SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.
SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.
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DOI：
10.1371/journal.pone.0011755
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发表时间：
2010-07-23
期刊：
影响因子：
3.7
通讯作者：
Setou M
中科院分区：
文献类型：
--
作者：
Akieda-Asai S;Zaima N;Ikegami K;Kahyo T;Yao I;Hatanaka T;Iemura S;Sugiyama R;Yokozeki T;Eishi Y;Koike M;Ikeda K;Chiba T;Yamaza H;Shimokawa I;Song SY;Matsuno A;Mizutani A;Sawabe M;Chao MV;Tanaka M;Kanaho Y;Natsume T;Sugimura H;Date Y;McBurney MW;Guarente L;Setou M
SIRT 1是一种NAD依赖性脱乙酰酶，在多种器官中具有多种功能，如调节内分泌功能和代谢。然而，它如何调节那里的激素释放仍有待解决。在这里，我们报告说，SIRT 1在垂体促甲状腺激素细胞中大量表达，并调节甲状腺激素的分泌。SIRT 1水平的操纵显示，SIRT 1正调控含TSH颗粒的胞吐。使用基于LC/MS的相互作用组学，磷脂酰肌醇-4-磷酸5-激酶（PIP 5 K）γ被鉴定为SIRT 1结合伴侣和脱乙酰化底物。SIRT 1可使PIP 5 K γ中的两个特异性赖氨酸残基（K265/K268）脱乙酰化，并增强PIP 5 K γ酶活性。SIRT 1介导的TSH分泌被PIP 5 K γ敲低所消除。SIRT 1基因敲低可降低垂体细胞中去乙酰化PIP 5 K γ、PI（4，5）P2的水平，减少垂体细胞分泌TSH。这些结果也在SIRT 1敲除小鼠中观察到。我们的研究结果表明，通过SIRT 1-PIP 5 K γ途径控制TSH的释放对于调节全身代谢是重要的。
SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ and enhanced PIP5Kγ enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body.
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影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
影响因子：
10.5
作者：
Cohen, Dena E.;Supinski, Andrea M.;Guarente, Leonard P.
通讯作者：
Guarente, Leonard P.
影响因子：
4.8
作者：
Castellino, AM;Parker, GJ;Chao, MV
通讯作者：
Chao, MV
DOI：
10.18632/aging.100056
发表时间：
2009-06-03
期刊：
Aging
影响因子：
--
作者：
Armour SM;Baur JA;Hsieh SN;Land-Bracha A;Thomas SM;Sinclair DA
通讯作者：
Sinclair DA
DOI：
10.18632/aging.100028
发表时间：
2009-03-02
期刊：
Aging
影响因子：
--
作者：
Allison SJ;Jiang M;Milner J
通讯作者：
Milner J