Tumor necrosis factor increases mitochondrial oxidant production and induces expression of uncoupling protein-2 in the regenerating rat liver

Lee, F. Y. Janet; Li, Yunbo; Zhu, Hong; Yang, Shiqi; Lin, Hui-Kuan; Trush, Michael A.; Diehl, Anna Mae

doi:10.1002/hep.510290320

Cited by 153 publications

(142 citation statements)

References 73 publications

(113 reference statements)

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…These authors tested the hypothesis that tumour necrosis factor-α increases mitochondrial oxidant production after partial hepatectomy. They observed that the tumour necrosis factor-α-dependent increase in oxidant production by liver mitochondria promoted UCP2 induction, which may represent an antioxidant defence mechanism [122]. The same authors observed an increased level of UCP2 in hepatocytes cultured in the presence of lipid emulsion [126].…”

Section: Regulation Of Reactive Oxygen Species (Ros)mentioning

confidence: 93%

“…ROS are also produced in the destruction of cells during infection, in the degradation of fatty acids and other molecules by peroxisomes, and as byproducts of processes that defend against toxic chemicals [121]. Excess superoxide ions may cause peroxidation of phospholipids, damage mitochondrial DNA, alter proteins or induce transcriptional factors [122]. Oxygen radicals can damage DNA, phospholipids and proteins, and also affect the transcription of genes.…”

Section: Regulation Of Reactive Oxygen Species (Ros)mentioning

confidence: 99%

“…Sequencing of DNA upstream of the transcriptional start site of the mouse and human UCP2 genes also revealed the presence of a consensus site for nuclear factor κB (C. Pecqueur, S. Raimbault and D. Ricquier, unpublished work). Although the functional activity of these binding sites for various factors has not yet been demonstrated, a possible role for these sites was suggested by the observed effects of thiazolidinediones, phorbol esters and endotoxin on UCP2 mRNA levels in animals or in cultures [122,[171][172][173][174][175]. Yamada et al [148] reported that 1250 bp of the promoter region of the mouse UCP2 gene showed significant promoter activity in L6, 3T3-L1, HeLa, NIH 3T3 and CV-1 cells, in agreement with the ubiquitous expression of the gene.…”

Section: Functional Organization Of the Ucp2 And Ucp3 Genesmentioning

confidence: 99%

See 2 more Smart Citations

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

610

115

View full text Add to dashboard Cite

Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton\anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest that UCP2 and UCP3 play a part in

show abstract

Section: Regulation Of Reactive Oxygen Species (Ros)mentioning

confidence: 93%

Section: Regulation Of Reactive Oxygen Species (Ros)mentioning

confidence: 99%

Section: Functional Organization Of the Ucp2 And Ucp3 Genesmentioning

confidence: 99%

See 1 more Smart Citation

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

610

115

View full text Add to dashboard Cite

show abstract

“…Inhibiting BAT UCP-1 or disruption of UCP-2 gene in mice stimulates ROS production, while both the ROS-inducing agent tertbutyl hydroperoxide (TBHP) and tumour necrosis factor-a (TNFa) can induce hepatocyte UCP-2 mRNA; this suggests that UCPs may also serve as an antioxidant defence mechanism (Negre-Salvayre et al, 1997;Cortez-Pinto et al, 1999;Lee et al, 1999;Arsenijevic et al, 2000). Perhaps consistent with this is the observation that fatty livers from ob/ob mice or ethanol-fed lean mice show up-regulation of hepatic transcripts for UCP-2, while hepatocyte death is not increased (Rashid et al, 1999).…”

Section: Experimental Therapeuticsmentioning

confidence: 99%

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

et al. 2002

View full text Add to dashboard Cite

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (710%, P=0.03) and fat mass (720%, P50.01) accompanied by a marked decrease in plasma leptin (759%, P50.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P50.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P50.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P50.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.

show abstract

“…24,25 UCP2 has wide tissue distribution, but in normal liver it has been localized mainly to Kupffer cells. 26 Increased hepatic UCP2 mRNA levels were found after partial hepatectomy, 27 although the cell-specific localization and functional significance of this phenomenon is unclear. It has been suggested that UCP2 may be protective by limiting ROS production in livers exposed to excess fuel supply (e.g., in fatty liver), although the increased presence of UCP2 in these conditions is believed to compromise ATP synthesis at the same time, and genetic ablation of the UCP2 gene in ob/ob mice actually results in no obvious long-term effects on liver steatosis.…”

mentioning

confidence: 99%

Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice

et al. 2004

View full text Add to dashboard Cite

The control of liver regeneration remains elusive. Because reactive oxygen species (ROS) are able to mediate cell growth arrest and activate proteins that inhibit the cell cycle, ROS production may have a negative impact on liver regeneration. We examined how liver regeneration is affected by uncoupling protein-2 (UCP2), an inner mitochondrial membrane carrier that senses and negatively regulates superoxide production. Liver regeneration was monitored up to 5 days and was found to be significantly delayed in UCP2 ؊/؊ mice after partial hepatectomy. Apoptosis rates in UCP2 ؉/؉ and UCP2 ؊ /؊ liver remnants were similar, while parameters of cell proliferation indicated a diminished response in UCP2 ؊ /؊ mice with corresponding changes in the expression of key cell cycle regulatory proteins and prolonged activation of stress-responsive protein kinase p38. Levels of malondialdehyde, a marker of ROS generation and oxidant stress, were elevated in UCP2 ؊ /؊ livers at every examined time point. Liver remnants of UCP2 ؉ /؉ mice 48 hours post-hepatectomy showed a fourfold increase in the expression of UCP2 protein primarily detected in hepatocytes. In conclusion, our results suggest that absent or insufficient UCP2 function in the regenerating liver results in increased ROS production and negatively modulates the control of cell cycle.

show abstract

Tumor necrosis factor increases mitochondrial oxidant production and induces expression of uncoupling protein-2 in the regenerating rat liver

Cited by 153 publications

References 73 publications

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice

Contact Info

Product

Resources

About