Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans
Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans
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DOI：
10.1093/gerona/56.7.b281
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发表时间：
2001-07-01
影响因子：
5.1
通讯作者：
Lithgow, GJ
中科院分区：
文献类型：
--
作者：
Walker, GA;White, TM;Lithgow, GJ
我们提出了热休克蛋白16 （HSP16）水平升高的证据，在本质上耐热的，长寿的秀丽隐杆线虫菌株在热应激期间和之后。编码磷脂酰肌醇3-激酶催化亚基的Age -1基因突变导致成年雌雄同体寿命延长（Age）和内在耐热性增加（Itt）。我们将年龄同步的蠕虫置于致死性和非致死性热应激下，并观察到一种针对秀丽隐杆线虫HSP16的抗体检测到的小（16-18 kd）热休克特异性多肽的积累。携带突变hx546的菌株始终比野生型菌株积累更高的HSP16水平。值得注意的是，热休克蛋白16在1岁（hx546）菌株中的过度积累在整个成年生命周期中都被观察到。将含有大肠杆菌β -半乳糖苷酶基因与秀丽隐杆线虫HSP16-41转录启动子融合的嵌合转基因引入野生型和1岁（hx546）背景。与野生型菌株相比，age-1（hx546）菌株在各种热休克和恢复条件下的热诱导表达量均有所提高。这些观察结果与年龄突变表现出耐热性和延长寿命的模型是一致的，这是由于分子伴侣水平升高的结果。
We present evidence for elevated levels of heat shock protein 16 (HSP16) in an intrinsically thermotolerant, long-lived strain of Caenorhabditis elegans during and after heat stress. Mutation of the age-1 gene, encoding a phosphatidylinositol 3-kinase catalytic subunit, results in both extended life span (Age) and increased intrinsic thermotolerance (Itt) in adult hermaphrodites. We subjected age-synchronous cohorts of worms to lethal and nonlethal thermal stress and observed the accumulation of a small (16-18 kd) heat-shock-specific polypeptide detected by an antibody raised against C. elegans HSP16. Strains carrying the mutation hx546 consistently accumulated HSP16 to higher levels than a wild-type strain. Significantly, overaccumulation of HSP16 in the age-1(hx546) strain following heat was observed throughout the adult life span. A chimeric transgene containing the Escherichia coli beta -galactosidase gene fused to a C. elegans HSP16-41 transcriptional promoter was introduced into wild-type and age-1(hx546) backgrounds. Heat-inducible expression of the transgene was elevated in the age-1(hx546) strain compared with the wild-type strain under a wide variety of heat shock and recovery conditions. These observations are consistent with a model in which Age mutations exhibit thermotolerance and extended life span as a result of elevated levels of molecular chaperones.