Imaging NF-κB activity in a murine model of early stage diabetesстатья

Статья опубликована в высокорейтинговом журнале

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Дата последнего поиска статьи во внешних источниках: 28 февраля 2020 г.

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1. Полный текст Taghian_Imaging_NF-kB_activity_FASEB.pdf 1,3 МБ 9 января 2020 [MetelevV]

[1] Imaging nf-κb activity in a murine model of early stage diabetes / T. Toloo, V. G. Metelev, Z. Surong, A. B. J. Alexei // FASEB Journal. — 2020. — Vol. 34. — P. 1198–1210. Early pro-inflammatory signaling in the endocrine pancreas involves activation of NF-κB, which is believed to be important for determining the ultimate fate of β-cells and hence progression of type 1 diabetes (T1D). Thus, early non-invasive detection of NF-κB in pancreatic islets may serve as a potential strategy for monitoring early changes in pancreatic endocrine cells eventually leading to T1D. We investigated the feasibility of optical imaging of NF-κB transcription factor activation induced by low-dose streptozocin (LD-STZ) treatment in the immunocompetent SKH1 mouse model of early stage diabetes. In this model, we showed that the levels of NF-κB may be visualized and measured by fluorescence intensity of specific near-infrared (NIR) fluorophore-labeled oligodeoxyribonucleotide duplex (ODND) probes. In addition, NF-κB activation following LD-STZ treatment was validated using immunofluorescence and transgenic animals expressing NF-κB inducible imaging reporter. We showed that LD-STZ-treated SKH1 mice had significantly higher (2-3 times, P < .01) specific NIR FI in the nuclei and cytoplasm of islets cells than in non-treated control mice and this finding was corroborated by immunoblotting and electrophoretic mobility shift assays. Finally, using semi-quantitative confocal analysis of nonfixed pancreatic islet microscopy we demonstrated that ODND probes may be used to distinguish between the islets with high levels of NF-κB transcription factor and control islet cells. [ DOI ]

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