ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells
In addition to sphingomyelin and ceramide, sugar derivatives of ceramides, hexosylceramides (HexCer) are the major circulating sphingolipids. We have shown that silencing of ABCA1 transmembrane protein function for instance in cases of loss of function of ABCA1 gene results in low levels of HDL as w...
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MDPI AG
2022-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/20/4401 |
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| author | Jahangir Iqbal Meghan T. Walsh M. Mahmood Hussain |
| author_facet | Jahangir Iqbal Meghan T. Walsh M. Mahmood Hussain |
| author_sort | Jahangir Iqbal |
| collection | DOAJ |
| description | In addition to sphingomyelin and ceramide, sugar derivatives of ceramides, hexosylceramides (HexCer) are the major circulating sphingolipids. We have shown that silencing of ABCA1 transmembrane protein function for instance in cases of loss of function of ABCA1 gene results in low levels of HDL as well as a concomitant reduction in plasma HexCer levels. However, proteins involved in hepatic synthesis and egress of HexCer from cells is not well known although ABCA1 seems to be indirectly controlling the HexCer plasma levels by supporting HDL synthesis. In this study, we hypothesized that protein(s) other than ABCA1 are involved in the transport of HexCer to HDL. Using an unbiased knockdown approach, we found that ATP-binding cassette transporter protein C10 (ABCC10) participates in the synthesis of HexCer and thereby affects egress to HDL in human hepatoma Huh-7 cells. Furthermore, livers from ABCC10 deficient mice had significantly lower levels of HexCer compared to wild type livers. These studies suggest that ABCC10 partakes in modulating the synthesis and subsequent efflux of HexCer to HDL in liver cells. |
| first_indexed | 2024-03-09T19:38:34Z |
| format | Article |
| id | doaj.art-090412b1a04b47e581a5a1bafdc533f3 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T19:38:34Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-090412b1a04b47e581a5a1bafdc533f32023-11-24T01:46:11ZengMDPI AGNutrients2072-66432022-10-011420440110.3390/nu14204401ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver CellsJahangir Iqbal0Meghan T. Walsh1M. Mahmood Hussain2Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USADepartment of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USADepartment of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USAIn addition to sphingomyelin and ceramide, sugar derivatives of ceramides, hexosylceramides (HexCer) are the major circulating sphingolipids. We have shown that silencing of ABCA1 transmembrane protein function for instance in cases of loss of function of ABCA1 gene results in low levels of HDL as well as a concomitant reduction in plasma HexCer levels. However, proteins involved in hepatic synthesis and egress of HexCer from cells is not well known although ABCA1 seems to be indirectly controlling the HexCer plasma levels by supporting HDL synthesis. In this study, we hypothesized that protein(s) other than ABCA1 are involved in the transport of HexCer to HDL. Using an unbiased knockdown approach, we found that ATP-binding cassette transporter protein C10 (ABCC10) participates in the synthesis of HexCer and thereby affects egress to HDL in human hepatoma Huh-7 cells. Furthermore, livers from ABCC10 deficient mice had significantly lower levels of HexCer compared to wild type livers. These studies suggest that ABCC10 partakes in modulating the synthesis and subsequent efflux of HexCer to HDL in liver cells.https://www.mdpi.com/2072-6643/14/20/4401ABCA1sphingolipidsHDLglucosylceramideceramidesphingomyelin |
| spellingShingle | Jahangir Iqbal Meghan T. Walsh M. Mahmood Hussain ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells Nutrients ABCA1 sphingolipids HDL glucosylceramide ceramide sphingomyelin |
| title | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells |
| title_full | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells |
| title_fullStr | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells |
| title_full_unstemmed | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells |
| title_short | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells |
| title_sort | atp binding cassette transporter family c protein 10 participates in the synthesis and efflux of hexosylceramides in liver cells |
| topic | ABCA1 sphingolipids HDL glucosylceramide ceramide sphingomyelin |
| url | https://www.mdpi.com/2072-6643/14/20/4401 |
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