Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: EC:2.7.7.49 (
reverse transcriptase
)
31,746
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The non-essential amino acid L-serine was shown to be required to support the survival of rat cerebellar Purkinje neurons because of lack of the expression of the L-serine biosynthesis enzyme
3-phosphoglycerate dehydrogenase
in them. In the present study, we investigated L-[(3)H]serine uptake in primary cultures of neurons and astrocytes from the rat telencephalon. In both neurons and astrocytes, L-[(3)H]serine uptake was dependent on temperature and Na(+) ions, and exhibited a single component of high-affinity uptake sites (K(m)=15.0 and 17.2 micro M for neurons and astrocytes, respectively). Kinetic analysis of L-[(3)H]serine uptake also revealed that the uptake into neurons was faster than that into astrocytes. The selectivity of inhibition by amino acids of the L-[(3)H]serine uptake resembled that of the system ASC transporters ASCT1 and ASCT2. Neutral amino acids L-alanine, L-serine, L-cysteine, and L-threonine strongly inhibited the uptake by both cell types. Furthermore, in astrocytes, but not in neurons, L-valine and L-proline also inhibited L-[(3)H]serine uptake. Neither alpha-methyl aminoisobutyric acid (a system A-specific substrate) nor 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (a system L-specific substrate) inhibited the uptake of L-[(3)H]serine in both neurons and astrocytes. Expression of ASCT transporters in both neurons and astrocytes was examined by use of
reverse transcriptase
polymerase chain reaction and immunoblot analysis. Whereas transcripts (mRNAs) of both ASCT1 and ASCT2 transporters were detected in astrocytes, only the mRNA of the former subtype was detected in neurons. Immunoblot analysis confirmed the presence of ASCT1 in both neurons and astrocytes. These findings indicate that neurons accumulate a high level of L-serine by using a Na(+)-dependent, high-affinity transport system, operating predominantly through the ASCT1 transporter subtype.
...
PMID:Characterization of rapid and high-affinity uptake of L-serine in neurons and astrocytes in primary culture. 1288 9
Tumors have exceptionally high demands for energy and anabolism because of their rapid growth. The de novo serine synthesis pathway initiated by
phosphoglycerate dehydrogenase
(
PHGDH
) has been recognized as a hallmark of metabolic adaption in carcinogenesis. The oncogenic role and prognostic value of
PHGDH
have been investigated in multiple cancer types, including breast cancer, melanoma, cervical cancer, and colon cancer. Due to the importance of
PHGDH
in cancer, we attempted to determine the clinical significance of
PHGDH
in 319 patients with non-small cell lung cancer (NSCLC). We evaluated the mRNA and protein expression levels of
PHGDH
gene, using quantitative
reverse transcriptase
polymerase chain reaction and tissue array-based immunohistochemistry, respectively. Significantly increased
PHGDH
expression in mRNA and protein levels was identified in tumor tissues versus matched adjacent nontumor tissues. More interestingly, immunohistochemical expression of
PHGDH
was significantly associated with lymph node metastasis (P=.021) and TNM stage (P=.016). Kaplan-Meier survival analysis indicated that NSCLC patients with low levels of
PHGDH
outperformed patients with high levels of
PHGDH
regarding 5-year overall survival. Significantly longer survival in the former suggested the prognostic implication of
PHGDH
in NSCLC. Multivariate survival analysis using Cox regression model demonstrated that high
PHGDH
levels and advanced TNM stage (III+IV) were independent predictors of prognosis in NSCLC. Moreover, bioinformatics analysis confirmed the increase in
PHGDH
transcripts (data from The Cancer Genome Atlas) and its prognostic value (Kaplan-Meier plotter) in NSCLC. In conclusion, this study suggested the clinical implication of
PHGDH
in NSCLC.
PHGDH
may be a promising therapeutic target in NSCLC.
...
PMID:High Expression of PHGDH Predicts Poor Prognosis in Non-Small Cell Lung Cancer. 2791 94
