运动诱导的去卵巢小鼠骨骼肌线粒体保护：肌源性E2合成独立机制

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology Pub Date : 2025-06-21 DOI:10.1016/j.redox.2025.103735

Xu Tian, Yi Hu, Tao Li, Fangfang Yu, Tingting Li, Xiangyang Tian, Yiwei Feng, Qiuling Zhong, Yifan Meng, Wei Chen, Rengfei Shi

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引用次数: 0

摘要

骨骼肌是一种对17β-雌二醇（E2）敏感的组织，由于绝经后E2缺乏和随后的线粒体功能障碍，骨骼肌容易加速衰老。虽然外源性E2治疗已被证明可以保护去卵巢啮齿类动物免受线粒体损伤，但运动诱导的骨骼肌局部E2产生对线粒体功能的影响仍有待确定。本研究探讨了运动介导的去卵巢小鼠线粒体保护和肌源性E2的作用。

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Exercise-induced mitochondrial protection in skeletal muscle of ovariectomized mice: A myogenic E2 synthesis-independent mechanism

Background

Skeletal muscle, a 17β-estradiol (E₂)-sensitive tissue, is prone to accelerated aging due to postmenopausal E₂ deficiency and subsequent mitochondrial dysfunction. While exogenous E₂ treatment has been shown to protect against mitochondrial damage in ovariectomized rodents, the impact of exercise-induced local E₂ production in skeletal muscle on mitochondrial function remains to be determined. This study investigated exercise-mediated mitochondrial protection in ovariectomized mice and the contribution of myogenic E₂.

Methods

Female C57BL/6J mice (8-week-old) were divided into Sham, OVX, and OVX + ET groups (N = 12). OVX mice underwent bilateral ovariectomy, with the OVX + ET group performing 8 weeks of treadmill exercise starting 10 weeks post-surgery. Functional tests (grip strength, fatigue resistance) and gastrocnemius analyses (morphology, mitochondrial function, E2/antioxidant levels, and protein expression) were conducted. Parallel experiments in muscle-specific aromatase knockout (MS-ARO-CKO) mice included E2 supplementation via subdermal pellets.

Results

18 weeks after ovariectomy (OVX), C57BL/6J mice exhibited significant reductions in grip strength (∼30 %), rotarod performance (∼57 %), and grid hanging performance (∼92 %). Concomitantly, OVX led to marked decreases in mitochondrial respiration (p < 0.05) and antioxidant capacity (p < 0.05) in the gastrocnemius muscle, accompanied by alterations in mitochondrial quality control and antioxidant signaling proteins (p < 0.05). Exercise intervention effectively attenuated these OVX-induced deficits, accompanied by a 66 % increase in E₂ levels and upregulation of aromatase (ARO) activity and expression (p < 0.05). In MS-ARO-CKO mice model, exercise failed to improve the impaired antioxidant capacity induced by OVX. However, exercise, similar to estrogen supplementation, restored mitochondrial function and related protein expression abnormalities induced by OVX (p < 0.05).

Conclusions

Our findings demonstrate that the protective effects of exercise on skeletal muscle mitochondria involve multiple mechanisms, independent myogenic E₂ Synthesis, providing novel insights for improving skeletal muscle health in postmenopausal women.

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来源期刊

Redox Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

19.90

自引率

3.50%

发文量

318

审稿时长

25 days

期刊介绍： Redox Biology is the official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe. It is also affiliated with the International Society for Free Radical Research (SFRRI). This journal serves as a platform for publishing pioneering research, innovative methods, and comprehensive review articles in the field of redox biology, encompassing both health and disease. Redox Biology welcomes various forms of contributions, including research articles (short or full communications), methods, mini-reviews, and commentaries. Through its diverse range of published content, Redox Biology aims to foster advancements and insights in the understanding of redox biology and its implications.