Cytoskeletal regulation dominates temperature-sensitive proteomic changes of hibernation in forebrain of 13-lined ground squirrels.

Cytoskeletal regulation dominates temperature-sensitive proteomic changes of hibernation in forebrain of 13-lined ground squirrels.
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DOI:
10.1371/journal.pone.0071627
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Martin SL
Martin SL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hindle AG;Martin SL

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13-衬地松鼠(Ictidomys tridecemlineatus)是专性冬眠动物,每年在夏季恒温和冬季异温之间过渡-其中它们利用间歇性的麻痹发作。尽管冬眠时大脑缺血,觉醒时大脑迅速再灌注,冬眠动物的大脑仍然能抵抗损伤,每年春天,动物的神经系统都完好无损。我们假设大脑中的蛋白质变化是冬季神经保护的基础。为了确定候选蛋白质,我们采用了一种敏感的二维凝胶电泳方法,以量化从地松鼠在两个夏季,四个冬季和秋季过渡状态制备的前脑提取物之间的蛋白质差异。使用LC-MS/MS确定各组之间的蛋白质不同。只有84个蛋白质点之间的定义的冬眠状态变化显着。前脑蛋白质组中的蛋白质变化主要分为两种相互模式,具有很强的体温依赖性。在秋季的动物中测试了体温的重要性;这些秋季动物在夏季恒温和冬季异温之间的过渡中偶尔使用麻痹,体温反映了4至21°C的环境温度。不像冷-迟钝的秋地松鼠,暖-迟钝的个体与恒温动物非常相似,这表明在迟钝的冬眠动物中观察到的变化是由体温定义的,而不是迟钝本身。代谢酶在很大程度上保持不变,尽管在年度和torpor-arousal周期变化的代谢活动。相反,大多数观察到的变化是细胞骨架蛋白及其调节剂。而细胞骨架结构蛋白往往有季节性差异,即,在夏季恒温和冬季异温之间,它们的调节蛋白受体温的影响更大。微管组装和拆卸调节蛋白二氢嘧啶酶相关蛋白和stathmin的各种异构体的丰度的变化表明,在休眠-觉醒周期中,细胞骨架快速重组的机制。
13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy – wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase-related protein and stathmin suggested mechanisms for rapid cytoskeletal reorganization on return to euthermy during torpor-arousal cycles.
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