PMID- 21970364
OWN - NLM
STAT- MEDLINE
DCOM- 20120214
LR  - 20161125
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 441
IP  - 2
DP  - 2012 Jan 15
TI  - Hypoxia-inducible factor-1 (HIF-1) promotes LDL and VLDL uptake through inducing 
      VLDLR under hypoxia.
PG  - 675-83
LID - 10.1042/BJ20111377 [doi]
AB  - Metabolism under hypoxia is significantly different from that under normoxia. It 
      has been well elucidated that HIF-1 (hypoxia-inducible factor-1) plays a central 
      role in regulating glucose metabolism under hypoxia; however, the role of HIF-1 
      in lipid metabolism has not yet been well addressed. In the present study we 
      demonstrate that HIF-1 promotes LDL (low-density lipoprotein) and VLDL (very-LDL) 
      uptake through regulation of VLDLR (VLDL receptor) gene expression under hypoxia. 
      Increased VLDLR mRNA and protein levels were observed under hypoxic or DFO 
      (deferoxamine mesylate salt) treatment in MCF7, HepG2 and HeLa cells. Using 
      dual-luciferase reporter and ChIP (chromatin immunoprecipitation) assays we 
      confirmed a functional HRE (hypoxia-response element) which is localized at +405 
      in exon 1 of the VLDLR gene. Knockdown of HIF1A (the alpha subunit of HIF-1) and 
      VLDLR, but not HIF2A (the alpha subunit of HIF-2), attenuated hypoxia-induced lipid 
      accumulation through affecting LDL and VLDL uptake. Additionally we also observed 
      a correlation between HIF-1 activity and VLDLR expression in hepatocellular 
      carcinoma specimens. The results of the present study suggest that HIF-1-mediated 
      VLDLR induction influences intracellular lipid accumulation through regulating 
      LDL and VLDL uptake under hypoxia.
FAU - Shen, Guo-Min
AU  - Shen GM
AD  - Department of Biochemistry and Molecular Biology and National Laboratory of 
      Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
FAU - Zhao, Ying-Ze
AU  - Zhao YZ
FAU - Chen, Ming-Tai
AU  - Chen MT
FAU - Zhang, Feng-Lin
AU  - Zhang FL
FAU - Liu, Xiao-Ling
AU  - Liu XL
FAU - Wang, Yi
AU  - Wang Y
FAU - Liu, Chang-Zheng
AU  - Liu CZ
FAU - Yu, Jia
AU  - Yu J
FAU - Zhang, Jun-Wu
AU  - Zhang JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Lipoproteins, VLDL)
RN  - 0 (Receptors, LDL)
RN  - 0 (VLDL receptor)
SB  - IM
MH  - Cell Line, Tumor
MH  - Humans
MH  - Hypoxia/*metabolism
MH  - Hypoxia-Inducible Factor 1/*physiology
MH  - Lipoproteins, LDL/*metabolism
MH  - Lipoproteins, VLDL/*metabolism
MH  - Receptors, LDL/*biosynthesis
EDAT- 2011/10/06 06:00
MHDA- 2012/02/15 06:00
CRDT- 2011/10/06 06:00
PHST- 2011/10/06 06:00 [entrez]
PHST- 2011/10/06 06:00 [pubmed]
PHST- 2012/02/15 06:00 [medline]
AID - BJ20111377 [pii]
AID - 10.1042/BJ20111377 [doi]
PST - ppublish
SO  - Biochem J. 2012 Jan 15;441(2):675-83. doi: 10.1042/BJ20111377.