57 research outputs found
Functional Induction of the Cystine-Glutamate Exchanger System Xc- Activity in SH-SY5Y Cells by Unconjugated Bilirubin
We have previously reported that exposure of SH-SY5Y neuroblastoma cells to unconjugated bilirubin (UCB) resulted in a marked up-regulation of the mRNA encoding for the Na+ -independent cystine∶glutamate exchanger System Xc− (SLC7A11 and SLC3A2 genes). In this study we demonstrate that SH-SY5Y cells treated with UCB showed a higher cystine uptake due to a significant and specific increase in the activity of System Xc−, without the contribution of the others two cystine transporters (XAG− and GGT) reported in neurons. The total intracellular glutathione content was 2 folds higher in the cells exposed to bilirubin as compared to controls, suggesting that the internalized cystine is used for gluthathione synthesis. Interestingly, these cells were significantly less sensitive to an oxidative insult induced by hydrogen peroxide. If System Xc− is silenced the protection is lost. In conclusion, these results suggest that bilirubin can modulate the gluthathione levels in neuroblastoma cells through the induction of the System Xc−, and this renders the cell less prone to oxidative damage
Amino acid transport systems of lysosomes: Possible substitute utility of a surviving transport system for one congenitally defective or absent
Ways in which other transport systems may compensate for one that is genetically defective are considered. Comparisons of the transport systems of organelles (here the lysosome) with the transport system at the plasma membrane has significant implications for chemotherapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44194/1/10540_2005_Article_BF01116456.pd
A stereoselective anomaly in dicarboxylic amino acid transport
Using L-cysteate and tcysteinesulfinate as model
substrates, we characterize here a transport system,
both in culturerda t hepatocytes and human skin fibroblasts,
serving for thea nions glutamate and aspartate,
but not for the dipolar species glutamic and aspartic
acids. This system appears to be accompanied by a
second, lower affinity system for the anionic forms,
which is also Na’-dependent; this lower affinity system
applies at least to glutamate. These systems show the
usual degree of preference for L- over D-glutamate and,
in the fibroblast, for L- over DL-a-aminoadipate. D-ASpartate
proved nearly as inhibitory to the uptake of Lcysteate
or t-aspartate, however, as did L-aspartate
itself, a comparison recalling a similar stereoselective
anomaly discovered by Pall in Neurospora (Pall, M.
(1976) Biochim Biophys. Acta 211, 513-520). We conclude
that this anomaly arises from the ability of the
two substrate carboxylate groups tob ond in the spatial
order eithera # for the L-isomer or &a for the D-isomer
and also to bond in the order a,y for L-glutamate, but
scarcely in the order y,a for D-glutamate. A major lack
of inhibition by D-cysteate, whichm ight be expected to
bind like aspartate in the inverted order, shows, however,
that thetw o anionic groups are not recognized in
identical manners by the two corresponding subsites,
Precedent for a chemical difference in these two subsites
is available from transport systems for neutral aand
p-amino acids. A strong transporti nhibition of the
hepatocyte system by 3-aminoglutarate shows that an
a,a relation between the amino group and eitheor f the
carboxylate groups of the anionic amino acid is not
required. The above anomaly in stereoselectivity is
compared with a corresponding one, applying to the
reactions of aspartic acid and asparagine, versus glutamic
acid and glutamine, with System L for neutral
amino acid transport in the Ehrlich cell. A weak pHdependent
inhibition of the uptake of anionic amino
acids by cysteine can be associated with its unique
mode of conversion to an anionic species
Fetal hepatic and umbilical uptakes of glucogenic substrates during a glucagon-somatostatin infusion
Nutrition Education in U.S. Medical Schools: Latest Update of a National Survey
PURPOSE: To quantify the number of required hours of nutrition education at U.S. medical schools and the types of courses in which the instruction was offered, and to compare these results with results from previous surveys. METHOD: The authors distributed to all 127 accredited U.S. medical schools (that were matriculating students at the time of this study) a two-page online survey devised by the Nutrition in Medicine Project at the University of North Carolina at Chapel Hill. From August 2008 through July 2009, the authors asked their contacts, most of whom were nutrition educators, to report the nutrition contact hours that were required for their medical students and whether those actual hours of nutrition education occurred in a designated nutrition course, within another course, or during clinical rotations. RESULTS: Respondents from 109 (86%) of the targeted medical schools completed some part of the survey. Most schools (103/109) required some form of nutrition education. Of the 105 schools answering questions about courses and contact hours, only 26 (25%) required a dedicated nutrition course; in 2004, 32 (30%) of 106 schools did. Overall, medical students received 19.6 contact hours of nutrition instruction during their medical school careers (range: 0–70 hours); the average in 2004 was 22.3 hours. Only 28 (27%) of the 105 schools met the minimum 25 required hours set by the National Academy of Sciences; in 2004, 40 (38%) of 104 schools did so. CONCLUSIONS: The amount of nutrition education that medical students receive continues to be inadequate
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