Altered accumulation of hepatic mitochondrial antioxidant proteins with age and environmental heat stress.
Altered accumulation of hepatic mitochondrial antioxidant proteins with age and environmental heat stress.
复制标题
随着年龄和环境热应激，肝线粒体抗氧化蛋白的积累发生变化。
DOI：
10.1152/japplphysiol.00610.2023
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Bloomer,StevenA
中科院分区：
文献类型：
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作者：
Haak,JodieL;Kregel,KevinC;Bloomer,StevenA
衰老会损害整体生理功能，特别是对环境压力的反应。反复的热应激会增加老年动物肝脏中的活性氧和大分子损伤，这可能是由于线粒体功能障碍。本研究的目的是通过评估关键的氧化还原敏感性和抗氧化蛋白（Sirt-3，MnSOD，Trx-2和Ref-1）来确定热应激后线粒体功能障碍的潜在机制。我们假设热应激会导致这些蛋白质在线粒体中的丰度增加，但衰老会减弱这种反应。为此，年轻（6个月）和老年（24个月）Fisher 344大鼠暴露于热应激连续两天。在每次加热试验中，在前60分钟内将结肠温度升高至41°C，然后在此温度下夹紧30分钟。未加热的动物作为对照。在第二次热应激后2和24 h，从每只动物中分离肝线粒体，然后对Sirt-3、乙酰化赖氨酸残基（Ac-K）、MnSOD、Trx-2和Ref-1进行免疫印迹。衰老增加Sirt-3，降低Ac-K。在热应激反应中，Sirt-3，Ac-K，MnSOD，和Ref-1的线粒体组分在年轻和老年动物中增加。在第二次热应激后2 h，老年动物的线粒体Trx-2下降，但在年轻的动物中没有。我们的研究结果表明，热应激反应的一些组成部分被保存与老化。然而，Trx-2的下降代表了与年龄相关的线粒体损伤和功能障碍后热stress.NEW & NOTEWORTHY我们的研究结果表明，热应激诱导的线粒体易位的Sirt-3，MnSOD，和Ref-1在年轻和老年动物。老年大鼠经历了热应激后Trx-2的下降，这表明与年龄相关的线粒体功能障碍的潜在机制。
Aging impairs overall physiological function, particularly the response to environmental stressors. Repeated heat stress elevates reactive oxygen species and macromolecular damage in the livers of aged animals, likely due to mitochondrial dysfunction. The goal of this investigation was to determine potential mechanisms for mitochondrial dysfunction after heat stress by evaluating key redox-sensitive and antioxidant proteins (Sirt-3, MnSOD, Trx-2, and Ref-1). We hypothesized that heat stress would result in greater mitochondrial abundance of these proteins, but that aging would attenuate this response. For this purpose, young (6 mo) and old (24 mo) Fisher 344 rats were exposed to heat stress on two consecutive days. During each heating trial, colonic temperature was elevated to 41°C during the first 60 min, and then clamped at this temperature for 30 min. Nonheated animals served as controls. At 2 and 24 h after the second heat stress, hepatic mitochondria were isolated from each animal, and then immunoblotted for Sirt-3, acetylated lysine residues (Ac-K), MnSOD, Trx-2, and Ref-1. Aging increased Sirt-3 and lowered Ac-K. In response to heat stress, Sirt-3, Ac-K, MnSOD, and Ref-1 increased in mitochondrial fractions in both young and old animals. At 2 h after the second heat stress, mitochondrial Trx-2 declined in old, but not in young animals. Our results suggest that some components of the response to heat stress are preserved with aging. However, the decline in Trx-2 represents a potential mechanism for age-related mitochondrial damage and dysfunction after heat stress.NEW & NOTEWORTHYOur results suggest heat stress-induced mitochondrial translocation of Sirt-3, MnSOD, and Ref-1 in young and old animals. Aged rats experienced a decline in Trx-2 after heat stress, suggesting a potential mechanism for age-related mitochondrial dysfunction.