Biomedical Engineering Reference
In-Depth Information
Group1
Run 1
Run 2
Oat1
Oat3
10
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1
10
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1
10
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3
10
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3
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5
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10
SGLT1
NaPi-2
10
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1
10
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1
10
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3
10
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3
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FIGURE 4.3.
Relative gene expression levels of OAT genes in embryonic kidney as deter-
mined by QPCR, illustrating the up-regulation of SLC family genes as rat kidney maturation
progresses. Data were normalized to the expression of glyceraldehyde-3-phosphate dehydroge-
nase in the same sample and are reported as the ratio of the level of normalized gene expression
in the sample of interest to the level of gene expression in adult kidney (mean values
±
S.D.).
(From ref. 29.)
expression patterns of OAT1, OAT3, SGLT1, and NaPi2 were found to closely resem-
ble those observed in vivo.
29
Moreover, using fluorescein uptake as an in vitro func-
tional assay of OAT expression, inhibition of fluorescein accumulation by probenecid
was observed within the tubular structures of the cultured organs.
29
Together with
the expression studies, these findings indicate not only that the OATs are expressed
functionally during kidney development and might be markers of proximal tubule
differentiation, but also raise the possibility that these organ culture systems may
represent convenient and reliable in vitro models for study of the developmental in-
duction of the OATs. Given the increasingly lower gestational ages at which infants
are being delivered, these types of studies may eventually shed light on the ability of
kidneys in premature babies to handle drugs and toxins.
4.4. STRUCTURE AND FUNCTION OF OATs
Although OATs are thought to be similar to other MFS transporters, having 12
α
-helical transmembrane domains (TMDs) as well as functional similarity, the crys-
tal structure of OATs is not known, and hence their transport mechanism remains
unclear. However, close examination of the primary structure reveals integral clues;
weak sequence homology between the two six-helix halves suggests that MFS pro-
teins originated from the duplication of a six-TMD ancestor.
8
,
32
There are two large
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