Characterization of the proteostasis roles of glycerol accumulation, protein degradation and protein synthesis during osmotic stress in C. elegans.
Characterization of the proteostasis roles of glycerol accumulation, protein degradation and protein synthesis during osmotic stress in C. elegans.
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秀丽隐杆线虫中渗透胁迫期间甘油积累，蛋白质降解和蛋白质合成的蛋白质抑制作用的表征。
DOI：
10.1371/journal.pone.0034153
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Strange K
中科院分区：
文献类型：
--
作者：
Burkewitz K;Choe KP;Lee EC;Deonarine A;Strange K
C的暴露。线虫对高渗应激诱导的水分损失引起快速和广泛的细胞蛋白质损伤。在高渗环境中的生存关键取决于蠕虫细胞检测和降解错误折叠和聚集蛋白的能力。驯化C. elegans到轻度高渗应激抑制蛋白质损伤，并增加在更极端的高渗条件下的存活率。驯化蠕虫中蛋白质损伤的抑制可能是由于1）化学伴侣甘油的积累，2）蛋白质降解活性的上调，和/或3）细胞分子伴侣能力的增加。甘油和其他化学伴侣被广泛认为可以保护蛋白质免受高渗诱导的损伤。然而，蛋白质损伤不受抑制甘油积累或导致甘油水平急剧组成性升高的基因突变的影响。蛋白酶体和溶酶体功能的药理学或RNAi抑制以及细胞蛋白质降解活性的测量表明，蛋白质降解机制的上调在适应中不起作用。因此，分子伴侣能力的变化必须负责抑制蛋白质损伤驯化蠕虫。在C.暴露在高渗压力下的线虫然而，适应轻度高渗抑制蛋白质合成50- 70%，预计这将增加伴侣蛋白的可用性，以应对现有蛋白质的损伤。与这一想法一致，我们发现RNAi沉默基本翻译组分或急性暴露于放线菌酮导致高渗诱导的聚谷氨酰胺-YFP（Q35：：YFP）聚集的50-80%抑制。增加蛋白质产量的饮食变化也使Q35：：YFP聚集增加70- 180%。我们的研究结果直接表明，第一次抑制蛋白质翻译保护现存的蛋白质从环境压力所带来的损害，表现出重要的差异，在老化与压力诱导的蛋白质损伤，并挑战广泛持有的观点，即化学分子伴侣在高渗应激过程中积累，以保护蛋白质的结构/功能。
Exposure of C. elegans to hypertonic stress-induced water loss causes rapid and widespread cellular protein damage. Survival in hypertonic environments depends critically on the ability of worm cells to detect and degrade misfolded and aggregated proteins. Acclimation of C. elegans to mild hypertonic stress suppresses protein damage and increases survival under more extreme hypertonic conditions. Suppression of protein damage in acclimated worms could be due to 1) accumulation of the chemical chaperone glycerol, 2) upregulation of protein degradation activity, and/or 3) increases in molecular chaperoning capacity of the cell. Glycerol and other chemical chaperones are widely thought to protect proteins from hypertonicity-induced damage. However, protein damage is unaffected by gene mutations that inhibit glycerol accumulation or that cause dramatic constitutive elevation of glycerol levels. Pharmacological or RNAi inhibition of proteasome and lyosome function and measurements of cellular protein degradation activity demonstrated that upregulation of protein degradation mechanisms plays no role in acclimation. Thus, changes in molecular chaperone capacity must be responsible for suppressing protein damage in acclimated worms. Transcriptional changes in chaperone expression have not been detected in C. elegans exposed to hypertonic stress. However, acclimation to mild hypertonicity inhibits protein synthesis 50–70%, which is expected to increase chaperone availability for coping with damage to existing proteins. Consistent with this idea, we found that RNAi silencing of essential translational components or acute exposure to cycloheximide results in a 50–80% suppression of hypertonicity-induced aggregation of polyglutamine-YFP (Q35::YFP). Dietary changes that increase protein production also increase Q35::YFP aggregation 70–180%. Our results demonstrate directly for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, demonstrate important differences in aging- versus stress-induced protein damage, and challenge the widely held view that chemical chaperones are accumulated during hypertonic stress to protect protein structure/function.
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DOI：
10.1126/science.1166175
发表时间：
2009-01-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anderson LL;Mao X;Scott BA;Crowder CM
通讯作者：
Crowder CM
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
5.3
作者：
GANDHI, S;SANTELLI, J;RAOSANADI, D
通讯作者：
RAOSANADI, D
影响因子：
3.2
作者：
Chattopadhyay, MK;Kern, R;Richarme, G
通讯作者：
Richarme, G
影响因子：
7.2
作者：
Gidalevitz, Tali;Prahlad, Veena;Morimoto, Richard I.
通讯作者：
Morimoto, Richard I.