4Cell Survival–Pharmacology
5Dopaminergic Neurons–Drug Effects
6Embryo, Nonmammalian–Cytology
7Humans–Drug Effects
8Oxidative Stress–Metabolism
9Sodium-Potassium-Exchanging Atpase–Drug Effects
10Tumor Suppressor Protein P53–Metabolism
11Zebrafish–Metabolism
12Zebrafish–Antagonists & Inhibitors
13Zebrafish–Genetics
14Zebrafish–Growth & Development
15Antioxidants
16Cardenolides
17Cardiac Glycosides
18Tumor Suppressor Protein P53
19Neriifolin
20Sodium-Potassium-Exchanging Atpase
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
prefilterarticles
rsrctypearticles
creatorcontrib
0Sun, Yaping
1Dong, Zhiqiang
2Khodabakhsh, Hadie
3Chatterjee, Sandip
4Guo, Su
jtitlePloS one
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Sun
1Dong
2Khodabakhsh
3Chatterjee
4Guo
aufirst
0Yaping
1Zhiqiang
2Hadie
3Sandip
4Su
au
0Sun, Yaping
1Dong, Zhiqiang
2Khodabakhsh, Hadie
3Chatterjee, Sandip
4Guo, Su
addauSun, Yaping
atitleZebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.
jtitlePloS one
risdate20120101
volume7
issue4
spagee35645
epagee35645
pagese35645
eissn1932-6203
formatjournal
genrearticle
ristypeJOUR
doi10.1371/journal.pone.0035645
urlhttp://search.proquest.com/docview/1011539317/
date2012-01-01