Long-term physical inactivity exacerbates hindlimb unloading-induced muscle atrophy in young rat soleus muscle
Long-term physical inactivity exacerbates hindlimb unloading-induced muscle atrophy in young rat soleus muscle
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DOI：
10.1152/japplphysiol.00494.2020
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发表时间：
2021-04-01
影响因子：
3.3
通讯作者：
Naito, Hisashi
中科院分区：
文献类型：
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作者：
Yoshihara, Toshinori;Natsume, Toshiharu;Naito, Hisashi
本研究旨在探讨青少年长期缺乏运动对大鼠比目鱼肌随后后肢去负荷引起的肌肉萎缩的影响。首先，将3周龄雄性Wistar大鼠分配到年龄匹配的对照组（n = 6）或体力活动不足组（n = 8）。运动不活跃组的大鼠被关在狭窄的笼子里，笼子的面积大约是通常面积的一半，持续8周以限制运动范围。测量全身能量消耗，并去除血液、器官、股骨和后肢肌肉。我们发现，长期缺乏体力活动不会影响生长期大鼠的代谢和生理特征。将五十六只3周龄雄性Wistar大鼠随机分为对照组（n = 28）和运动不活动组（n = 28）。8 wk后，两组大鼠均行后肢去负荷。在卸载前（0天）和卸载后1、3和7天（每组n = 7）取出比目鱼肌。虽然两组的比目鱼肌重量在后肢去负荷7天后均显著降低，但非活动组的降低幅度较大。根据4-羟基壬烯醛结合蛋白水平和组蛋白脱乙酰酶4（HDAC 4）和NF-κ B蛋白水平，观察到不活动和卸载之间的显著相互作用（P < 0.01）。运动不活动组HDAC 4和NF-κ B p65蛋白水平在后肢去负荷后1天显著增加，沿着增加的还有其下游靶基因肌生成素和肌肉环指蛋白1（MuRF 1）的mRNA水平。长期的体力活动不活动会加剧后肢卸载诱导的年轻大鼠比目鱼肌废用性肌肉萎缩，这可能是通过HDAC 4和NF-κ B p65诱导的MuRF 1 mRNA上调介导的氧化应激诱导的蛋白泛素化。
This study investigated the effects of long-term physical inactivity in adolescent on subsequent hindlimb unloading-induced muscle atrophy in rat soleus muscle. First, 3-wk-old male Wistar rats were assigned to an age-matched control (n = 6) or a physical inactivity (n = 8) group. Rats in the physical inactivity group were housed in narrow cages with approximately half the usual floor space for 8 wk to limit range of movement. Whole body energy consumption was measured, and the blood, organs, femoral bone, and hindlimb muscles were removed. We found that long-term physical inactivity did not affect the metabolic and physiological characteristics of growing rats. Then, fifty-six 3-wk-old male Wistar rats were assigned randomly into control (n = 28) and physical inactivity (n = 28) groups. After 8 wk, the rats in both groups underwent hindlimb unloading. The soleus muscles were removed before unloading (0 day), and 1, 3, and 7 days after unloading (n = 7 for each). Although the soleus muscle weight was significantly decreased after 7 days of hindlimb unloading in both groups, the decrease was drastic in the inactive group. A significant interaction between inactivity and unloading (P < 0.01) was observed according to the 4-hydroxynonenal-conjugated protein levels and the histone deacetylase 4 (HDAC4) and NF-kappa B protein levels. HDAC4 and NF-kappa B p65 protein levels in the physical inactivity group increased significantly 1 day after hindlimb unloading, along with the mRNA levels of their downstream targets myogenin and muscle RING finger protein 1 (MuRF1). Subsequent protein ubiquitination was upregulated by long-term physical inactivity (P < 0.05).NEW & NOTEWORTHY Long-term physical inactivity exacerbates hindlimb unloading-induced disuse muscle atrophy in young rat soleus muscles, possibly mediated by oxidative stress-induced protein ubiquitination via HDAC4- and NF-kappa B p65-induced MuRF1 mRNA upregulation.