The NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="E1"><mml:mi>κ</mml:mi></mml:math>B Inhibitor Curcumin Blocks Sepsis-Induced Muscle Proteolysis

Poylin, Vitaliy; Fareed, Moin U.; O’Neal, Patrick; Alamdari, Nima; Reilly, Natasha; Menconi, Michael J.; Hasselgren, Per Olof

doi:10.1155/2008/317851

Cited by 56 publications

(39 citation statements)

References 53 publications

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“…The reason for this discrepancy is likely related to the longer time points investigated in the study reported herein. It should also be mentioned that we decided to administer curcumin through the intraperitoneal route, as in previously reported studies, [29][30][31] to minimize possible differences in curcumin administration linked to the fact that the sickest animals on the MCD diet would have been likely to limit food intake.…”

Section: Discussionmentioning

confidence: 99%

Curcumin limits the fibrogenic evolution of experimental steatohepatitis

Vizzutti

Provenzano

Galastri

et al. 2010

Laboratory Investigation

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Nonalcoholic steatohepatitis is characterized by the association of steatosis with hepatic cell injury, lobular inflammation and fibrosis. Curcumin is known for its antioxidant, anti-inflammatory and antifibrotic properties. The aim of this study was to test whether the administration of curcumin limits fibrogenic evolution in a murine model of nonalcoholic steatohepatitis. Male C57BL/6 mice were divided into four groups and fed a diet deficient in methionine and choline (MCD) or the same diet supplemented with methionine and choline for as long as 10 weeks. Curcumin (25 mg per mouse) or its vehicle (DMSO) was administered intraperitoneally every other day. Fibrosis was assessed by Sirius red staining and histomorphometry. Intrahepatic gene expression was measured by quantitative PCR. Hepatic oxidative stress was evaluated by staining for 8-OH deoxyguanosine. Myofibroblastic hepatic stellate cells (HSCs) were isolated from normal human liver tissue. The increase in serum ALT caused by the MCD diet was significantly reduced by curcumin after 4 weeks. Administration of the MCD diet was associated with histological steatosis and necro-inflammation, and this latter was significantly reduced in mice receiving curcumin. Curcumin also inhibited the generation of hepatic oxidative stress. Fibrosis was evident after 8 or 10 weeks of MCD diet and was also significantly reduced by curcumin. Curcumin decreased the intrahepatic gene expression of monocyte chemoattractant protein-1, CD11b, procollagen type I and tissue inhibitor of metalloprotease (TIMP)-1, together with protein levels of a-smooth muscle-actin, a marker of fibrogenic cells. In addition, curcumin reduced the generation of reactive oxygen species in cultured HSCs and inhibited the secretion of TIMP-1 both in basal conditions and after the induction of oxidative stress. In conclusion, curcumin administration effectively limits the development and progression of fibrosis in mice with experimental steatohepatitis, and reduces TIMP-1 secretion and oxidative stress in cultured stellate cells.

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Section: Discussionmentioning

confidence: 99%

Curcumin limits the fibrogenic evolution of experimental steatohepatitis

Vizzutti

Provenzano

Galastri

et al. 2010

Laboratory Investigation

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“…NF-B activation upregulates muscle RING finger protein 1 (MuRF1), a mediator of muscle atrophy, and inhibits the protein gain [Cai et al, 2004]. On the other hand, inhibition of NF-B blocks sepsis-induced muscle proteolysis without changes in MuRF1 and atrogin-1 expressions [Poylin et al, 2008]. It has also been reported that the inhibition of NF-B by HSP70 prevents the skeletal muscle atrophy [Senf et al, 2008;Dodd et al, 2009].…”

Section: Protein Content In C2c12 Myotubesmentioning

confidence: 99%

Possible Role of NF-ĸB Signals in Heat Stress-Associated Increase in Protein Content of Cultured C2C12 Cells

Ohno

Yamada

Sugiura

et al. 2011

Cells Tissues Organs

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Heat stress is one of the hypertrophic stimuli on mammalian skeletal muscle. Nuclear factor-ĸB (NF-ĸB) signaling plays an important role in the regulation of skeletal muscle mass. However, the effects of heat stress on NF-ĸB signaling in skeletal muscle cells remain unclear. Effects of heat stress and/or administration of BAY11-7082, an inhibitor of NF-ĸB, on NF-ĸB signals and protein content of skeletal muscle were studied by using cell culture system. Differentiated mouse myoblasts (C2C12) were subjected to either (1) control (cultured at 37°C without BAY11-7082), (2) heat stress at 41°C for 60 min, (3) BAY11-7082 administration (1.25 µM) or (4) heat stress combined with BAY11-7082 administration. Heat shock protein 72 (HSP72) was upregulated by heat stress with or without administration of BAY11-7082. The increase in inhibitor of ĸBα (IĸBα), which regulates the phosphorylation of NF-ĸB, and the decrease in phosphorylated NF-ĸB were also induced by administration of BAY11-7082 and/or heat stress. Protein content in C2C12 cells was increased by the administration of BAY11-7082 with a semi-logarithm fashion. Significant increases in the protein content of C2C12 cells were observed 48 h following heating with or without administration of BAY11-7082. These observations suggest that heat stress might increase muscle protein through the downregulation of NF-ĸB signaling. Inhibition of NF-ĸB induced by application of heat stress might be one of the hypertrophic stimuli on skeletal muscle cells.

