The NF-kappaB inhibitor curcumin blocks sepsis-induced muscle proteolysis.
The NF-kappaB inhibitor curcumin blocks sepsis-induced muscle proteolysis.
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DOI：
10.1155/2008/317851
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发表时间：
2008
影响因子：
4.6
通讯作者：
Hasselgren PO
中科院分区：
文献类型：
--
作者：
Poylin V;Fareed MU;O'Neal P;Alamdari N;Reilly N;Menconi M;Hasselgren PO
我们测试了姜黄素治疗大鼠可预防脓毒症诱导的肌肉蛋白降解的假设。此外，我们确定了姜黄素对脓毒症肌肉中激活的不同蛋白水解途径的影响（即，泛素-蛋白酶体-、钙蛋白酶-和组织蛋白酶L-依赖的蛋白水解），并检测了NF-κB和p38/MAP激酶失活在姜黄素诱导的肌肉蛋白分解抑制中的作用。通过盲肠结扎和穿刺或假手术使大鼠脓毒症。用三种腹膜内剂量（600 mg/kg）的姜黄素或相应体积的溶剂处理大鼠组。蛋白质分解率测定为酪氨酸从孵育的趾长伸肌肌肉的释放。姜黄素治疗可预防脓毒症引起的肌肉蛋白质分解增加。令人惊讶的是，泛素连接酶atrogin-1和MuRF 1的上调表达不受姜黄素的影响。当脓毒症大鼠肌肉在体外用姜黄素处理时，蛋白酶体、钙蛋白酶和组织蛋白酶L依赖的蛋白质分解率降低，核NF-κB/p65表达和活性以及磷酸化（活化）p38水平降低。结果表明，脓毒症诱导的肌肉蛋白水解可以被姜黄素阻断，这种作用可能至少部分是由抑制NF-κB和p38活性引起的。结果还表明，在肌肉萎缩的治疗过程中，肌肉蛋白分解率的变化与atrogin-1和MuRF 1表达的变化之间没有绝对的相关性。
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-κB 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-κB/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-κB 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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影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
4.5
作者：
Farid M;Reid MB;Li YP;Gerken E;Durham WJ
通讯作者：
Durham WJ
影响因子：
--
作者：
Lao, Christopher D;Ruffin, Mack T 4th;Brenner, Dean E
通讯作者：
Brenner, Dean E
影响因子：
7.4
作者：
Chattopadhyay, I;Bandyopadhyay, U;Banerjee, RK
通讯作者：
Banerjee, RK
影响因子：
4.1
作者：
Deval, C;Mordier, S;Ferrara, M
通讯作者：
Ferrara, M