Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes.

Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes. Research Abstract Details 

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Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes. Abstract Text:

A Sigruener,C Buechler,E ,A Hartmann,P J Wild,L Terracciano,M Roncalli,S R Bornstein,G Schmitz,A Sigruener,C Buechler,E ,A Hartmann,P J Wild,L Terracciano,M Roncalli,S R Bornstein,G Schmitz,A Sigruener,C Buechler,E Orsó,A Hartmann,P J Wild,L Terracciano,M Roncalli,S R Bornstein,G Schmitz,

AOX1, a member of the cytosolic molybdenum hydroxylase family, has been identified by us earlier as an ABCA1-interacting protein. AOX1 is well-described as xenobiotic metabolizing enzyme, which upon oxidation of acetaldehyde and retinaldehyde to acetic acid and retinoic acid generates reactive oxygen species. Here we show that knock-down of AOX1 in HepG2 by small interfering RNA significantly reduced ABCA1-dependent lipid efflux and enhanced phagocytic uptake of microspheres similar to ABCA1 deficiency, without affecting ABCA1 mRNA and protein levels. ABCA1 and AOX1 are coexpressed in human hepatocytes, kidney proximal tubular epithelial cells, Leydig, and adrenocortical cells. Expression of ABCA1 and AOX1 was investigated by immunohistochemistry in liver tissue arrays. A strong AOX1 expression was found in normal liver, and in cirrhosis. In contrast, hepatocellular carcinomas showed either a complete loss or reduced expression of AOX1. Significant correlations were found between reduced AOX1 expression and tumor stage, or metastatic or regional lymph node states. Deregulation was also observed for ABCA1 expression but to a lesser extent. Our findings show that the interaction of ABCA1 with AOX1 modulates ABCA1-linked cellular functions such as lipid efflux and phagocytosis in hepatocytes, and the reduced expression of AOX1 in malignant transformed hepatocytes supports the differentiation dependent upregulation of AOX1.

Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes. Publishing Authors By Initials

A Sigruener,C Buechler,E ,A Hartmann,PJ Wild,L Terracciano,M Roncalli,SR Bornstein,G Schmitz,A Sigruener,C Buechler,E ,A Hartmann,PJ Wild,L Terracciano,M Roncalli,SR Bornstein,G Schmitz,A Sigruener,C Buechler,E Orsó,A Hartmann,PJ Wild,L Terracciano,M Roncalli,SR Bornstein,G Schmitz,

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Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hormone and metabolic research. Hormon- und Stoffw

VOLUME: 39

Page Numbers: 781-9

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ISSN: 0018-5043

DAY: 9

MONTH: Nov

YEAR: 2007

Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes. Information

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LANGUAGE: eng

NlmUniqueID: 177722

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Grant and Affiliation Information for Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes.

AFFILIATION: 1Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Regensburg, Germany.

Country: Germany

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MEDLINETA: Horm Metab Res

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