Fibroblasts from long-lived mutant mice exhibit increased autophagy and lower TOR activity after nutrient deprivation or oxidative stress.
Fibroblasts from long-lived mutant mice exhibit increased autophagy and lower TOR activity after nutrient deprivation or oxidative stress.
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DOI：
10.1111/j.1474-9726.2012.00833.x
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发表时间：
2012-08
期刊：
影响因子：
7.8
通讯作者：
Miller RA
中科院分区：
文献类型：
--
作者：
Wang M;Miller RA
先前的工作表明，来自长寿的垂体矮突变体的原代皮肤成纤维细胞可以抵抗多种形式的氧化和非氧化应激的致命影响。我们推测，自噬增加可能会保护Pit-1dw/dw(Snell侏儒)小鼠的成纤维细胞免受多种形式的应激。我们发现矮小来源的成纤维细胞在对氨基酸剥夺、过氧化氢和百草枯的反应中有更高水平的自噬，使用Lc3和p62作为标记。侏儒小鼠的成纤维细胞也显示出mTOR、S6K和4EBP1的磷酸化水平降低，这与这些细胞在应激后较高水平的自噬一致。在缺乏生长激素受体的突变小鼠(GHRKO小鼠)的成纤维细胞中也观察到了类似的结果，在氨基酸停用后。我们的结果表明，由TOR依赖的过程调节的自噬增加可能有助于长寿突变小鼠成纤维细胞的应激抵抗。
Previous work has shown that primary skin-derived fibroblasts from long-lived pituitary dwarf mutants resist the lethal effects of many forms of oxidative and non-oxidative stress. We hypothesized that increased autophagy may protect fibroblasts of Pit-1dw/dw (Snell dwarf) mice from multiple forms of stress. We found dwarf-derived fibroblasts had higher levels of autophagy, using LC3 and p62 as markers, in responses to amino acid deprivation, hydrogen peroxide, and paraquat. Fibroblasts from dwarf mice also showed diminished phosphorylation of mTOR, S6K and 4EBP1, consistent with the higher levels of autophagy in these cells after stress. Similar results were also observed in fibroblasts from mutant mice lacking growth hormone receptor (GHRKO mice) after amino acid withdrawal. Our results suggested that increased autophagy, regulated by TOR-dependent processes, may contribute to stress resistance in fibroblasts from long-lived mutant mice.
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