In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease.

Abstract:

:Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay between copper status, health, and disease in the same living organism over time. Here, we present the synthesis, characterization, and in vivo imaging applications of Copper-Caged Luciferin-1 (CCL-1), a bioluminescent reporter for tissue-specific copper visualization in living animals. CCL-1 uses a selective copper(I)-dependent oxidative cleavage reaction to release d-luciferin for subsequent bioluminescent reaction with firefly luciferase. The probe can detect physiological changes in labile Cu+ levels in live cells and mice under situations of copper deficiency or overload. Application of CCL-1 to mice with liver-specific luciferase expression in a diet-induced model of nonalcoholic fatty liver disease reveals onset of hepatic copper deficiency and altered expression levels of central copper trafficking proteins that accompany symptoms of glucose intolerance and weight gain. The data connect copper dysregulation to metabolic liver disease and provide a starting point for expanding the toolbox of reactivity-based chemical reporters for cell- and tissue-specific in vivo imaging.

authors

Heffern MC,Park HM,Au-Yeung HY,Van de Bittner GC,Ackerman CM,Stahl A,Chang CJ

doi

10.1073/pnas.1613628113

subject

Has Abstract

pub_date

2016-12-13 00:00:00

pages

14219-14224

issue

50

eissn

0027-8424

issn

1091-6490

pii

1613628113

journal_volume

113

pub_type

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