Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases
Identifieur interne : 000203 ( Main/Exploration ); précédent : 000202; suivant : 000204Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases
Auteurs : Moonhee Lee ; Edith G. Mcgeer ; Patrick L. McgeerSource :
- Journal of Neuroinflammation [ 1742-2094 ] ; 2016.
Abstract
Sodium thiosulfate (STS) is an industrial chemical which has also been approved for the treatment of certain rare medical conditions. These include cyanide poisoning and calciphylaxis in hemodialysis patients with end-stage kidney disease. Here, we investigated the anti-inflammatory activity of STS in our glial-mediated neuroinflammatory model.
Firstly, we measured glutathione (GSH) and hydrogen sulfide (H2S, SH−) levels in glial cells after treatment with sodium hydrosulfide (NaSH) or STS. We also measured released levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) from them. We used two cell viability assays, MTT and lactate dehydrogenase (LDH) release assays, to investigate glial-mediated neurotoxicity and anti-inflammatory effects of NaSH or STS. We also employed Western blot to examine activation of intracellular inflammatory pathways.
We found that STS increases H2S and GSH expression in human microglia and astrocytes. When human microglia and astrocytes are activated by lipopolysaccharide (LPS)/interferon-γ (IFNγ) or IFNγ, they release materials that are toxic to differentiated SH-SY5Y cells. When the glial cells were treated with NaSH or STS, there was a significant enhancement of neuroprotection. The effect was concentration-dependent and incubation time-dependent. Such treatment reduced the release of TNFα and IL-6 and also attenuated activation of P38 MAPK and NFκB proteins. The compounds tested were not harmful when applied directly to all the cell types.
Although NaSH was somewhat more powerful than STS in these in vitro assays, STS has already been approved as an orally available treatment. STS may therefore be a candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component.
The online version of this article (doi:10.1186/s12974-016-0488-8) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12974-016-0488-8
PubMed: 26856696
PubMed Central: 4746933
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000257
- to stream Pmc, to step Curation: 000257
- to stream Pmc, to step Checkpoint: 000062
- to stream Ncbi, to step Merge: 001E64
- to stream Ncbi, to step Curation: 001E64
- to stream Ncbi, to step Checkpoint: 001E64
- to stream Main, to step Merge: 000203
- to stream Main, to step Curation: 000203
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases</title><author><name sortKey="Lee, Moonhee" sort="Lee, Moonhee" uniqKey="Lee M" first="Moonhee" last="Lee">Moonhee Lee</name><affiliation><nlm:aff id="Aff1">Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada</nlm:aff><wicri:noCountry code="subfield">BC V6T 1Z3 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Mcgeer, Edith G" sort="Mcgeer, Edith G" uniqKey="Mcgeer E" first="Edith G." last="Mcgeer">Edith G. Mcgeer</name><affiliation><nlm:aff id="Aff1">Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada</nlm:aff><wicri:noCountry code="subfield">BC V6T 1Z3 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L." last="Mcgeer">Patrick L. Mcgeer</name><affiliation><nlm:aff id="Aff1">Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada</nlm:aff><wicri:noCountry code="subfield">BC V6T 1Z3 Canada</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26856696</idno><idno type="pmc">4746933</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746933</idno><idno type="RBID">PMC:4746933</idno><idno type="doi">10.1186/s12974-016-0488-8</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000257</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000257</idno><idno type="wicri:Area/Pmc/Curation">000257</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000257</idno><idno type="wicri:Area/Pmc/Checkpoint">000062</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000062</idno><idno