Expression of NF-?B and downstream antioxidant genes in skeletal muscle of hibernating ground squirrels, Spermophilus tridecemlineatus
Expression of NF-?B and downstream antioxidant genes in skeletal muscle of hibernating ground squirrels, Spermophilus tridecemlineatus
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DOI：
10.1002/cbf.1832
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发表时间：
2012-03-01
影响因子：
3.6
通讯作者：
Storey, Kenneth B.
中科院分区：
文献类型：
--
作者：
Allan, Marcus E.;Storey, Kenneth B.
许多小型哺乳动物通过冬眠来度过冬天，进入长时间的寒冷麻痹，其间穿插着短暂的唤醒期，恢复到体温正常。这种循环伴随着氧消耗、组织灌注和ATP周转的广泛变化，特别是唤醒期是具有挑战性的，因为氧化应激与支持棕色脂肪组织和骨骼肌产热所需的氧消耗的巨大增加有关。需要良好的抗氧化防御。本研究分析了氧化还原敏感的转录因子，NF-？B，在骨骼肌上的六个点上的torporarousal周期，以了解其在冬眠期间的调节和作用。免疫印迹法分析NF-？B p50和p65亚基水平，核与细胞质定位和DNA结合活性以及I？Ba抑制剂和磷酸化I的激酶IKK？引发其与NF-的解离？B。这些数据通常与NF-？B在进入麻痹的反应，包括自动上调p50亚基在早期麻痹和升高I？兴奋时的蛋白质。蛋白质水平的两个下游抗氧化剂的目标表现出差异调节，锰超氧化物歧化酶（MnSOD）上升，在早期麻木与血红素加氧酶1（HO-1）增加在早期觉醒。p50、p65、HO-1和MnSOD的mRNA转录水平在不同的觉醒周期也有不同的表达。结果表明，抗氧化防御上调在特定阶段的torporarousal周期和NF-？B介导这种保护性反应。版权所有（c）2011约翰威利父子有限公司
Many small mammals survive the winter by hibernating, entering long periods of cold torpor that are interspersed with brief periods of arousal back to euthermia. This cycling is accompanied by wide changes in oxygen consumption, perfusion of tissues and ATP turnover, and the arousal period in particular is challenging because of oxidative stress associated with the huge increase in oxygen consumption needed to support thermogenesis by brown adipose tissue and skeletal muscle. Well-developed antioxidant defences are needed. The present study analyses responses of the redox-sensitive transcription factor, NF-?B, in skeletal muscle over six points on the torporarousal cycle to gain insight into its regulation and role during hibernation. Immunoblotting was used to analyse NF-?B p50 and p65 subunit levels, nuclear versus cytoplasmic localization and DNA-binding activity as well as levels and phosphorylation state of the I?Ba inhibitor and the kinase IKK that phosphorylates I?Ba to trigger its dissociation from NF-?B. The data were generally consistent with an activation of NF-?B during the entrance into torpor with responses including an auto-up-regulation of p50 subunits seen during early torpor and elevated I?Ba protein during arousal. Protein levels of two downstream antioxidant targets showed differential regulation, Mn-superoxide dismutase (MnSOD) rising during early torpor versus heme oxygenase 1 (HO-1) increasing during early arousal. The mRNA transcript levels of p50, p65, HO-1 and MnSOD also showed differential expression over the torporarousal cycle. The results suggest that antioxidant defences are up-regulated at specific phases of the torporarousal cycle and that NF-?B mediates such protective responses. Copyright (c) 2011 John Wiley & Sons, Ltd.