PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.
PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.
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DOI：
10.1371/journal.pone.0059726
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hasselgren PO
中科院分区：
文献类型：
--
作者：
Castillero E;Alamdari N;Aversa Z;Gurav A;Hasselgren PO
fox01参与糖皮质激素和败血症诱导的肌肉萎缩，部分反映了atroggin -1和MuRF1的调节。在肌肉萎缩中影响FOXO1表达的机制尚不清楚。我们假设转录因子过氧化物酶体增殖物激活受体β/δ (PPARβ/δ)在脓毒症和糖皮质激素治疗期间上调肌肉FOXO1的表达和活性，下游上调atroggin -1和MuRF1的表达，抑制PPARβ/δ活性可以防止肌肉萎缩。我们发现在培养的肌管中激活PPARβ/δ增加FOXO1活性，atroggin -1和MuRF1表达，蛋白质降解和肌管萎缩。地塞米松治疗肌管可增加PPARβ/δ的表达和活性。PPARβ/δ阻滞剂或siRNA可抑制地塞米松诱导的FOXO1激活、atroggin -1和MuRF1表达、蛋白降解和肌管萎缩。重要的是，用PPARβ/δ抑制剂治疗可以预防地塞米松或败血症引起的大鼠肌肉萎缩。目前的研究结果表明，在糖皮质激素和败血症诱导的肌肉萎缩中，PPARβ/δ调节FOXO1的激活，用PPARβ/δ抑制剂治疗可以改善这些情况下的肌肉质量损失。
FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions.
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影响因子：
38.9
作者：
De Jonghe, B;Bastuji-Garin, S;Brochard, L
通讯作者：
Brochard, L
影响因子：
4.8
作者：
Coll, Teresa;Alvarez-Guardia, David;Vazquez-Carrera, Manuel
通讯作者：
Vazquez-Carrera, Manuel
DOI：
10.1152/ajpregu.00858.2009
发表时间：
2010-08-01
影响因子：
2.8
作者：
Alamdari, Nima;Smith, Ira J.;Hasselgren, Per-Olof
通讯作者：
Hasselgren, Per-Olof
影响因子：
56.9
作者：
Brunet, A;Sweeney, LB;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1139/o11-082
发表时间：
2012-04-01
期刊：
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
影响因子：
--
作者：
Chamberlain, Wei;Gonnella, Patricia;Hasselgren, Per-Olof
通讯作者：
Hasselgren, Per-Olof