SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals

被引：36

作者：

Akieda-Asai, Sayaka ^{[1
,2
]}

Zaima, Nobuhiro ^{[2
,3
]}

Ikegami, Koji ^{[2
,3
]}

Kahyo, Tomoaki ^{[2
,4
]}

Yao, Ikuko ^{[2
,5
]}

Hatanaka, Takahiro ^{[2
]}

Iemura, Shun-ichiro ^{[6
]}

Sugiyama, Rika ^{[7
,8
]}

Yokozeki, Takeaki ^{[7
,8
]}

Eishi, Yoshinobu ^{[9
]}

Koike, Morio ^{[9
]}

Ikeda, Kyoji ^{[10
]}

Chiba, Takuya ^{[11
]}

Yamaza, Haruyoshi ^{[11
,12
]}

Shimokawa, Isao ^{[11
]}

Song, Si-Young ^{[2
]}

Matsuno, Akira ^{[13
]}

Mizutani, Akiko ^{[14
]}

Sawabe, Motoji ^{[15
,16
,17
]}

Chao, Moses V. ^{[18
]}

Tanaka, Masashi ^{[19
]}

Kanaho, Yasunori ^{[7
,8
]}

Natsume, Tohru ^{[6
]}

Sugimura, Haruhiko ^{[4
]}

Date, Yukari ^{[1
]}

McBurney, Michael W. ^{[20
,21
]}

Guarente, Leonard ^{[22
]}

Setou, Mitsutoshi ^{[2
,3
]}

机构：

[1] Miyazaki Univ, Frontier Sci Res Ctr, Miyazaki, Japan

[2] Mitsubishi Kagaku Inst Life Sci, Tokyo, Japan

[3] Hamamatsu Univ Sch Med, Dept Mol Anat, Shizuoka, Japan

[4] Hamamatsu Univ Sch Med, Dept Pathol, Shizuoka, Japan

[5] Kansai Med Univ, Dept Med Chem, Osaka, Japan

[6] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Tokyo, Japan

[7] Univ Tsukuba, Dept Physiol Chem, Grad Sch Comprehens Human Sci, Ibaraki, Japan

[8] Univ Tsukuba, Inst Basic Med Sci, Ibaraki, Japan

[9] Tokyo Med & Dent Univ, Dept Human Pathol, Tokyo, Japan

[10] Natl Ctr Geriatr & Gerontol, Dept Bone & Joint Dis, Res Inst, Aichi, Japan

[11] Nagasaki Univ, Grad Sch Biomed Sci, Dept Investigat Pathol, Nagasaki 852, Japan

[12] Kyushu Univ, Sect Pediat Dent, Div Oral Hlth Growth & Dev, Fac Dent Sci, Fukuoka 812, Japan

[13] Teikyo Univ Chica Med Ctr, Dept Neurosurg, Chiba, Japan

[14] Tokai Univ, Sch Med, Hiratsuka, Kanagawa 25912, Japan

[15] Tokyo Metropolitan Geriatr Hosp, Dept Pathol, Tokyo 173, Japan

[16] Tokyo Metropolitan Geriatr Hosp, Bioresource Ctr Geriatr Res, Tokyo 173, Japan

[17] Inst Gerontol, Tokyo, Japan

[18] NYU, Sch Med, Mol Neurobiol Program, Skirball Inst Biomol Med, New York, NY USA

[19] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan

[20] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada

[21] Univ Ottawa, Dept Med, Ottawa, ON, Canada

[22] MIT, Dept Biol, Cambridge, MA USA

来源：

PLOS ONE | 2010年 / 5卷 / 07期

关键词：

PHOSPHATIDYLINOSITOL; 4-PHOSPHATE; 5-KINASE; CALORIE RESTRICTION; INSULIN SENSITIVITY; LONGEVITY PROTEIN; INCREASED DOSAGE; LIFE-SPAN; GH3; CELL; RECEPTOR; THYROTROPIN; MICE;

D O I：

10.1371/journal.pone.0011755

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: 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. Methodology/Principal Findings: 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) c was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5K gamma and enhanced PIP5K gamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5K gamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5K gamma, PI(4,5) P-2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance: Our findings indicated that the control of TSH release by the SIRT1-PIP5K gamma pathway is important for regulating the metabolism of the whole body.

引用

页数：12

共 72 条

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