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Science Forum Index » Life Extension Forum » High sugar promotes ESC proliferation via PGE2...
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| Taka... |
 Posted: Sat Jun 07, 2008 1:59 am |
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Stem Cells. 2008 Mar;26(3):745-55. Epub 2007 Dec 20.
High-glucose-induced prostaglandin E(2) and peroxisome proliferator-
activated receptor delta promote mouse embryonic stem cell
proliferation.
Kim YH, Han HJ.
Department of Veterinary Physiology, College of Veterinary Medicine,
Chonnam National University, Gwangju 500-757, Korea.
Peroxisome proliferator-activated receptor is a nuclear receptor that
has been implicated in blastocyst implantation, cell cycle, and
pathogenesis of diabetes. However, the signal cascades underlying this
effect are largely unknown in embryo stem cells. This study examined
whether or not there is an association between the reactive oxygen
species-mediated prostaglandin E(2) (PGE(2))/peroxisome proliferator-
activated receptor (PPAR) delta and the growth response to high
glucose levels in mouse ESCs. A high concentration of glucose (25 mM)
significantly increased the level of [3H]thymidine incorporation, the
level of 5-bromo-2'-deoxyuridine incorporation, and the number of
cells. Moreover, 25 mM glucose increased the intracellular reactive
oxygen species, phosphorylation of the cytosolic phospholipase A(2)
(cPLA(2)), and the release of [3H]arachidonic acid ([3H]AA). In
addition, 25 mM glucose also increased the level of cyclooxygenase-2
(COX-2) protein expression, which stimulated the synthesis of PGE(2).
Subsequently, high glucose-induced PGE(2) stimulated PPARdelta
expression directly or through Akt phosphorylation indirectly through
the E type prostaglandin receptor receptors. The PPARdelta antagonist
inhibited the 25 mM glucose-induced DNA synthesis. Moreover,
transfection with a pool of PPARdelta-specific small interfering RNA
inhibited the 25 mM glucose-induced DNA synthesis and G1/S phase
progression. Twenty-five millimolar glucose also increased the level
of the cell cycle regulatory proteins (cyclin E/cyclin-dependent
kinase [CDK] 2 and cyclin D1/CDK 4) and decreased p21(WAF1/Cip1) and
p27(Kip1), which were blocked by the inhibition of the cPLA(2), COX-2,
or PPARdelta pathways. In conclusion, high glucose promotes mouse ESC
growth in part through the cPLA(2)-mediated PGE(2) synthesis and in
part through PPARdelta pathways.
PMID: 18096720 |
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