type="wicri:Area/Ncbi/Merge">001E64</idno><idno type="wicri:Area/Ncbi/Curation">001E64</idno><idno type="wicri:Area/Ncbi/Checkpoint">001E64</idno><idno type="wicri:Area/Main/Merge">000203</idno><idno type="wicri:Area/Main/Curation">000203</idno><idno type="wicri:Area/Main/Exploration">000203</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases</title><author><name sortKey="Lee, Moonhee" sort="Lee, Moonhee" uniqKey="Lee M" first="Moonhee" last="Lee">Moonhee Lee</name><affiliation><nlm:aff id="Aff1">Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada</nlm:aff><wicri:noCountry code="subfield">BC V6T 1Z3 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Mcgeer, Edith G" sort="Mcgeer, Edith G" uniqKey="Mcgeer E" first="Edith G." last="Mcgeer">Edith G. Mcgeer</name><affiliation><nlm:aff id="Aff1">Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada</nlm:aff><wicri:noCountry code="subfield">BC V6T 1Z3 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L." last="Mcgeer">Patrick L. Mcgeer</name><affiliation><nlm:aff id="Aff1">Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada</nlm:aff><wicri:noCountry code="subfield">BC V6T 1Z3 Canada</wicri:noCountry></affiliation></author></analytic><series><title level="j">Journal of Neuroinflammation</title><idno type="eISSN">1742-2094</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Sodium thiosulfate (STS) is an industrial chemical which has also been approved for the treatment of certain rare medical conditions. These include cyanide poisoning and calciphylaxis in hemodialysis patients with end-stage kidney disease. Here, we investigated the anti-inflammatory activity of STS in our glial-mediated neuroinflammatory model.</p></sec><sec><title>Methods</title><p>Firstly, we measured glutathione (GSH) and hydrogen sulfide (H<sub>2</sub>S, SH<sup>−</sup>) levels in glial cells after treatment with sodium hydrosulfide (NaSH) or STS. We also measured released levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) from them. We used two cell viability assays, MTT and lactate dehydrogenase (LDH) release assays, to investigate glial-mediated neurotoxicity and anti-inflammatory effects of NaSH or STS. We also employed Western blot to examine activation of intracellular inflammatory pathways.</p></sec><sec><title>Results</title><p>We found that STS increases H<sub>2</sub>S and GSH expression in human microglia and astrocytes. When human microglia and astrocytes are activated by lipopolysaccharide (LPS)/interferon-γ (IFNγ) or IFNγ, they release materials that are toxic to differentiated SH-SY5Y cells. When the glial cells were treated with NaSH or STS, there was a significant enhancement of neuroprotection. The effect was concentration-dependent and incubation time-dependent. Such treatment reduced the release of TNFα and IL-6 and also attenuated activation of P38 MAPK and NFκB proteins. The compounds tested were not harmful when applied directly to all the cell types.</p></sec><sec><title>Conclusions</title><p>Although NaSH was somewhat more powerful than STS in these in vitro assays, STS has already been approved as an orally available treatment. STS may therefore be a candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s12974-016-0488-8) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hayden, Mr" uniqKey="Hayden M">MR Hayden</name></author><author><name sortKey="Goldsmith, Dj" uniqKey="Goldsmith D">DJ Goldsmith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berlin, Fr" uniqKey="Berlin F">FR Berlin</name></author><author><name sortKey="Baseler, Lj" uniqKey="Baseler L">LJ Baseler</name></author><author><name sortKey="Wilson, Cr" uniqKey="Wilson C">CR Wilson</name></author><author><name sortKey="Kritchevsky, Je" uniqKey="Kritchevsky J">JE Kritchevsky</name></author><author><name sortKey="Taylor, Sd" uniqKey="Taylor S">SD Taylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sakaguchi, M" uniqKey="Sakaguchi M">M Sakaguchi</name></author><author><name