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

Toloo, T.; Metelev, V.G.; Surong, Z.; Alexei, A.B.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Web of Science, Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 28 февраля 2020 г.

Авторы: Toloo Taghian, Metelev Valeriy G., Surong Zhang, Alexei A.Bogdanov Jr
Журнал: FASEB Journal
Том: 34
Год издания: 2020
Издательство: Federation of American Societies for Experimental Biology
Местоположение издательства: United States
Первая страница: 1198
Последняя страница: 1210
DOI: 10.1096/fj.201801147R
Аннотация: Early pro-inflammatory signaling in the endocrine pancreas involves activation ofNF-κB, which is believed to be important for determining the ultimate fate of β-cellsand hence progression of type 1 diabetes (T1D). Thus, early non-invasive detectionof NF-κB in pancreatic islets may serve as a potential strategy for monitoring earlychanges in pancreatic endocrine cells eventually leading to T1D. We investigatedthe feasibility of optical imaging of NF-κB transcription factor activation induced bylow-dose streptozocin (LD-STZ) treatment in the immunocompetent SKH1 mousemodel of early stage diabetes. In this model, we showed that the levels of NF-κBmay 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-treatedcontrol 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 usedto distinguish between the islets with high levels of NF-κB transcription factor andcontrol islet cells.
Добавил в систему: Метелев Валерий Георгиевич

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

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