-
Something wrong with this record ?
Intracellular accumulation of bilirubin as a defense mechanism against increased oxidative stress
Jaroslav Zelenka, Lucie Muchova, Miroslava Zelenkova, Katerina Vanova, Hendrik J. Vreman, Ronald J. Wong, Libor Vitek
Language English Country France
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT11327
MZ0
CEP Register
- MeSH
- Enzyme Activation drug effects MeSH
- Antioxidants metabolism MeSH
- Arsenites pharmacology MeSH
- Bilirubin administration & dosage analogs & derivatives metabolism MeSH
- Hep G2 Cells MeSH
- Heme analysis MeSH
- Heme Oxygenase-1 metabolism MeSH
- Hyperbilirubinemia metabolism MeSH
- Rats MeSH
- Humans MeSH
- Lipopolysaccharides administration & dosage MeSH
- Methemalbumin pharmacology MeSH
- Oxidative Stress drug effects MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Wistar MeSH
- Sodium Compounds pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Antioxidant, anti-inflammatory and anti-atherogenic effects have been associated with elevations of unconjugated bilirubin (UCB) in serum and with the induction of heme oxygenase-1 (HO-1), the rate-limiting enzyme in UCB synthesis. The aim of this study was to investigate the intracellular metabolism and antioxidant properties of UCB in human hepatoblastoma HepG2 cells and tissues of Wistar rats exposed to oxidative stressors and lipopolysaccharide (LPS), respectively. Intracellular UCB concentrations in HepG2 cells correlated with its levels in culture media (p < 0.001) and diminished lipid peroxidation in a dose-dependent manner (p < 0.001). Moreover, induction of HO-1 with sodium arsenite led to 2.4-fold (p = 0.01) accumulation of intracellular UCB over basal level while sodium azide-derived oxidative stress resulted in a 60% drop (p < 0.001). This decrease was ameliorated by UCB elevation in media or by simultaneous induction of HO-1. In addition, hyperbilirubinemia and liver HO-1 induction in LPS-treated rats resulted in a 2-fold accumulation of tissue UCB (p = 0.01) associated with enhanced protection against lipid peroxidation (p = 0.02). In conclusion, hyperbilirubinemia and HO-1 induction associated with inflammation and oxidative stress increase intracellular concentrations of UCB, thus enhancing the protection of cellular lipids against peroxidation. Therefore, the previously reported protective effects of hyperbilirubinemia and HO-1 induction are at least in part due to intracellular accumulation of UCB.
4th Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Czech Republic
Department of Pediatrics Stanford University School of Medicine Stanford CA USA
Institute of Physiology Academy of Sciences Dept 75 Prague Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc13000815
- 003
- CZ-PrNML
- 005
- 20150107121020.0
- 007
- ta
- 008
- 130108s2012 fr f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.biochi.2012.04.026 $2 doi
- 035 __
- $a (PubMed)22580386
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a fr
- 100 1_
- $a Zelenka, Jaroslav $u Institute of Physiology, Academy of Sciences, Dept. 75, Prague, Czech Republic. jar.zelenka@gmail.com
- 245 10
- $a Intracellular accumulation of bilirubin as a defense mechanism against increased oxidative stress / $c Jaroslav Zelenka, Lucie Muchova, Miroslava Zelenkova, Katerina Vanova, Hendrik J. Vreman, Ronald J. Wong, Libor Vitek
- 520 9_
- $a Antioxidant, anti-inflammatory and anti-atherogenic effects have been associated with elevations of unconjugated bilirubin (UCB) in serum and with the induction of heme oxygenase-1 (HO-1), the rate-limiting enzyme in UCB synthesis. The aim of this study was to investigate the intracellular metabolism and antioxidant properties of UCB in human hepatoblastoma HepG2 cells and tissues of Wistar rats exposed to oxidative stressors and lipopolysaccharide (LPS), respectively. Intracellular UCB concentrations in HepG2 cells correlated with its levels in culture media (p < 0.001) and diminished lipid peroxidation in a dose-dependent manner (p < 0.001). Moreover, induction of HO-1 with sodium arsenite led to 2.4-fold (p = 0.01) accumulation of intracellular UCB over basal level while sodium azide-derived oxidative stress resulted in a 60% drop (p < 0.001). This decrease was ameliorated by UCB elevation in media or by simultaneous induction of HO-1. In addition, hyperbilirubinemia and liver HO-1 induction in LPS-treated rats resulted in a 2-fold accumulation of tissue UCB (p = 0.01) associated with enhanced protection against lipid peroxidation (p = 0.02). In conclusion, hyperbilirubinemia and HO-1 induction associated with inflammation and oxidative stress increase intracellular concentrations of UCB, thus enhancing the protection of cellular lipids against peroxidation. Therefore, the previously reported protective effects of hyperbilirubinemia and HO-1 induction are at least in part due to intracellular accumulation of UCB.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a antioxidancia $x metabolismus $7 D000975
- 650 _2
- $a arsenitany $x farmakologie $7 D018053
- 650 _2
- $a bilirubin $x aplikace a dávkování $x analogy a deriváty $x metabolismus $7 D001663
- 650 _2
- $a aktivace enzymů $x účinky léků $7 D004789
- 650 _2
- $a hem $x analýza $7 D006418
- 650 _2
- $a hemoxygenasa-1 $x metabolismus $7 D051547
- 650 _2
- $a buňky Hep G2 $7 D056945
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a hyperbilirubinemie $x metabolismus $7 D006932
- 650 _2
- $a peroxidace lipidů $x účinky léků $7 D015227
- 650 _2
- $a lipopolysacharidy $x aplikace a dávkování $7 D008070
- 650 _2
- $a methemalbumin $x farmakologie $7 D008705
- 650 _2
- $a oxidační stres $x účinky léků $7 D018384
- 650 _2
- $a krysa rodu Rattus $7 D051381
- 650 _2
- $a potkani Wistar $7 D017208
- 650 _2
- $a sloučeniny sodíku $x farmakologie $7 D017670
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Muchova, Lucie $u Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Zelenkova, Miroslava $u Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Vanova, Katerina $u Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Vreman, Hendrik J. $u Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
- 700 1_
- $a Wong, Ronald J. $u Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
- 700 1_
- $a Vitek, Libor $u Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 773 0_
- $w MED00009325 $t Biochimie $x 1638-6183 $g Roč. 94, č. 8 (2012), s. 1821-1827
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/22580386 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20130108 $b ABA008
- 991 __
- $a 20150107121156 $b ABA008
- 999 __
- $a ok $b bmc $g 963597 $s 798979
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2012 $b 94 $c 8 $d 1821-1827 $i 1638-6183 $m Biochimie $n Biochimie $x MED00009325
- GRA __
- $a NT11327 $p MZ0
- LZP __
- $a Pubmed-20130108
