FASEB J. 2012 Aug;26(8):3140-7. doi: 10.1096/fj.11-198515. Epub 2012 Apr 24. MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism. Peng H, Hamanaka RB, Katsnelson J, Hao LL, Yang W, Chandel NS, Lavker RM. Corneal epithelium relies on abundant glycogen stores as its primary energy source. MicroRNA-31 (miR-31), a corneal epithelial-preferred miRNA, negatively regulates factor inhibiting hypoxia-inducible factor-1 (FIH-1). Since HIF-1α is involved in anaerobic energy production, we investigated the role that miR-31 and FIH-1 play in regulating corneal epithelial glycogen. We used antagomirs (antago) to reduce the level of miR-31 in primary human corneal epithelial keratinocytes (HCEKs), and a miR-31- resistant FIH-1 to increase FIH-1 levels. Antago-31 raised FIH-1 levels and significantly reduced glycogen stores in HCEKs compared to irrelevant-antago treatment. Similarly, HCEKs retrovirally transduced with a miR-31-resistant FIH-1 had markedly reduced glycogen levels compared with empty vector controls. In addition, we observed no change in a HIF-1α reporter or known genes downstream of HIF-1α indicating that the action of FIH-1 and miR-31 on glycogen is HIF-1α-independent. An enzyme-dead FIH-1 mutation failed to restore glycogen stores, indicating that FIH-1 negatively regulates glycogen in a hydroxylase-independent manner. FIH-1 overexpression in HCEKs decreased AKT signaling, activated GSK-3β, and inactivated glycogen synthase. Treatment of FIH-1-transduced HCEKs with either a myristolated Akt or a GSK-3β inhibitor restored glycogen stores, confirming the direct involvement of Akt/GSK-3β signaling. Silencing FIH-1 in HCEKs reversed the observed changes in Akt-signaling. Glycogen regulation in a HIF-1α- independent manner is a novel function for FIH-1 and provides new insight into how the corneal epithelium regulates its energy requirements.
f*t
3 楼
开始看了,不错。现在有高清版本了。
a*k
4 楼
这个很奇葩。。
24. glycogen energy
【在 r**o 的大作中提到】 : FASEB J. 2012 Aug;26(8):3140-7. doi: 10.1096/fj.11-198515. Epub 2012 Apr 24. : MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen : metabolism. : Peng H, Hamanaka RB, Katsnelson J, Hao LL, Yang W, Chandel NS, Lavker RM. : Corneal epithelium relies on abundant glycogen stores as its primary energy : source. MicroRNA-31 (miR-31), a corneal epithelial-preferred miRNA, : negatively regulates factor inhibiting hypoxia-inducible factor-1 (FIH-1). : Since HIF-1α is involved in anaerobic energy production, we investigated : the role that miR-31 and FIH-1 play in regulating corneal epithelial : glycogen. We used antagomirs (antago) to reduce the level of miR-31 in
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24. glycogen energy
【在 r**o 的大作中提到】 : FASEB J. 2012 Aug;26(8):3140-7. doi: 10.1096/fj.11-198515. Epub 2012 Apr 24. : MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen : metabolism. : Peng H, Hamanaka RB, Katsnelson J, Hao LL, Yang W, Chandel NS, Lavker RM. : Corneal epithelium relies on abundant glycogen stores as its primary energy : source. MicroRNA-31 (miR-31), a corneal epithelial-preferred miRNA, : negatively regulates factor inhibiting hypoxia-inducible factor-1 (FIH-1). : Since HIF-1α is involved in anaerobic energy production, we investigated : the role that miR-31 and FIH-1 play in regulating corneal epithelial : glycogen. We used antagomirs (antago) to reduce the level of miR-31 in
【在 r**o 的大作中提到】 : FASEB J. 2012 Aug;26(8):3140-7. doi: 10.1096/fj.11-198515. Epub 2012 Apr 24. : MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen : metabolism. : Peng H, Hamanaka RB, Katsnelson J, Hao LL, Yang W, Chandel NS, Lavker RM. : Corneal epithelium relies on abundant glycogen stores as its primary energy : source. MicroRNA-31 (miR-31), a corneal epithelial-preferred miRNA, : negatively regulates factor inhibiting hypoxia-inducible factor-1 (FIH-1). : Since HIF-1α is involved in anaerobic energy production, we investigated : the role that miR-31 and FIH-1 play in regulating corneal epithelial : glycogen. We used antagomirs (antago) to reduce the level of miR-31 in