Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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PKC-$\delta$ inhibitors sustain self-renewal of mouse embryonic stem cells under hypoxia in vitro

Lee, Hyo-Jong;Jeong, Chul-Ho;Cha, Jong-Ho;Kim, Kyu-Won

  • Published : 20100400
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Abstract

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.

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References

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