Decreased SIRT1 deacetylase activity in sporadic inclusion-body myositis muscle fibers
Decreased SIRT1 deacetylase activity in sporadic inclusion-body myositis muscle fibers
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DOI：
10.1016/j.neurobiolaging.2008.08.021
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发表时间：
2010-09-01
影响因子：
4.2
通讯作者：
Askanas, Valerie
中科院分区：
文献类型：
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作者：
Nogalska, Anna;D'Agostino, Carla;Askanas, Valerie
SIRT1 属于 NAD(+) 依赖性组蛋白/蛋白质脱乙酰酶 Sirtum 家族。实验表明，SIRT1 活性增加可促进热量限制寿命，并减少 NF-κ B 激活和淀粉样蛋白 -β (A beta) 的量。我们研究了 SIRT1 在与衰老相关的肌肉疾病中的作用。散发性包涵体肌炎 (s-IBM)，其肌纤维中 NF-κ B 激活增加，Aβ 异常积累。我们证明了这一点。与年龄匹配的对照组相比，s-IBM 肌纤维 (1) SIRT1 活性和 SIRT1 靶标、H4、NF-kappa B 和 p53 的去乙酰化降低。 (2)SIRT1 mRNA和蛋白显着增加；(3)在细胞质中，SIRT1蛋白以细胞质聚集体的形式积累； (4)在细胞核中，SIRT1蛋白减少据我们所知，这是在与衰老相关的人类疾病中首次证明SIRT1异常，包括SIRT1脱乙酰酶活性降低，我们建议在s-IBM肌纤维中。 SIRT1 活性不足可能会因增加而有害。 NF-kappa B 激活并导致异常 A beta 积累。通过使用已知的 SIRT1 激活剂治疗来改善 SIRT1 的作用可能会使 s-IBM 患者受益。 (C) 2008 爱思唯尔公司保留所有权利
SIRT1 belongs to the sirtum family of NAD(+)-dependent histone/protem deacetylases Experimentally, increased activity of SIRT1 facilitates calorie-restricted longevity, and decreases NF-kappa B activation and the amount of the amyloid-beta (A beta). We studied SIRT1 in an aging-associated muscle disease. sporadic inclusion-body myositis (s-IBM), whose muscle fibers contain increased NF-kappa B activation and abnormal accumulation of A beta. We show that. as compared to the age-matched controls, in s-IBM muscle fibers (1) SIRT1 activity and dcacetylation of SIRT1 targets, H4, NF-kappa B and p53 were decreased. (2) SIRT1 mRNA and protein were significantly increased, (3) in the cytoplasm, SIRT1 protein was accumulated in the form of cytoplasmic aggregates; (4) in the nuclei, SIRT1 protein was decreasedTo our knowledge, this is the first demonstration of SIRT1 abnormalities, including decreased SIRT1 deacetylase activity, in human disease associated with aging We propose that in s-IBM muscle fibers. inadequate activity of SIRT1 may be detrimental by increasing. NF-kappa B activation and contributing to abnormal A beta accumulation. Improving SIRT1 action by treatment with known SIRT1 activators might benefit s-IBM patients. (C) 2008 Elsevier Inc All rights reserved