PMID- 26608793
OWN - NLM
STAT- MEDLINE
DCOM- 20161019
LR  - 20161230
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 7
IP  - 1
DP  - 2016 Jan
TI  - Hydroxytyrosol decreases the oxidative and nitrosative stress levels and promotes 
      angiogenesis through HIF-1 independent mechanisms in renal hypoxic cells.
PG  - 540-8
LID - 10.1039/c5fo00928f [doi]
AB  - In the kidney, tissue oxygen tension is comparatively low and this renders this 
      organ more prone to hypoxic injury. In fact, hypoxia has a central role in the 
      development and progression of renal disease. The recovery from this situation is 
      dependent on the degree to which sublethally damaged cells restore normal 
      function. The master regulator of the hypoxic response is hypoxia-inducible 
      factor-1 (HIF-1). HIF-1 activity depends on the HIF-1alpha subunit level which is 
      regulated by oxygen, nitric oxide (NO), reactive oxygen species and mTOR. Given 
      the antioxidant and antinitrosative properties ascribed to hydroxytyrosol (HT), 
      this study evaluates the impact of this olive oil polyphenol on the response to 
      hypoxia in kidney cells. For this purpose, the human embryonic kidney HEK293T 
      cell line was treated with HT and cultured under sublethal hypoxic conditions. 
      Our results demonstrate that HT treatment decreases both, post-hypoxic reactive 
      oxygen species and NO levels and, consequently, HIF-1alpha accumulation. However, HT 
      does not affect mTOR activation or the factor inhibiting HIF level but promotes 
      the expression of angiogenic proteins, suggesting that HT activates an adaptive 
      response to hypoxia in a HIF-1alpha-independent pathway. In fact, this effect could 
      be ascribed to the up-regulation of estrogen-related receptor alpha. In conclusion, 
      our results suggest that in renal hypoxia, HT treatment might act as an effective 
      preventive therapeutic approach to decrease stress and to improve the adaptive 
      response to this pathological situation.
FAU - Martinez-Lara, Esther
AU  - Martinez-Lara E
AD  - Department of Experimental Biology, University of Jaen, Paraje Las Lagunillas 
      s/n, 23071-Jaen, Spain. esiles@ujaen.es.
FAU - Pena, Ana
AU  - Pena A
AD  - Department of Experimental Biology, University of Jaen, Paraje Las Lagunillas 
      s/n, 23071-Jaen, Spain. esiles@ujaen.es.
FAU - Calahorra, Jesus
AU  - Calahorra J
AD  - Department of Experimental Biology, University of Jaen, Paraje Las Lagunillas 
      s/n, 23071-Jaen, Spain. esiles@ujaen.es.
FAU - Canuelo, Ana
AU  - Canuelo A
AD  - Department of Experimental Biology, University of Jaen, Paraje Las Lagunillas 
      s/n, 23071-Jaen, Spain. esiles@ujaen.es.
FAU - Siles, Eva
AU  - Siles E
AD  - Department of Experimental Biology, University of Jaen, Paraje Las Lagunillas 
      s/n, 23071-Jaen, Spain. esiles@ujaen.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Olive Oil)
RN  - 10597-60-1 (3,4-dihydroxyphenylethanol)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
SB  - IM
MH  - Cell Line, Tumor
MH  - DNA Damage/drug effects
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Hydrogen Peroxide
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Leukocytes, Mononuclear/*drug effects
MH  - Neovascularization, Physiologic/*drug effects
MH  - Olive Oil/chemistry
MH  - Oxidative Stress/*drug effects
MH  - Phenylethyl Alcohol/*analogs & derivatives/chemistry/pharmacology
EDAT- 2015/11/27 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/11/27 06:00
PHST- 2015/11/27 06:00 [entrez]
PHST- 2015/11/27 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - 10.1039/c5fo00928f [doi]
PST - ppublish
SO  - Food Funct. 2016 Jan;7(1):540-8. doi: 10.1039/c5fo00928f.