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The NF-kappaB inhibitor curcumin blocks sepsis-induced muscle proteolysis.

Poylin V, Fareed MU, O'Neal P, Alamdari N, Reilly N, Menconi M, Hasselgren PO - Mediators Inflamm. (2008)

Bottom Line: Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles.Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin.When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-kappaB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

ABSTRACT
We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-kappaB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-kappaB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-kappaB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting.

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Related in: MedlinePlus

The heat shock response is not involvedin the effects of curcumin on protein breakdown in incubated muscles fromseptic rats. (a) Muscles from septic rats (16 hours after CLP) were incubated for 2 hours in the absence (control) or presence of 100 μM curcumin followed by determination of hsp-70 levels by Western blotting. Similar results were observed in three repeated experiments. (b) Protein breakdown rates in muscles from septic rats incubated for 2 hours in the absence or presence of 100 μM curcumin or 100 μM curcumin + 100 mM quercetin. Results are means ± SEM with n = 12 in each group. *P < .05 versus control by ANOVA.
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fig9: The heat shock response is not involvedin the effects of curcumin on protein breakdown in incubated muscles fromseptic rats. (a) Muscles from septic rats (16 hours after CLP) were incubated for 2 hours in the absence (control) or presence of 100 μM curcumin followed by determination of hsp-70 levels by Western blotting. Similar results were observed in three repeated experiments. (b) Protein breakdown rates in muscles from septic rats incubated for 2 hours in the absence or presence of 100 μM curcumin or 100 μM curcumin + 100 mM quercetin. Results are means ± SEM with n = 12 in each group. *P < .05 versus control by ANOVA.

Mentions: In previous studies, curcumin induced the heat shock response as determined by the induction of hsp70 expression [47]. We next tested whether a similar mechanism may be involved in the effects of curcumin observed in the present experiments. When muscles from septic rats were incubated in the presence of 100 μM curcumin, no changes in hsp70 levels were noticed (Figure 9(a)). In addition, the heat shock inhibitor quercetin [48] did not influence the effect of curcumin on protein degradation in muscles from septic rats (Figure 9(b)). Thus, induction of the heat shock response is probably not a major mechanism by which curcumin inhibits sepsis-induced muscle proteolysis.


The NF-kappaB inhibitor curcumin blocks sepsis-induced muscle proteolysis.

Poylin V, Fareed MU, O'Neal P, Alamdari N, Reilly N, Menconi M, Hasselgren PO - Mediators Inflamm. (2008)

The heat shock response is not involvedin the effects of curcumin on protein breakdown in incubated muscles fromseptic rats. (a) Muscles from septic rats (16 hours after CLP) were incubated for 2 hours in the absence (control) or presence of 100 μM curcumin followed by determination of hsp-70 levels by Western blotting. Similar results were observed in three repeated experiments. (b) Protein breakdown rates in muscles from septic rats incubated for 2 hours in the absence or presence of 100 μM curcumin or 100 μM curcumin + 100 mM quercetin. Results are means ± SEM with n = 12 in each group. *P < .05 versus control by ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279164&req=5

fig9: The heat shock response is not involvedin the effects of curcumin on protein breakdown in incubated muscles fromseptic rats. (a) Muscles from septic rats (16 hours after CLP) were incubated for 2 hours in the absence (control) or presence of 100 μM curcumin followed by determination of hsp-70 levels by Western blotting. Similar results were observed in three repeated experiments. (b) Protein breakdown rates in muscles from septic rats incubated for 2 hours in the absence or presence of 100 μM curcumin or 100 μM curcumin + 100 mM quercetin. Results are means ± SEM with n = 12 in each group. *P < .05 versus control by ANOVA.
Mentions: In previous studies, curcumin induced the heat shock response as determined by the induction of hsp70 expression [47]. We next tested whether a similar mechanism may be involved in the effects of curcumin observed in the present experiments. When muscles from septic rats were incubated in the presence of 100 μM curcumin, no changes in hsp70 levels were noticed (Figure 9(a)). In addition, the heat shock inhibitor quercetin [48] did not influence the effect of curcumin on protein degradation in muscles from septic rats (Figure 9(b)). Thus, induction of the heat shock response is probably not a major mechanism by which curcumin inhibits sepsis-induced muscle proteolysis.

Bottom Line: Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles.Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin.When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-kappaB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

ABSTRACT
We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-kappaB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-kappaB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-kappaB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting.

Show MeSH
Related in: MedlinePlus