Biomedical Engineering Reference
In-Depth Information
homolog.
20
,
35
Furthermore, correlation of the expression data from one physiological
system may not correlate with another. Consequently, great care should be taken in
discerning too much from the data and extrapolating to other physiological models.
PepT1 is expressed primarily in small intestinal epithelial cells, the S1 (pars con-
voluta) segment of renal proximal tubules, hepatic bile duct epithelial cells, and
the pancreas.
13
,
35
-
38
Localization studies have also demonstrated that PepT1 is ex-
pressed to a lesser extent in the kidney, placenta, and prostate, while in the small
intestine, expression is maximal in the duodenum.
35
Ogihara et al. further demon-
strated PepT1 localization to the apical plasma membrane of enterocytes in rats.
39
Interestingly, PepT1 expression decreases along the descending small intestinal seg-
ments, with ileal expression appearing to be lower than jejunal.
35
Recently, Terada
et al. demonstrated that PepT1 is also relatively highly expressed in the stomach of
cancer patients, although interindividual differences were apparent.
40
Interestingly,
histological results suggest that gastric PepT1 may originate from intestinal metapla-
sia, which is characterized by the transdifferentiation of gastric epithelial cells to an
intestinal phenotype.
40
The functional and subsequent regulatory significance of this
expression remains to be elucidated.
Additional studies have demonstrated the intracellular localization of PepT1 iso-
forms to lysosomal compartments of renal tubular cells.
41
,
42
The functional signifi-
cance of this finding remains to be fully elucidated, although it is surmised that PepT1
may prevent accumulation of di- and tripeptides in renal lysosomes by transporting
substrates to the cytosolic compartment for subsequent hydrolysis.
41
Of note is the fact
that the apical expression of PepT1 has been well established in both prenatal and ma-
ture animals,
43
,
44
although the cellular localization does vary and is highly regulated.
Interestingly, PepT2 is more widely expressed than PepT1, with primary expres-
sion in the S2 and S3 segments of the apical membranes in renal proximal tubular
cells (pars recta), brain astrocytes, epithelial cells of choroids plexus, retina, mam-
mary gland, and bronchial epithelial cells.
36
,
45
-
48
The cloned human PepT2 cDNA
is 2190 bp long, encoding a predicted protein of 729 amino acids that shares approx-
imately 50% identity and 70% similarity with its corresponding PepT1 ortholog.
18
The gene encoding PepT2 has been mapped to chromosome 3q13.3-q21.
49
In vitro
translation of rabbit PepT2 cRNA resulted in an unglyosylated 83-kDa product and a
core-glycosylated 107-kDa product.
50
PepT2 mRNA expression has been identified
in human,
18
rat,
51
mouse,
52
and rabbit.
50
PepT2 was first identified due to the functional assessment that the renal peptide
transport system was similar but not identical to its intestinal counterpart (PepT1).
18
In fact, Liu et al. identified PepT2 by screening a human kidney cDNA library with a
probe derived from the rabbit intestinal PepT1 cDNA.
18
Since its first identification
and characterization, considerable research has been focused on elucidating the func-
tional expression and activity of PepT2 in the kidney. Moreover, recent studies have
hypothesized that its primary role is the active reabsorption (secretion) of renally
eliminated small oligopeptides.
53
While the expression of both PepT1 and PepT2
have been demonstrated in the proximal tubules of microdissected rat nephrons, all
other renal sections were negative for their expression.
36
The positive expression of
PepT1 and PepT2 in proximal tubules correlated with in vivo uptake of a fluorescent
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