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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Gastrointest+Liver+Physiol
2013 ; 304
(12
): G1079-86
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Glyoxalate reductase/hydroxypyruvate reductase interacts with the
sodium-dependent vitamin C transporter-1 to regulate cellular vitamin C
homeostasis
#MMPMID23599041
Subramanian VS
; Nabokina SM
; Patton JR
; Marchant JS
; Moradi H
; Said HM
Am J Physiol Gastrointest Liver Physiol
2013[Jun]; 304
(12
): G1079-86
PMID23599041
show ga
The human sodium-dependent vitamin C transporter 1 (hSVCT1) contributes to
cellular uptake of ascorbic acid (AA). Although different aspects of hSVCT1 cell
biology have been extensively studied, nothing is currently known about the
broader hSVCT1 interactome that modulates its role in cellular physiology. Here,
we identify the enzyme human glyoxalate reductase/hydroxypyruvate reductase
(hGR/HPR) as an hSVCT1 associated protein by yeast two-hybrid (Y2H) screening of
a human liver cDNA library. The interaction between hSVCT1 and hGR/HPR was
further confirmed by in vitro GST pull-down assay, in vivo coimmunoprecipitation
and mammalian two-hybrid firefly luciferase assays. This interaction had
functional significance as coexpression of hGR/HPR with hSVCT1 led to an increase
in AA uptake. Reciprocally, siRNA-mediated knockdown of endogenous hGR/HPR led to
an inhibition of AA uptake. Given that oxalate is a degradation product of
vitamin C and hGR/HPR acts to limit cellular oxalate levels, this association
physically couples two independent regulators of cellular oxalate production.
Furthermore, confocal imaging of human liver HepG2 cells coexpressing GFP-hSVCT1
and hGR/HPR-mCherry demonstrated that these two proteins colocalize within a
subpopulation of intracellular organelles. This provides a possible molecular
basis for organellar AA transport and regulation of local glyoxylate/glycolate
concentration in the vicinity of organelle membranes.