Rhenium(I) Conjugates As Tools for Tracking Cholesterol in Cells

Overview

Journal Metallomics

Publisher Oxford University Press

Date 2022 Jun 3

PMID 35657681

Authors

Joanna Lazniewska

Christie Bader

Shane M Hickey

Stavros Selemidis

John OLeary

Peter V Simpson

Stefano Stagni

Sally E Plush

Massimiliano Massi

Doug Brooks

Affiliations

Soon will be listed here.

Abstract

Cholesterol is vital to control membrane integrity and fluidity, but is also a precursor to produce steroid hormones, bile acids, and vitamin D. Consequently, altered cholesterol biology has been linked to many diseases, including metabolic syndromes and cancer. Defining the intracellular pools of cholesterol and its trafficking within cells is essential to understand both normal cell physiology and mechanisms of pathogenesis. We have synthesized a new cholesterol mimic (ReTEGCholestanol), comprising a luminescent rhenium metal complex and a cholestanol targeting unit, linked using a tetraethylene glycol (TEG) spacer. ReTEGCholestanol demonstrated favourable imaging properties and improved water solubility when compared to a cholesterol derivative, and structurally related probes lacking the TEG linker. A non-malignant and three malignant prostate cell lines were used to characterize the uptake and intracellular distribution of ReTEGCholestanol. The ReTEGCholestanol complex was effectively internalized and mainly localized to late endosomes/lysosomes in non-malignant PNT1a cells, while in prostate cancer cells it also accumulated in early endosomes and multivesicular bodies, suggesting disturbed cholesterol biology in the malignant cells. The ReTEGCholestanol is a novel imaging agent for visualizing endosomal uptake and trafficking, which may be used to define cholesterol related biology including membrane integration and altered lipid trafficking/processing.

Citing Articles

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications.

Lee L, Lo K Chem Rev. 2024; 124(15):8825-9014.

PMID: 39052606 PMC: 11328004. DOI: 10.1021/acs.chemrev.3c00629.

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