2P-0448 Two prevalent mutations in the ATP-binding cassette transporters ABCC6 Japanese patients with pseudoxanthoma elasticum (PXE)

Hematopoietic cells express ATP binding cassette (ABC) transporters in relation to different degrees of differentiation. One of the known multidrug resistance mechanisms in acute myeloid leukemia (AML) is the overexpression of efflux pumps belonging to the superfamily of ABC transporters such as ABCB1, ABCG2 and ABCC1. Although several studies were carried out to correlate ABC transporters expression with drug resistance, little is known about their role as markers of diagnosis and progression of the disease. For this purpose we investigated the expression, by real-time PCR, of some ABC genes in bone marrow samples of AML patients at diagnosis and after induction therapy. At diagnosis, ABCG2 was always down-regulated, while an up regulated trend for ABCC1 was observed. After therapy the examined genes showed a different expression trend and approached the values of healthy subjects suggesting that this event could be considered as a marker of AML regression. The expression levels of some ABC transporters such as ABCC6, seems to be related to gender, age and to the presence of FLT3/ITD gene mutation.

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Stickleback embryos use ATP-binding cassette transporters as a buffer against exposure to maternally derived cortisol

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2838 ◽

2016 ◽

Vol 283 (1826) ◽

pp. 20152838 ◽

Cited By ~ 17

Author(s):

Ryan T. Paitz ◽

Syed Abbas Bukhari ◽

Alison M. Bell

Keyword(s):

Abc Transporters ◽

Gasterosteus Aculeatus ◽

Transcriptional Response ◽

Threespine Stickleback ◽

Egg Laying ◽

Atp Binding ◽

Active Efflux ◽

Atp Binding Cassette Transporters ◽

Stress Influences ◽

Atp Binding Cassette

Offspring from females that experience stressful conditions during reproduction often exhibit altered phenotypes and many of these effects are thought to arise owing to increased exposure to maternal glucocorticoids. While embryos of placental vertebrates are known to regulate exposure to maternal glucocorticoids via placental steroid metabolism, much less is known about how and whether egg-laying vertebrates can control their steroid environment during embryonic development. We tested the hypothesis that threespine stickleback ( Gasterosteus aculeatus ) embryos can regulate exposure to maternal steroids via active efflux of maternal steroids from the egg. Embryos rapidly (within 72 h) cleared intact steroids, but blocking ATP-binding cassette (ABC) transporters inhibited cortisol clearance. Remarkably, this efflux of cortisol was sufficient to prevent a transcriptional response of embryos to exogenous cortisol. Taken together, these findings suggest that, much like their placental counterparts, developing fish embryos can actively regulate their exposure to maternal cortisol. These findings highlight the fact that even in egg-laying vertebrates, the realized exposure to maternal steroids is mediated by both maternal and embryonic processes and this has important implications for understanding how maternal stress influences offspring development.

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