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HDAC5-mTORC1 Interaction in Differential Regulation of Ghrelin and Nucleobindin 2 (NUCB2)/Nesfatin-1.
Ma, Liangxiao; Tang, Hong; Yin, Yue; Yu, Ruili; Zhao, Jing; Li, Yin; Mulholland, Michael W; Zhang, Weizhen.
Affiliation
  • Ma L; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Tang H; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Yin Y; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Yu R; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Zhao J; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Li Y; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Mulholland MW; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
  • Zhang W; Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China; and Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346.
Mol Endocrinol ; 29(11): 1571-80, 2015 Nov.
Article in En | MEDLINE | ID: mdl-26357899
ABSTRACT
Sodium valporate (VPA), a broad-spectrum inhibitor of histone deacetylases (HDACs), increased ghrelin whereas decreased nesfatin-1 in mice fed normal chow diet or high-fat diet. Alterations in ghrelin and nucleobindin 2/nesfatin-1 were mediated by HDAC5 but not HDAC4. Activation of mTORC1 significantly attenuated the effect of VPA on ghrelin and nesfatin-1 levels. HDAC5 coimmunoprecipitated with raptor. Inhibition of HDAC5 by VPA, trichostatin A, or siHDAC5 markedly increased acetylation of raptor Lys840 and subsequent phosphorylation of raptor Ser792, resulting in suppression of mTORC1 signaling. A raptor mutant lacking the Lys840 acetylation site showed a decrement in phosphorylation of raptor Ser792 and subsequent increase in mTORC1 signaling. These alterations were associated with reciprocal changes in ghrelin and nucleobindin 2/nesfatin-1 expression. These findings reveal HDAC5-mTORC1 signaling as a novel mechanism in the differential regulation of gastric ghrelin and nesfatin-1.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium-Binding Proteins / Multiprotein Complexes / Adaptor Proteins, Signal Transducing / DNA-Binding Proteins / Ghrelin / TOR Serine-Threonine Kinases / Histone Deacetylases / Nerve Tissue Proteins Limits: Animals Language: En Journal: Mol Endocrinol Journal subject: BIOLOGIA MOLECULAR / ENDOCRINOLOGIA Year: 2015 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium-Binding Proteins / Multiprotein Complexes / Adaptor Proteins, Signal Transducing / DNA-Binding Proteins / Ghrelin / TOR Serine-Threonine Kinases / Histone Deacetylases / Nerve Tissue Proteins Limits: Animals Language: En Journal: Mol Endocrinol Journal subject: BIOLOGIA MOLECULAR / ENDOCRINOLOGIA Year: 2015 Document type: Article