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Interleukin-18 alte...
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Sutinen, Elina M.
(författare)
Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells
- Artikel/kapitelEngelska2014
Förlag, utgivningsår, omfång ...
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2014-08-07
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Frontiers Media SA,2014
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-230949
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-230949URI
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https://doi.org/10.3389/fncel.2014.00214DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-beta (A beta) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3?, as well as A beta-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other IL-18 regulated proteins in neuron-like SH-SY5Y cells. Differentiated SH-SY5Y cells, incubated with IL-18 for 24, 48, or 72 h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE). Specific altered protein spots were chosen and identified with mass spectrometry (MS) and verified by western immunoblotting (WIB). IL-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous protein levels/modifications. We concentrated on those related to OS (DDAH2, peroxiredoxins 2, 3, and 6, DJ-1, BLVRA), A beta-degradation (MMP14, TIMP2), A beta-aggregation (Septin-2), and modifications of axon growth and guidance associated, collapsin response mediator protein 2 (CRMP2). IL-18 significantly increased antioxidative enzymes, indicative of OS, and altered levels of glycolytic beta- and alpha-enolase and multifunctional 14-3-3 beta and -beta, commonly affected in neurodegenerative diseases. MMP14, TIMP2, alpha-enolase and 14-3-3 beta, indirectly involved in A? metabolism, as well as Septin-2 showed changes that increase A? levels. Increased 14-3-3 beta may contribute to GSK3 beta driven tau hyperphosphorylation and CRMP2 Thr514 and Ser522 phosphorylation with the Thr555-site, a target for Rho kinase, showing time-dependent changes. IL-18 also increased caspase-1 levels and vacuolization of the cells. Although our SH-SY5Y cells were not aged, as neurons in AD, our work suggests that heightened or prolonged IL-18 levels can drive protein changes of known relevance to AD pathogenesis.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Korolainen, Minna A.
(författare)
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Hayrinen, Jukka
(författare)
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Alafuzoff, IrinaUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)irial548
(författare)
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Petratos, Steven
(författare)
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Salminen, Antero
(författare)
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Soininen, Hilkka
(författare)
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Pirttila, Tuula
(författare)
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Ojala, Johanna O.
(författare)
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Uppsala universitetMolekylär och morfologisk patologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Frontiers in Cellular Neuroscience: Frontiers Media SA8, s. 214-1662-5102
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