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“…Because stimulated gene transcription is involved in muscle wasting, it is not surprising that increased expression and activity of certain transcription factors, including NF-B (4,28,29,40), CCAAT-enhancer-binding protein (C/EBP)-␤ and C/EBP␦ (27,46), and FOXO1 and FOXO3a (32,35,49), play a role in muscle wasting.…”

mentioning

confidence: 99%

Sepsis and glucocorticoids downregulate the expression of the nuclear cofactor PGC-1β in skeletal muscle

Menconi¹,

Arany

Alamdari³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Smith IJ, Tizio S, Hasselgren P. Sepsis and glucocorticoids downregulate the expression of the nuclear cofactor PGC-1␤ in skeletal muscle. Am J Physiol Endocrinol Metab 299: E533-E543, 2010. First published July 20, 2010; doi:10.1152/ajpendo.00596.2009.-Muscle wasting during sepsis is at least in part regulated by glucocorticoids and is associated with increased transcription of genes encoding the ubiquitin ligases atrogin-1 and muscle-specific RING-finger protein-1 (MuRF1). Recent studies suggest that muscle atrophy caused by denervation is associated with reduced expression of the nuclear cofactor peroxisome proliferator-activated receptor-␥ coactivator (PGC)-1␤ and that PGC-1␤ may be a repressor of the atrogin-1 and MuRF1 genes. The influence of other muscle-wasting conditions on the expression of PGC-1␤ is not known. We tested the influence of sepsis and glucocorticoids on PGC-1␤ and examined the potential link between downregulated PGC-1␤ expression and upregulated atrogin-1 and MuRF1 expression in skeletal muscle. Sepsis in rats and mice and treatment with dexamethasone resulted in downregulated expression of PGC-1␤ and increased expression of atrogin-1 and MuRF1 in the fast-twitch extensor digitorum longus muscle, with less pronounced changes in the slow-twitch soleus muscle. In additional experiments, adenoviral gene transfer of PGC-1␤ into cultured C 2C12 myotubes resulted in a dose-dependent decrease in atrogin-1 and MuRF1 mRNA levels. Treatment of cultured C 2C12 myotubes with dexamethasone or PGC-1␤ small interfering RNA (siRNA) resulted in downregulated PGC-1␤ expression and increased protein degradation. Taken together, our results suggest that sepsis-and glucocorticoid-induced muscle wasting may, at least in part, be regulated by decreased expression of the nuclear cofactor PGC-1␤.peroxisome proliferator-activated receptor-␥ coactivator-1␤; muscle wasting; transcription factors; muscle mass SEPSIS-INDUCED MUSCLE WASTING is associated with increased transcription of genes in the ubiquitin-proteasome proteolytic pathway, in particular the genes encoding the ubiquitin ligases atrogin-1 and muscle-specific RING-finger protein-1 (MuRF1) (7,10,44). Because stimulated gene transcription is involved in muscle wasting, it is not surprising that increased expression and activity of certain transcription factors, including NF-B (4, 28, 29, 40), CCAAT-enhancer-binding protein (C/EBP)-␤ and C/EBP␦ (27,46), and FOXO1 and FOXO3a (32,35,49), play a role in muscle wasting.In addition to being regulated by transcription factors, gene transcription is also influenced by nuclear cofactors acting as activators or repressors (14). The potential role of nuclear cofactors in muscle wasting was illustrated in recent studies in our laboratory, in which we found evidence that glucocorticoid-induced muscle atrophy may, at least in part, be regulated by the nuclear cofactor p300 (47, 48).An important group of nuclear cofactors that may also participate in the regulation of muscle mass are members of the peroxisome proliferato...

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The NF-κB Inhibitor Curcumin Blocks Sepsis-Induced Muscle Proteolysis

Cited by 56 publications

References 53 publications

Curcumin limits the fibrogenic evolution of experimental steatohepatitis

Curcumin limits the fibrogenic evolution of experimental steatohepatitis

Possible Role of NF-ĸB Signals in Heat Stress-Associated Increase in Protein Content of Cultured C2C12 Cells

Sepsis and glucocorticoids downregulate the expression of the nuclear cofactor PGC-1β in skeletal muscle

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