PKCβ/NF-κB pathway in diabetic atrial remodeling

Haili Wang, Yuanyuan Xu, Aiqing Xu, Xinghua Wang, Lijun Cheng, Sharen Lee, Gary Tse, Guangping Li, Tong Liu, