Protein kinase Cδ contributes to phenylephrine-mediated contraction in the aortae of high fat diet-induced obese mice

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Limei Liu
  • Jian Liu
  • Yuansheng Gao
  • Xiaoxing Yu
  • Dou Dou

Detail(s)

Original languageEnglish
Pages (from-to)1179-1183
Journal / PublicationBiochemical and Biophysical Research Communications
Volume446
Issue number4
Publication statusPublished - 18 Apr 2014
Externally publishedYes

Abstract

The down-regulation of α-adrenoceptor-mediated signaling casacade has been implicated in obesity but the underlying mechanism remains largely unknown the present study investigated whether inositol 1,4,5-trisphosphate (IP3) receptor and protein kinase C (PKC) were involved in the reduction of α1-adrenoceptor agonist phenylephrine-evoked contraction in aortae of high fat diet-induced obese (DIO) mice. C57BL/6 mice were fed with a rodent diet containing 45 kcal% fat for 16 weeks to induce obesity. Isolated mouse aortae were suspended in myograph for isometric force measurement. Protein phosphorylations and expressions were determined by Western blotting. In C57BL/6 mouse aortae, phenylephrine-induced contraction was partially inhibited by either IP3 receptor antagonist heparin or PKC inhibitor GFX, and the combined treatment with heparin and GFX abolished the contraction. Phenylephrine-induced contraction was significantly less in the aortae of DIO mice than those of control mice; only GFX but not heparin attenuated the contraction, indicating a diminishing role of IP3 receptor in DIO mice. Western blotting showed the reduced expression and phosphorylation of IP3 receptor and the down-regulated expression of PKC, PKCβ, PKCδ, and PKCζ in DIO mouse aortae. Importantly, PKCδ was more likely to maintain phenylephrine-mediated contraction in DIO mouse aortae because that (1) PKCδ inhibitor rottlerin but not PKCα and PKCβ inhibitor Gö6976, PKCβ inhibitor hispidin, or PKCζ pseudosubstrate inhibitor attenuated the contraction; and (2) PKCδ phosphorylation was increased but phosphorylations of PKCα, PKCβ, and PKCζ were reduced in DIO mouse aortae the present study thus provides additional insights into the cellular mechanisms responsible for vascular dysfunction in obesity. © 2014 Elsevier Inc. All rights reserved.

Research Area(s)

  • Aorta, Inositol 1,4,5-trisphosphate (IP3) receptor, Obesity, Protein kinase C, α-Adrenoceptor

Bibliographic Note

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Citation Format(s)

Protein kinase Cδ contributes to phenylephrine-mediated contraction in the aortae of high fat diet-induced obese mice. / Liu, Limei; Liu, Jian; Gao, Yuansheng; Yu, Xiaoxing; Dou, Dou; Huang, Yu.

In: Biochemical and Biophysical Research Communications, Vol. 446, No. 4, 18.04.2014, p. 1179-1183.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review