ABSTRACT
Plasma membrane efflux transporters play crucial roles in the removal and release of both harmful and beneficial substances from the interior of cells and tissue types in virtually every extant species. They contribute to the clearance of a broad spectrum of exogenous and endogenous toxicants and harmful metabolites, including the reactive lipid aldehyde byproducts of lipid peroxidation that are a hallmark of cellular ageing. Here, we tested whether declining transporter functionality may contribute to functional decline in a snail model of neuronal ageing. Through measuring the removal of 5(6)-carboxyfluorescein, a known substrate for membrane efflux transporters, we provide, for the first time, physiological evidence for the existence of probenecid-, MK571- and glutathione-sensitive efflux transporters in (gastropod) neurons and demonstrate that their functionality declines with age. Our data support the idea that waning cellular detoxification capacity might be a significant factor in the escalation of (lipo-)toxicity observed in neuronal ageing.
FOOTNOTES
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: P.M.H., W.C.W.; Methodology: P.M.H., A.C.P.; Validation: P.M.H., W.C.W.; Formal analysis: P.M.H., W.C.W.; Data curation: P.M.H., A.C.P., I.H.; Writing - original draft: P.M.H., W.C.W.; Writing - review & editing: P.M.H., W.C.W.; Supervision: W.C.W.; Funding acquisition: W.C.W.
Funding
The work was supported by a National Science and Engineering Research Council of Canada (NSERC) operating grant to W.C.W.
- Received September 3, 2019.
- Accepted January 6, 2020.
- © 2020. Published by The Company of Biologists Ltd
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