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Near-infrared oligonucleotide duplex sensors for imaging rapidly activated transcription factors in vitro and in situ
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Paper Abstract

Pleiotropic and evolutionally conserved components of transcription nuclear factor - NF-B play key roles in progression of various diseases by regulating expression of antiapoptotic and cytokine responsive genes [1] [2]. We previously demonstrated that rapidly activating transcription factors (TF) can be detected by using sequence-specific self-quenched reporter probes (oligonucleotide-molecular sensors (ODN-MS), which ideally remain “silent” in the absence of activated TF but emit photons upon specific binding to them [3-5]. Recently we were investigating sensor-based optical imaging of early inflammation in the endocrine pancreas using type 1 diabetes (T1D) model because NF-κB activation is essential for determining the fate of pancreatic β-cells and hence the progression of T1D. Using an immunocompetent SKH1 mouse model of early stage T1D we showed that NF-κB activation was induced by low-dose streptozotocin (LD-STZ). ODNMS probes that carried near-infrared (NIR) fluorophores formed a complex with NF-κB subunits in in vitro assays and in situ after LD-STZ treatment. Imaging studies of pancreas (sections and isolated islets) were corroborated with electrophoresis mobility shift assays (EMSA). A higher specific NIR fluorescence intensity in nuclei and cytoplasm of islets from LD-STZ treated groups compared to non-treated control animals was observed. Our results demonstrate that: 1) the use of ODN-MS probes in non-fixed islets and tissue sections may be used for distinguishing differences in inflammatory pathway activation in animal models of early stage diabetes; 2) early, non-invasive detection of NF-κB in pancreatic islets may serve as a potential strategy for imaging of early T1D-mediated sustained pro-inflammatory changes in the endocrine pancreas.

Paper Details

Date Published: 1 March 2019
PDF: 11 pages
Proc. SPIE 10877, Dynamics and Fluctuations in Biomedical Photonics XVI, 1087702 (1 March 2019); doi: 10.1117/12.2511124
Show Author Affiliations
Alexei A. Bogdanov Jr., Univ. of Massachusetts Medical School (United States)
A.N. Bach Institute of Biochemistry (Russian Federation)
Valeriy G. Metelev, Univ. of Massachusetts Medical School (United States)
M.V. Lomonosov Moscow State Univ. (Russian Federation)
Toloo Taghian, Univ. of Massachusetts Medical School (United States)
Ilya Solovyev, A.N. Bach Institute of Biochemistry (Russian Federation)
Anand T. N. Kumar, Massachusetts General Hospital (United States)
Surong Zhang, Univ. of Massachusetts Medical School (United States)
Alexander Savitsky, M.V. Lomonosov Moscow State Univ. (Russian Federation)
A.N. Bach Institute of Biochemistry (Russian Federation)


Published in SPIE Proceedings Vol. 10877:
Dynamics and Fluctuations in Biomedical Photonics XVI
Valery V. Tuchin; Martin J. Leahy; Ruikang K. Wang, Editor(s)

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