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PMID:17408620

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Citation

Engel, T, Kannenberg, F, Fobker, M, Nofer, JR, Bode, G, Lueken, A, Assmann, G and Seedorf, U (2007) Expression of ATP binding cassette-transporter ABCG1 prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol. FEBS Lett. 581:1673-80

Abstract

Oxysterols result from cholesterol by enzymatic or oxidative processes. Some exert cytotoxic effects leading to necrosis or apoptosis. Detoxification of these compounds mainly occurs in the liver and requires transport from peripheral tissues towards it. Some ATP-binding cassette transporters are involved in export of cytotoxic compounds. In the current study, we investigated whether ABC transporter family member G1 (ABCG1) may be involved in oxysterol transport, since its gene expression is highly responsive to oxysterol loading. TetOff HeLa cells stably expressing ABCG1 showed decreased mass uptake of 7beta-hydroxycholesterol (7beta-HC) whereas that of other physiologically relevant oxysterols was unaffected. Application of 7beta-HC to ABCG1 expressing cells induced hyperpolarization of mitochondrial membrane potential and production of reactive oxygen species, indicating energy consumption by the ATP-binding cassette transporter when it is activated by its correct substrate. Our study points to detoxification as one of potential cellular functions of ABCG1. We assume that ABCG1 protects against 7beta-HC-induced cell death, an important role in prevention of neurodegenerative and cardiovascular disease.

Links

PubMed Online version:10.1016/j.febslet.2007.03.038

Keywords

ATP-Binding Cassette Transporters/genetics; ATP-Binding Cassette Transporters/metabolism; Apoptosis; Biological Transport; Cardiovascular Diseases/etiology; Cell Death; HeLa Cells; Humans; Hydroxycholesterols/metabolism; Membrane Potentials; Mitochondrial Membranes/metabolism; Mitochondrial Membranes/physiology; Neurodegenerative Diseases/etiology; Reactive Oxygen Species/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ABCG1

enables

GO:0034041: ATPase-coupled sterol transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ABCG1

enables

GO:0034041: sterol-transporting ATPase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ABCG1

enables

GO:0019534: toxin transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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