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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 294 - 301 (8page)
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Under hypoxia, mouse embryonic stem cells (mESCs)lose their self-renewal activity and display an early differentiated morphology mediated by the hypoxia-inducible factor-1α (HIF-1α). Previous studies have demonstrated that PKC-δ is activated by hypoxia and increases the protein stability and transcriptional activity of HIF-1α in human cancer cells. Furthermore, activation of PKC-δ mediates cardiac differentiation of ESCs and hematopoietic stem cells. However, the role of PKC-δ in hypoxia-induced early differentiation of mESCs remains largely unknown. Here, we show the inhibition of PKC-δ activity prevents the early differentiation of mESCs under hypoxia using PKC-δ inhibitors,GF 109203X and rottlerin. Reduction of PKC-δactivity under hypoxia effectively decreased HIF-1αprotein levels and substantially recovered the expression of LIF-specific receptor (LIFR) and phosphorylated-STAT3 in mESCs. Furthermore, PKC-δ 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-δ inhibitors block the early differentiation of mESCs via destabilization of HIF-1α under hypoxia.
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참고문헌 (24)
참고문헌 신청
Bae SH / 2004 / Sumoylation increases HIF-1alpha stability and its transcriptional activity / Biochem Biophys Res Commun 324 : 394 ~ 400
Baek SH / 2001 / Role of protein kinase Cdelta in transmitting hypoxia signal to HSF and HIF-1 / J Cell Physiol 188 : 223 ~ 235
Berra E / 2003 / HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia / EMBO J 22 : 4082 ~ 4090
Bhattacharjee A / 2006 / Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with protein kinase C delta and tyrosine-phosphorylated Stat3
Bost F / 2002 / Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage / Biochem J 361 : 621 ~ 627
Baek SH / 2001 / Role of protein kinase Cdelta in transmitting hypoxia signal to HSF and HIF-1 / J Cell Physiol 188 : 223 ~ 235
Berra E / 2003 / HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia / EMBO J 22 : 4082 ~ 4090
Bhattacharjee A / 2006 / Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with protein kinase C delta and tyrosine-phosphorylated Stat3
Bost F / 2002 / Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage / Biochem J 361 : 621 ~ 627
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