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Sökning: WFRF:(Scharfmann R) > Imatinib mesilate-i...

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FältnamnIndikatorerMetadata
00005053naa a2200445 4500
001oai:DiVA.org:uu-196342
003SwePub
008130308s2013 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1963422 URI
0247 a https://doi.org/10.1007/s00125-013-2868-22 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Mokhtari, Dariushu Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)damok087
2451 0a Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells :b role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl
264 c 2013-03-05
264 1b Springer Science and Business Media LLC,c 2013
338 a electronic2 rdacarrier
520 a AIMS/HYPOTHESIS: It is not clear how small tyrosine kinase inhibitors, such as imatinib mesilate, protect against diabetes and beta cell death. The aim of this study was to determine whether imatinib, as compared with the non-cAbl-inhibitor sunitinib, affects pro-survival signalling events in the phosphatidylinositol 3-kinase (PI3K) pathway. METHODS: Human EndoC-βH1 cells, murine beta TC-6 cells and human pancreatic islets were used for immunoblot analysis of insulin receptor substrate (IRS)-1, Akt and extracellular signal-regulated kinase (ERK) phosphorylation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] plasma membrane concentrations were assessed in EndoC-βH1 and MIN6 cells using evanescent wave microscopy. Src homology 2-containing inositol 5'-phosphatase 2 (SHIP2) tyrosine phosphorylation and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) serine phosphorylation, as well as c-Abl co-localisation with SHIP2, were studied in HEK293 and EndoC-βH1 cells by immunoprecipitation and immunoblot analysis. Gene expression was assessed using RT-PCR. Cell viability was measured using vital staining. RESULTS: Imatinib stimulated ERK(thr202/tyr204) phosphorylation in a c-Abl-dependent manner. Imatinib, but not sunitinib, also stimulated IRS-1(tyr612), Akt(ser473) and Akt(thr308) phosphorylation. This effect was paralleled by oscillatory bursts in plasma membrane PI(3,4,5)P3 levels. Wortmannin induced a decrease in PI(3,4,5)P3 levels, which was slower in imatinib-treated cells than in control cells, indicating an effect on PI(3,4,5)P3-degrading enzymes. In line with this, imatinib decreased the phosphorylation of SHIP2 but not of PTEN. c-Abl co-immunoprecipitated with SHIP2 and its binding to SHIP2 was largely reduced by imatinib but not by sunitinib. Imatinib increased total β-catenin levels and cell viability, whereas sunitinib exerted negative effects on cell viability. CONCLUSIONS/INTERPRETATION: Imatinib inhibition of c-Abl in beta cells decreases SHIP2 activity, which results in enhanced signalling downstream of PI3 kinase.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
7001 a Al-Amin, Abdullahu Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)abdal875
7001 a Turpaev, Kyrill4 aut
7001 a Li, Tingtingu Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab4 aut
7001 a Idevall-Hagren, Olofu Uppsala universitet,Institutionen för medicinsk cellbiologi4 aut0 (Swepub:uu)olide169
7001 a Li, Jiau Uppsala universitet,Institutionen för medicinsk cellbiologi4 aut0 (Swepub:uu)jiali219
7001 a Wuttke, Anneu Uppsala universitet,Institutionen för medicinsk cellbiologi4 aut0 (Swepub:uu)annwu514
7001 a Fred, Rikard Gu Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)rifre425
7001 a Ravassard, Philippe4 aut
7001 a Scharfmann, R4 aut
7001 a Tengholm, Andersu Uppsala universitet,Institutionen för medicinsk cellbiologi4 aut0 (Swepub:uu)andeteng
7001 a Welsh, Nilsu Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)nilswels
7102 a Uppsala universitetb Institutionen för medicinsk cellbiologi4 org
7730 t Diabetologiad : Springer Science and Business Media LLCg 56:6, s. 1327-1338q 56:6<1327-1338x 0012-186Xx 1432-0428
8564 u https://uu.diva-portal.org/smash/get/diva2:609926/FULLTEXT04.pdfx primaryx Raw objecty fulltext:preprint
8564 u https://link.springer.com/content/pdf/10.1007%2Fs00125-013-2868-2.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-196342
8564 8u https://doi.org/10.1007/s00125-013-2868-2

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