Abstract
High glucose-induced protein synthesis in the glomerular epithelial cell (GEC) is partly dependent on reduction in phosphorylation of AMP-activated protein kinase (AMPK). We evaluated the effect of resveratrol, a phytophenol known to stimulate AMPK, on protein synthesis. Resveratrol completely inhibited high glucose stimulation of protein synthesis and synthesis of fibronectin, an important matrix protein, at 3 days. Resveratrol dose-dependently increased AMPK phosphorylation and abolished high glucose-induced reduction in its phosphorylation. We examined the effect of resveratrol on critical steps in mRNA translation, a critical event in protein synthesis. Resveratrol inhibited high glucose-induced changes in association of eIF4E with eIF4G, phosphorylation of eIF4E, eEF2, eEF2 kinase and, p70S6 kinase, indicating that it affects important events in both initiation and elongation phases of mRNA translation. Upstream regulators of AMPK in high glucose-treated GEC were explored. High glucose augmented acetylation of LKB1, the upstream kinase for AMPK, and inhibited its activity. Resveratrol prevented acetylation of LKB1 and restored its activity in high glucose-treated cells; this action did not appear to depend on SIRT1, a class III histone deacetylase. Our data show that resveratrol ameliorates protein synthesis by regulating the LKB1-AMPK axis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 65-70 |
| Number of pages | 6 |
| Journal | Cellular Signalling |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2010 |
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Keywords
- AMP-activated protein kinase
- Diabetic nephropathy
- LKB1
- Protein synthesis
ASJC Scopus subject areas
- Cell Biology
Cite this
Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells. / Lee, Myung Ja; Feliers, Denis; Sataranatarajan, Kavithalakshmi; Mariappan, Meenalakshmi M.; Li, Manli; Barnes, Jeffrey L.; Ghosh-choudhury, Goutam; Kasinath, Balakuntalam S.
In: Cellular Signalling, Vol. 22, No. 1, 01.2010, p. 65-70.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells
AU - Lee, Myung Ja
AU - Feliers, Denis
AU - Sataranatarajan, Kavithalakshmi
AU - Mariappan, Meenalakshmi M.
AU - Li, Manli
AU - Barnes, Jeffrey L.
AU - Ghosh-choudhury, Goutam
AU - Kasinath, Balakuntalam S
PY - 2010/1
Y1 - 2010/1
N2 - High glucose-induced protein synthesis in the glomerular epithelial cell (GEC) is partly dependent on reduction in phosphorylation of AMP-activated protein kinase (AMPK). We evaluated the effect of resveratrol, a phytophenol known to stimulate AMPK, on protein synthesis. Resveratrol completely inhibited high glucose stimulation of protein synthesis and synthesis of fibronectin, an important matrix protein, at 3 days. Resveratrol dose-dependently increased AMPK phosphorylation and abolished high glucose-induced reduction in its phosphorylation. We examined the effect of resveratrol on critical steps in mRNA translation, a critical event in protein synthesis. Resveratrol inhibited high glucose-induced changes in association of eIF4E with eIF4G, phosphorylation of eIF4E, eEF2, eEF2 kinase and, p70S6 kinase, indicating that it affects important events in both initiation and elongation phases of mRNA translation. Upstream regulators of AMPK in high glucose-treated GEC were explored. High glucose augmented acetylation of LKB1, the upstream kinase for AMPK, and inhibited its activity. Resveratrol prevented acetylation of LKB1 and restored its activity in high glucose-treated cells; this action did not appear to depend on SIRT1, a class III histone deacetylase. Our data show that resveratrol ameliorates protein synthesis by regulating the LKB1-AMPK axis.
AB - High glucose-induced protein synthesis in the glomerular epithelial cell (GEC) is partly dependent on reduction in phosphorylation of AMP-activated protein kinase (AMPK). We evaluated the effect of resveratrol, a phytophenol known to stimulate AMPK, on protein synthesis. Resveratrol completely inhibited high glucose stimulation of protein synthesis and synthesis of fibronectin, an important matrix protein, at 3 days. Resveratrol dose-dependently increased AMPK phosphorylation and abolished high glucose-induced reduction in its phosphorylation. We examined the effect of resveratrol on critical steps in mRNA translation, a critical event in protein synthesis. Resveratrol inhibited high glucose-induced changes in association of eIF4E with eIF4G, phosphorylation of eIF4E, eEF2, eEF2 kinase and, p70S6 kinase, indicating that it affects important events in both initiation and elongation phases of mRNA translation. Upstream regulators of AMPK in high glucose-treated GEC were explored. High glucose augmented acetylation of LKB1, the upstream kinase for AMPK, and inhibited its activity. Resveratrol prevented acetylation of LKB1 and restored its activity in high glucose-treated cells; this action did not appear to depend on SIRT1, a class III histone deacetylase. Our data show that resveratrol ameliorates protein synthesis by regulating the LKB1-AMPK axis.
KW - AMP-activated protein kinase
KW - Diabetic nephropathy
KW - LKB1
KW - Protein synthesis
UR - http://www.scopus.com/inward/record.url?scp=70350043289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350043289&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2009.09.011
DO - 10.1016/j.cellsig.2009.09.011
M3 - Article
C2 - 19765649
AN - SCOPUS:70350043289
VL - 22
SP - 65
EP - 70
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 1
ER -