sortKey="Marutani, E" uniqKey="Marutani E">E Marutani</name></author><author><name sortKey="Shin, Hs" uniqKey="Shin H">HS Shin</name></author><author><name sortKey="Chen, W" uniqKey="Chen W">W Chen</name></author><author><name sortKey="Hanaoka, K" uniqKey="Hanaoka K">K Hanaoka</name></author><author><name sortKey="Xian, M" uniqKey="Xian M">M Xian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tokuda, K" uniqKey="Tokuda K">K Tokuda</name></author><author><name sortKey="Kida, K" uniqKey="Kida K">K Kida</name></author><author><name sortKey="Marutani, E" uniqKey="Marutani E">E Marutani</name></author><author><name sortKey="Crimi, E" uniqKey="Crimi E">E Crimi</name></author><author><name sortKey="Bougaki, M" uniqKey="Bougaki M">M Bougaki</name></author><author><name sortKey="Khatri, A" uniqKey="Khatri A">A Khatri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirozu, K" uniqKey="Shirozu K">K Shirozu</name></author><author><name sortKey="Tokuda, K" uniqKey="Tokuda K">K Tokuda</name></author><author><name sortKey="Marutani, E" uniqKey="Marutani E">E Marutani</name></author><author><name sortKey="Lefer, D" uniqKey="Lefer D">D Lefer</name></author><author><name sortKey="Wang, R" uniqKey="Wang R">R Wang</name></author><author><name sortKey="Ichinose, F" uniqKey="Ichinose F">F Ichinose</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sowers, Km" uniqKey="Sowers K">KM Sowers</name></author><author><name sortKey="Hayden, Mr" uniqKey="Hayden M">MR Hayden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sen, U" uniqKey="Sen U">U Sen</name></author><author><name sortKey="Vacek, Tp" uniqKey="Vacek T">TP Vacek</name></author><author><name sortKey="Hughes, Wm" uniqKey="Hughes W">WM Hughes</name></author><author><name sortKey="Kumar, M" uniqKey="Kumar M">M Kumar</name></author><author><name sortKey="Moshal, Ks" uniqKey="Moshal K">KS Moshal</name></author><author><name sortKey="Tyagi, N" uniqKey="Tyagi N">N Tyagi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sen, U" uniqKey="Sen U">U Sen</name></author><author><name sortKey="Basu, P" uniqKey="Basu P">P Basu</name></author><author><name sortKey="Abe, Oa" uniqKey="Abe O">OA Abe</name></author><author><name sortKey="Givvimani, S" uniqKey="Givvimani S">S Givvimani</name></author><author><name sortKey="Tyagi, N" uniqKey="Tyagi N">N Tyagi</name></author><author><name sortKey="Metreveli, N" uniqKey="Metreveli N">N Metreveli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bijarnia, Rk" uniqKey="Bijarnia R">RK Bijarnia</name></author><author><name sortKey="Bachtler, M" uniqKey="Bachtler M">M Bachtler</name></author><author><name sortKey="Chandak, Pg" uniqKey="Chandak P">PG Chandak</name></author><author><name sortKey="Van Goor, H" uniqKey="Van Goor H">H van Goor</name></author><author><name sortKey="Pasch, A" uniqKey="Pasch A">A Pasch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Cho, T" uniqKey="Cho T">T Cho</name></author><author><name sortKey="Jantaratnotai, N" uniqKey="Jantaratnotai N">N Jantaratnotai</name></author><author><name sortKey="Wang, Yt" uniqKey="Wang Y">YT Wang</name></author><author><name sortKey="Mcgeer, E" uniqKey="Mcgeer E">E McGeer</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author><author><name sortKey="Schwab, C" uniqKey="Schwab C">C Schwab</name></author><author><name sortKey="Parent, A" uniqKey="Parent A">A Parent</name></author><author><name sortKey="Doudet, D" uniqKey="Doudet D">D Doudet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Schwab, C" uniqKey="Schwab C">C Schwab</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S Yu</name></author><author><name sortKey="Mcgeer, E" uniqKey="Mcgeer E">E McGeer</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Sparatore, A" uniqKey="Sparatore A">A Sparatore</name></author><author><name sortKey="Del Soldato, P" uniqKey="Del Soldato P">P Del Soldato</name></author><author><name sortKey="Mcgeer, E" uniqKey="Mcgeer E">E McGeer</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Tazzari, V" uniqKey="Tazzari V">V