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PMID:20356836

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Citation

Jensen, PJ, Gunter, LB and Carayannopoulos, MO (2010) Akt2 modulates glucose availability and downstream apoptotic pathways during development. J. Biol. Chem. 285:17673-80

Abstract

Glucose is the primary energy substrate for eukaryotic cells and the predominant substrate for the brain. Studies suggest that glucose serves an additional role in the regulation of cellular functions, including viability. Zebrafish is a tractable system for defining the cellular and molecular mechanisms perturbed by impaired glucose transport and metabolism. Previously, we demonstrated a critical role for the facilitative glucose transporter, Glut1, in the regulation of embryonic brain development. In this study, we aim to identify mediators in this Glut1-sensitive process by investigating the role of the antiapoptotic kinase, Akt2. Results show that abrogating expression of akt2 causes a phenotype strikingly similar to that observed when glut1 expression is inhibited. akt2-deficient embryos exhibit increased neuronal apoptosis, impaired glucose uptake, and death by 72 h postfertilization. Similar to what was observed in the glut1 morphants, inhibiting the expression of the proapoptotic protein, bad, in the context of impaired akt2 expression results in the inhibition of apoptosis and rescue of the morphant embryos. Intriguingly, overexpression of glut1 in the akt2 morphants was also able to rescue these embryos. Quantitative reverse transcription-PCR analysis revealed decreased glut1 transcript expression in akt2 morphant embryos. Taken together, these data suggest that Akt2 modulates glucose availability by regulating Glut1 expression at the transcript level. These data support a role for akt2 in an integrative pathway directly linking glucose, Glut1 expression, and activation of apoptosis and demonstrate the dependence of akt2 on glucose availability for the maintenance of cellular viability, particularly in the central nervous system.

Links

PubMed PMC2878531 Online version:10.1074/jbc.M109.079343

Keywords

Animals; Apoptosis; Brain/embryology; Brain/metabolism; Cell Survival; Central Nervous System/metabolism; Gene Expression Regulation, Developmental; Glucose/metabolism; Glucose Transporter Type 1/metabolism; Microscopy, Fluorescence/methods; Models, Biological; Phenotype; Proto-Oncogene Proteins c-akt/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Zebrafish

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A7MCM4

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060608-1,ZFIN:ZDB-MRPHLNO-100621-7

P

Seeded From UniProt

complete

DANRE:Q285P3

involved_in

GO:0046323: glucose import

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060608-3

P

Seeded From UniProt

complete

DANRE:Q4V925

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060608-1,ZFIN:ZDB-MRPHLNO-100621-7

P

Seeded From UniProt

complete

DANRE:Q8UUX0

involved_in

GO:0046326: positive regulation of glucose import

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100621-7

P

Seeded From UniProt

complete

DANRE:Q8UUX0

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100621-7

P

Seeded From UniProt

complete

DANRE:Q9I9N2

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060608-1,ZFIN:ZDB-MRPHLNO-100621-7

P

Seeded From UniProt

complete


See also

References

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