Difference between revisions of "Regueira 2009 Liver Int"
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{{Publication | {{Publication | ||
|title=Regueira T, Lepper PM, Brandt S, Ochs M, Vuda M, Takala J, Jakob SM, Djafarzadeh S (2009) Hypoxia inducible factor-1alpha induction by tumour necrosis factor-alpha, but not by toll-like receptor agonists, modulates cellular respiration in cultured human hepatocytes. Liver Int 10:1582- | |title=Regueira T, Lepper PM, Brandt S, Ochs M, Vuda M, Takala J, Jakob SM, Djafarzadeh S (2009) Hypoxia inducible factor-1alpha induction by tumour necrosis factor-alpha, but not by toll-like receptor agonists, modulates cellular respiration in cultured human hepatocytes. Liver Int 10:1582-92. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/19744167Β 19744167] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19744167Β PMID: 19744167] | ||
|authors=Regueira T, Lepper PM, Brandt S, Ochs M, Vuda M, Takala J, Jakob SM, Djafarzadeh S | |authors=Regueira T, Lepper PM, Brandt S, Ochs M, Vuda M, Takala J, Jakob SM, Djafarzadeh S | ||
|year=2009 | |year=2009 | ||
|journal=Liver Int | |journal=Liver Int | ||
|abstract=BACKGROUND/AIMS: | |abstract=BACKGROUND/AIMS: | ||
Genes encoding for some of the mitochondrial proteins are under the control of the transcriptional factor hypoxia inducible factor-1 alpha (HIF-1 alpha), which can accumulate under normoxic conditions in inflammatory states. The aim of this study was to evaluate the effects of cobalt chloride (CoCl | Genes encoding for some of the mitochondrial proteins are under the control of the transcriptional factor hypoxia inducible factor-1 alpha (HIF-1 alpha), which can accumulate under normoxic conditions in inflammatory states. The aim of this study was to evaluate the effects of cobalt chloride (CoCl<sub>2</sub>, a hypoxia mimicking agent), tumour necrosis factor-alpha (TNF-alpha) and toll-like receptor (TLR) -2, -3 and -4 agonists on HIF-1 alpha accumulation, and further on HIF-1 alpha-mediated modulation of mitochondrial respiration in cultured human hepatocytes. | ||
METHODS: | METHODS: | ||
The human hepatoma cell line HepG2 was used in this study. Cells were treated with CoCl | The human hepatoma cell line HepG2 was used in this study. Cells were treated with CoCl<sub>2</sub>, TNF-alpha and TLR-2, -3 and -4 agonists. HIF-1 alpha was determined by Western blotting and mitochondrial respiration in stimulated cells by high-resolution respirometry. | ||
RESULTS: | RESULTS: | ||
CoCl | CoCl<sub>2</sub>, TNF-alpha and TLR agonists induced the expression of HIF-1 alpha in a time-dependent fashion. TNF-alpha and CoCl<sub>2</sub>, but not TLR agonists, induced a reduction in complex I-, II- and IV-dependent mitochondrial oxygen consumption. TNF-alpha-associated reduction of cellular oxygen consumption was abolished through inhibition of HIF-1 alpha activity by chetomin (CTM). Pretreatment with cyclosporine A prevented CoCl<sub>2</sub>-induced reduction of complex I- and II-dependent mitochondrial oxygen consumption and TNF-alpha-induced reduction of complex-I-dependent respiration, implicating the involvement of the mitochondrial permeability transition pore openings. TNF-alpha and TLR-2, -3 and -4 agonists induced the expression of vascular endothelial growth factor, which was partially abolished by the blockage of HIF-1 alpha with CTM. | ||
CONCLUSIONS: | CONCLUSIONS: | ||
The data suggest that HIF-1 alpha modulates mitochondrial respiration during CoCl | The data suggest that HIF-1 alpha modulates mitochondrial respiration during CoCl<sub>2</sub> and TNF-alpha stimulation, whereas it has no effect when induced with TLR-2, -3 and -4 agonists. | ||
|mipnetlab= | |keywords=CTM; HIF-1Ξ±; High-resolution respirometry; Mitochondria; MyD88; TLRs; TNF-Ξ±; VEGF; HepG2 | ||
|mipnetlab=CH Bern Djafarzadeh S, CL Santiago Regueira T | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |||
|injuries=Ischemia-reperfusion, Hypoxia | |||
|organism=Human | |||
|tissues=Liver | |||
|preparations=Permeabilized cells | |||
|couplingstates=LEAK, OXPHOS | |||
|pathways=N, S, CIV, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 17:15, 27 March 2018
| Regueira T, Lepper PM, Brandt S, Ochs M, Vuda M, Takala J, Jakob SM, Djafarzadeh S (2009) Hypoxia inducible factor-1alpha induction by tumour necrosis factor-alpha, but not by toll-like receptor agonists, modulates cellular respiration in cultured human hepatocytes. Liver Int 10:1582-92. |
Regueira T, Lepper PM, Brandt S, Ochs M, Vuda M, Takala J, Jakob SM, Djafarzadeh S (2009) Liver Int
Abstract: BACKGROUND/AIMS: Genes encoding for some of the mitochondrial proteins are under the control of the transcriptional factor hypoxia inducible factor-1 alpha (HIF-1 alpha), which can accumulate under normoxic conditions in inflammatory states. The aim of this study was to evaluate the effects of cobalt chloride (CoCl2, a hypoxia mimicking agent), tumour necrosis factor-alpha (TNF-alpha) and toll-like receptor (TLR) -2, -3 and -4 agonists on HIF-1 alpha accumulation, and further on HIF-1 alpha-mediated modulation of mitochondrial respiration in cultured human hepatocytes.
METHODS: The human hepatoma cell line HepG2 was used in this study. Cells were treated with CoCl2, TNF-alpha and TLR-2, -3 and -4 agonists. HIF-1 alpha was determined by Western blotting and mitochondrial respiration in stimulated cells by high-resolution respirometry.
RESULTS: CoCl2, TNF-alpha and TLR agonists induced the expression of HIF-1 alpha in a time-dependent fashion. TNF-alpha and CoCl2, but not TLR agonists, induced a reduction in complex I-, II- and IV-dependent mitochondrial oxygen consumption. TNF-alpha-associated reduction of cellular oxygen consumption was abolished through inhibition of HIF-1 alpha activity by chetomin (CTM). Pretreatment with cyclosporine A prevented CoCl2-induced reduction of complex I- and II-dependent mitochondrial oxygen consumption and TNF-alpha-induced reduction of complex-I-dependent respiration, implicating the involvement of the mitochondrial permeability transition pore openings. TNF-alpha and TLR-2, -3 and -4 agonists induced the expression of vascular endothelial growth factor, which was partially abolished by the blockage of HIF-1 alpha with CTM.
CONCLUSIONS: The data suggest that HIF-1 alpha modulates mitochondrial respiration during CoCl2 and TNF-alpha stimulation, whereas it has no effect when induced with TLR-2, -3 and -4 agonists. β’ Keywords: CTM; HIF-1Ξ±; High-resolution respirometry; Mitochondria; MyD88; TLRs; TNF-Ξ±; VEGF; HepG2
β’ O2k-Network Lab: CH Bern Djafarzadeh S, CL Santiago Regueira T
Labels: MiParea: Respiration
Stress:Ischemia-reperfusion, Hypoxia Organism: Human Tissue;cell: Liver Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
