{"title":"下坡跑步通过AMPK通路诱导大鼠比目鱼肌线粒体自噬。","authors":"Huayu Shang, Ranggui Ma, Shengju Chen, Hao Deng, Mengyu Li, Shiqiao Zheng, He Zhang, Duo Zhang, Tianai Yang, Ying Yang, Zhi Xia","doi":"10.1007/s13105-025-01093-8","DOIUrl":null,"url":null,"abstract":"<p><p>Eccentric exercise is known to induce more pronounced muscle damage associated with delayed-onset muscle soreness than concentric exercise. This study aimed to investigate whether AMP-activated protein kinase (AMPK) pathway participates in control of mitophagy in rat skeletal muscle in response to downhill running. Eighty-eight male Sprague-Dawley rats were exercised on a treadmill tilted at 16° decline at 16 m·min<sup>- 1</sup> for 90 min, with the soleus muscle sampled at 0 h, 12 h, 24 h, 48 h and 72 h after exercise. The AMPK inhibitor compound C or AMPK activator AICAR or saline was injected intraperitoneally 20 min before exercise. After downhill treadmill running, the skeletal muscle mitochondrial structure appeared to be abnormal and contained mitophagosomes; the expression levels of AMPK phosphorylation, cyclophilin D (CypD), cytochrome C (CytC), mitochondrial FK506-binding protein 8 (FKBP8), microtubule-associated protein 1 light chain 3 (LC3), and the co-localization of FKBP8 with LC3 and mitochondria with dynamin-related protein 1 (Drp1), lysosomal-associated membrane protein 2 (LAMP2) were significantly higher; the expression levels of mechanistic target of rapamycin (mTOR Ser2448) phosphorylation and heat shock protein 60 (HSP60), mitochondrial respiratory complex I (NDUFB8) and complex III (UQCRC2), and adenosine triphosphate (ATP) content were significantly lower than those in the C group. Further study showed that the effect of downhill treadmill running was partly blocked by compound C and strengthened by AICAR. A session of downhill treadmill running activated the AMPK pathway and promoted LC3 co-localizations with mitochondria and FKBP8, and induced mitophagy and mitochondrial damage within rat skeletal muscle.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Downhill running induced mitophagy in rat soleus muscle via the AMPK pathway.\",\"authors\":\"Huayu Shang, Ranggui Ma, Shengju Chen, Hao Deng, Mengyu Li, Shiqiao Zheng, He Zhang, Duo Zhang, Tianai Yang, Ying Yang, Zhi Xia\",\"doi\":\"10.1007/s13105-025-01093-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Eccentric exercise is known to induce more pronounced muscle damage associated with delayed-onset muscle soreness than concentric exercise. This study aimed to investigate whether AMP-activated protein kinase (AMPK) pathway participates in control of mitophagy in rat skeletal muscle in response to downhill running. Eighty-eight male Sprague-Dawley rats were exercised on a treadmill tilted at 16° decline at 16 m·min<sup>- 1</sup> for 90 min, with the soleus muscle sampled at 0 h, 12 h, 24 h, 48 h and 72 h after exercise. The AMPK inhibitor compound C or AMPK activator AICAR or saline was injected intraperitoneally 20 min before exercise. After downhill treadmill running, the skeletal muscle mitochondrial structure appeared to be abnormal and contained mitophagosomes; the expression levels of AMPK phosphorylation, cyclophilin D (CypD), cytochrome C (CytC), mitochondrial FK506-binding protein 8 (FKBP8), microtubule-associated protein 1 light chain 3 (LC3), and the co-localization of FKBP8 with LC3 and mitochondria with dynamin-related protein 1 (Drp1), lysosomal-associated membrane protein 2 (LAMP2) were significantly higher; the expression levels of mechanistic target of rapamycin (mTOR Ser2448) phosphorylation and heat shock protein 60 (HSP60), mitochondrial respiratory complex I (NDUFB8) and complex III (UQCRC2), and adenosine triphosphate (ATP) content were significantly lower than those in the C group. Further study showed that the effect of downhill treadmill running was partly blocked by compound C and strengthened by AICAR. A session of downhill treadmill running activated the AMPK pathway and promoted LC3 co-localizations with mitochondria and FKBP8, and induced mitophagy and mitochondrial damage within rat skeletal muscle.</p>\",\"PeriodicalId\":16779,\"journal\":{\"name\":\"Journal of physiology and biochemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-05-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of physiology and biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13105-025-01093-8\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of physiology and biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13105-025-01093-8","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Downhill running induced mitophagy in rat soleus muscle via the AMPK pathway.
Eccentric exercise is known to induce more pronounced muscle damage associated with delayed-onset muscle soreness than concentric exercise. This study aimed to investigate whether AMP-activated protein kinase (AMPK) pathway participates in control of mitophagy in rat skeletal muscle in response to downhill running. Eighty-eight male Sprague-Dawley rats were exercised on a treadmill tilted at 16° decline at 16 m·min- 1 for 90 min, with the soleus muscle sampled at 0 h, 12 h, 24 h, 48 h and 72 h after exercise. The AMPK inhibitor compound C or AMPK activator AICAR or saline was injected intraperitoneally 20 min before exercise. After downhill treadmill running, the skeletal muscle mitochondrial structure appeared to be abnormal and contained mitophagosomes; the expression levels of AMPK phosphorylation, cyclophilin D (CypD), cytochrome C (CytC), mitochondrial FK506-binding protein 8 (FKBP8), microtubule-associated protein 1 light chain 3 (LC3), and the co-localization of FKBP8 with LC3 and mitochondria with dynamin-related protein 1 (Drp1), lysosomal-associated membrane protein 2 (LAMP2) were significantly higher; the expression levels of mechanistic target of rapamycin (mTOR Ser2448) phosphorylation and heat shock protein 60 (HSP60), mitochondrial respiratory complex I (NDUFB8) and complex III (UQCRC2), and adenosine triphosphate (ATP) content were significantly lower than those in the C group. Further study showed that the effect of downhill treadmill running was partly blocked by compound C and strengthened by AICAR. A session of downhill treadmill running activated the AMPK pathway and promoted LC3 co-localizations with mitochondria and FKBP8, and induced mitophagy and mitochondrial damage within rat skeletal muscle.
期刊介绍:
The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.