Tazzari</name></author><author><name sortKey="Giustarini, D" uniqKey="Giustarini D">D Giustarini</name></author><author><name sortKey="Rossi, R" uniqKey="Rossi R">R Rossi</name></author><author><name sortKey="Sparatore, A" uniqKey="Sparatore A">A Sparatore</name></author><author><name sortKey="Del Soldato, P" uniqKey="Del Soldato P">P Del Soldato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singh, Us" uniqKey="Singh U">US Singh</name></author><author><name sortKey="Pan, J" uniqKey="Pan J">J Pan</name></author><author><name sortKey="Kao, Yl" uniqKey="Kao Y">YL Kao</name></author><author><name sortKey="Joshi, S" uniqKey="Joshi S">S Joshi</name></author><author><name sortKey="Young, Kl" uniqKey="Young K">KL Young</name></author><author><name sortKey="Baker, Km" uniqKey="Baker K">KM Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Mcgeer, E" uniqKey="Mcgeer E">E McGeer</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Encinas, M" uniqKey="Encinas M">M Encinas</name></author><author><name sortKey="Iglesias, M" uniqKey="Iglesias M">M Iglesias</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Muhaisen, A" uniqKey="Muhaisen A">A Muhaisen</name></author><author><name sortKey="Ce A, V" uniqKey="Ce A V">V Ceña</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Kang, Y" uniqKey="Kang Y">Y Kang</name></author><author><name sortKey="Suk, K" uniqKey="Suk K">K Suk</name></author><author><name sortKey="Schwab, C" uniqKey="Schwab C">C Schwab</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S Yu</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Suk, K" uniqKey="Suk K">K Suk</name></author><author><name sortKey="Kang, Y" uniqKey="Kang Y">Y Kang</name></author><author><name sortKey="Mcgeer, E" uniqKey="Mcgeer E">E McGeer</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hissin, Pj" uniqKey="Hissin P">PJ Hissin</name></author><author><name sortKey="Hilf, R" uniqKey="Hilf R">R Hilf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klegeris, A" uniqKey="Klegeris A">A Klegeris</name></author><author><name sortKey="Walker, Dg" uniqKey="Walker D">DG Walker</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hashioka, S" uniqKey="Hashioka S">S Hashioka</name></author><author><name sortKey="Klegeris, A" uniqKey="Klegeris A">A Klegeris</name></author><author><name sortKey="Monji, A" uniqKey="Monji A">A Monji</name></author><author><name sortKey="Kato, T" uniqKey="Kato T">T Kato</name></author><author><name sortKey="Sawada, M" uniqKey="Sawada M">M Sawada</name></author><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Wagoner, Nj" uniqKey="Van Wagoner N">NJ Van Wagoner</name></author><author><name sortKey="Benveniste, En" uniqKey="Benveniste E">EN Benveniste</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kimura, Y" uniqKey="Kimura Y">Y Kimura</name></author><author><name sortKey="Kimura, H" uniqKey="Kimura H">H Kimura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author><author><name sortKey="Mcgeer, Eg" uniqKey="Mcgeer E">EG McGeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Whitton, Ps" uniqKey="Whitton P">PS Whitton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kabil, O" uniqKey="Kabil O">O Kabil</name></author><author><name sortKey="Banerjee, R" uniqKey="Banerjee R">R Banerjee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olson, Kr" uniqKey="Olson K">KR Olson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Lee, Moonhee" sort="Lee, Moonhee" uniqKey="Lee M" first="Moonhee" last="Lee">Moonhee Lee</name><name sortKey="Mcgeer, Edith G" sort="Mcgeer, Edith G" uniqKey="Mcgeer E" first="Edith G." last="Mcgeer">Edith G. Mcgeer</name><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L." last="Mcgeer">Patrick L. Mcgeer</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000203 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000203 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:4746933
|texte= Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26856696" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |