Ferroptosis in a sarcopenia model of senescence accelerated mouse prone 8 (SAMP8).
Ferroptosis in a sarcopenia model of senescence accelerated mouse prone 8 (SAMP8).
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DOI：
10.7150/ijbs.53126
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发表时间：
2021
影响因子：
9.2
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Huang Y;Wu B;Shen D;Chen J;Yu Z;Chen C
作为一种全身性综合征，其特征在于与年龄相关的退行性骨骼肌萎缩，肌肉减少症导致老年人不良结局的风险。在肌肉减少症动物模型和患者的肌肉中发现了与铁相关的铁积累，但铁在肌肉减少症中的作用仍然知之甚少。最近发现，在几种疾病中的铁过载与铁凋亡有关，铁凋亡是一种依赖铁的程序性细胞死亡形式。然而，这种过量的铁是否会导致肌肉中的铁下垂仍不清楚。在我们目前的研究中，我们发现柠檬酸铁诱导C2 C12细胞的铁凋亡，以及损害其分化成肌细胞肌管。由于肌肉质量和纤维尺寸的减少，使用40周龄的衰老加速型小鼠倾向8（SAMP 8）小鼠作为肌肉减少症模型，与8周龄的SAMP 8对照相比，发现其肌肉中的铁含量和铁细胞凋亡的标志物增加。此外，我们的研究结果表明，铁超载上调P53的表达，随后抑制Slc 7a 11（溶质载体家族7，成员11），一个已知的铁中毒相关基因的蛋白水平。Slc 7a 11的下调通过脂质过氧化产物的积累引起肌细胞的铁凋亡，这可能是肌肉减少症的原因之一。这项研究的结果表明，铁在触发P53-Slc 7a 11介导的肌肉铁凋亡中起着关键作用，并表明靶向铁积累和铁凋亡可能是治疗肌肉减少症的治疗策略。
As a systemic syndrome characterized by age-associated degenerative skeletal muscle atrophy, sarcopenia leads to a risk of adverse outcomes in the elderly. Age-related iron accumulation is found in the muscles of sarcopenia animal models and patients, but the role of iron in sarcopenia remains poorly understood. It has been recently found that iron overload in several diseases is involved in ferroptosis, an iron- dependent form of programmed cell death. However, whether this excess iron can result in ferroptosis in muscles is still unclear. In our present study, we found that ferric citrate induced ferroptosis in C2C12 cells, as well as impaired their differentiation from myoblasts to myotubes. Due to the decreased muscle mass and fiber size, 40-week-old senescence accelerated mouse prone 8 (SAMP8) mice were used as a sarcopenia model, in whose muscles the iron content and markers of ferroptosis were found to increase, compared to 8-week- old SAMP8 controls. Moreover, our results showed that iron overload upregulated the expression of P53, which subsequently repressed the protein level of Slc7a11 (solute carrier family 7, member 11), a known ferroptosis-related gene. The downregulation of Slc7a11 then induced the ferroptosis of muscle cells through the accumulation of lipid peroxidation products, which may be one of the causes of sarcopenia. The findings in this study indicate that iron plays a key role in triggering P53- Slc7a11-mediated ferroptosis in muscles, and suggest that targeting iron accumulation and ferroptosis might be a therapeutic strategy for treating sarcopenia.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
25.7
作者：
Wang, GS;Eriksson, LC;Stål, P
通讯作者：
Stål, P
DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan
影响因子：
3.4
作者：
Altun, Mikael;Edstrom, Erik;Ulfhake, Brun
通讯作者：
Ulfhake, Brun
DOI：
10.1067/mlc.2001.113504
发表时间：
2001-04-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Morley, JE;Baumgartner, RN;Nair, KS
通讯作者：
Nair, KS