Journal
EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 42, Issue 4, Pages 294-301Publisher
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2010.42.4.028
Keywords
anoxia; embryonic stem cells; hypoxia-inducible factor 1, alpha subunit; protein kinase C-delta; rottlerin
Funding
- Creative Research Initiatives (NeuroVascular Coordination Research Center) of MOST/KOSEF, Korea [R16-2004-001-01001-0, 2009]
Ask authors/readers for more resources
Under hypoxia, mouse embryonic stem cells (mESCs) lose their self-renewal activity and display an early differentiated morphology mediated by the hypoxia-inducible factor-1 alpha (HIF-1 alpha). Previous studies have demonstrated that PKC-delta is activated by hypoxia and increases the protein stability and transcriptional activity of HIF-1 alpha in human cancer cells. Furthermore, activation of PKC-delta mediates cardiac differentiation of ESCs and hematopoietic stem cells. However, the role of PKC-delta in hypoxia-induced early differentiation of mESCs remains largely unknown. Here, we show the inhibition of PKC-delta activity prevents the early differentiation of mESCs under hypoxia using PKC-delta inhibitors, GF 109203X and rottlerin. Reduction of PKC-delta activity under hypoxia effectively decreased HIF-1 alpha protein levels and substantially recovered the expression of LIF-specific receptor (LIFR) and phosphorylated-STAT3 in mESCs. Furthermore, PKC-delta inhibitors aid to sustain the expression of self-renewal markers and suppress the expression of early differentiation markers in mESCs under hypoxia. Taken together, these results suggest that PKC-delta inhibitors block the early differentiation of mESCs via destabilization of HIF-1 alpha under hypoxia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available