Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

HIF and reactive oxygen species regulate oxidative phosphorylation in cancer

E Hervouet, A Cizkova, J Demont, A Vojtiskova, P Pecina, Hal NL Franssen-van, J Keijer, H Simonnet, R Ivanek, S Kmoch, C Godinot, J Houstek

. 2008 ; 29 (8) : 1528-1537.

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc13026813

Grantová podpora
NR8069 MZ0 CEP - Centrální evidence projektů

A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-alpha) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-alpha synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-alpha subunit by CoCl(2) decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H(2)O(2.) Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl(2) significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc13026813
003      
CZ-PrNML
005      
20130830151854.0
007      
ta
008      
130815s2008 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/carcin/bgn125 $2 doi
035    __
$a (PubMed)18515279
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Hervouet, Eric $u Centre de Genetique Moleculaire et Cellulaire, UMR 5534, Centre National de la Recherche Scientifique, Claude Bernard University of Lyon 1, 43 Boulevard du onze novembre, 69622 Villeurbanne, Cedex, France.
245    10
$a HIF and reactive oxygen species regulate oxidative phosphorylation in cancer / $c E Hervouet, A Cizkova, J Demont, A Vojtiskova, P Pecina, Hal NL Franssen-van, J Keijer, H Simonnet, R Ivanek, S Kmoch, C Godinot, J Houstek
520    9_
$a A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-alpha) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-alpha synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-alpha subunit by CoCl(2) decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H(2)O(2.) Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl(2) significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production.
590    __
$a bohemika - dle Pubmed
650    12
$a receptory aromatických uhlovodíků - jaderný translokátor $x genetika $x metabolismus $7 D051784
650    02
$a transportní proteiny $x genetika $x metabolismus $7 D002352
650    02
$a kobalt $x farmakologie $7 D003035
650    02
$a deferoxamin $x farmakologie $7 D003676
650    02
$a glykolýza $x genetika $7 D006019
650    02
$a homeostáza $7 D006706
650    02
$a lidé $7 D006801
650    02
$a peroxid vodíku $x farmakologie $7 D006861
650    12
$a faktor 1 indukovatelný hypoxií - podjednotka alfa $x genetika $x metabolismus $7 D051795
650    02
$a nádory $x genetika $7 D009369
650    02
$a sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů $7 D020411
650    12
$a oxidativní fosforylace $7 D010085
650    12
$a reaktivní formy kyslíku $x metabolismus $7 D017382
650    02
$a respirační vzplanutí $x fyziologie $x účinky léků $7 D016897
650    02
$a polymerázová řetězová reakce s reverzní transkripcí $7 D020133
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Čížková, Alena, $d 1981- $7 jo2010566488 $u Institute of Physiology, Academy of Sciences of the Czech Republic, Czech Republic; Institute of Inherited Metabolic Disorders, Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Demont, Jocelyne
700    1_
$a Vojtíšková, Alena $7 _AN035246 $u Institute of Physiology, Academy of Sciences of the Czech Republic, Czech Republic
700    1_
$a Pecina, Petr $7 xx0141218 $u Institute of Physiology, Academy of Sciences of the Czech Republic, Czech Republic
700    1_
$a Franssen-van Hal, Nicole L.W.
700    1_
$a Keijer, Jaap
700    1_
$a Simonnet, Helene
700    1_
$a Ivánek, Robert $7 xx0118825 $u Institute of Inherited Metabolic Disorders, Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Czech Republic
700    1_
$a Kmoch, Stanislav, $d 1963- $7 xx0056529 $u Institute of Inherited Metabolic Disorders, Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Godinot, Catherine
700    1_
$a Houštěk, Josef, $7 xx0030591 $u Institute of Physiology, Academy of Sciences of the Czech Republic, Czech Republic $d 1947-
773    0_
$t Carcinogenesis $g Roč. 29, č. 8 (2008), s. 1528-1537 $p Carcinogenesis $x 0143-3334 $w MED00001050
910    __
$a ABA008 $b B 2192 $y 3 $z 0
990    __
$a 20130815091345 $b ABA008
991    __
$a 20130830152338 $b ABA008
999    __
$a ok $b bmc $g 990686 $s 825235
BAS    __
$a 3
BMC    __
$x MED00001050 $i 0143-3334 $a 2008 $b 29 $c 8 $d 1528-1537 $m Carcinogenesis $n Carcinogenesis
GRA    __
$a NR8069 $p MZ0
LZP    __
$a NLK 2013-08/lpbo

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace