Rhenium(I) conjugates as tools for tracking cholesterol in cells.

Cholesterol endosomal pathway luminescence prostate cancer rhenium(I) complex

Journal

Metallomics : integrated biometal science
ISSN: 1756-591X
Titre abrégé: Metallomics
Pays: England
ID NLM: 101478346

Informations de publication

Date de publication:
02 08 2022
Historique:
received: 17 03 2022
accepted: 17 05 2022
pubmed: 4 6 2022
medline: 4 8 2022
entrez: 3 6 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35657681
pii: 6601455
doi: 10.1093/mtomcs/mfac040
pmc: PMC9344854
pii:
doi:

Substances chimiques

Rhenium 7440-15-5
Cholesterol 97C5T2UQ7J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press.

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Auteurs

Joanna Lazniewska (J)

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.

Christie Bader (C)

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.

Shane M Hickey (SM)

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.

Stavros Selemidis (S)

Department of Human Biosciences, RMIT University, Melbourne, Victoria 3000, Australia.

John O'Leary (J)

Discipline of Histopathology, University of Dublin Trinity College, Dublin 2, Ireland.

Peter V Simpson (PV)

School of Molecular and Life Sciences - Curtin University, Bentley, Western Australia 6102, Australia.

Stefano Stagni (S)

Department of Industrial Chemistry Toso Montanari, University of Bologna, Via Zamboni, 33, Bologna I-40136, Italy.

Sally E Plush (SE)

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.

Massimiliano Massi (M)

School of Molecular and Life Sciences - Curtin University, Bentley, Western Australia 6102, Australia.

Doug Brooks (D)

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Discipline of Histopathology, University of Dublin Trinity College, Dublin 2, Ireland.
School of Molecular and Life Sciences - Curtin University, Bentley, Western Australia 6102, Australia.

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Classifications MeSH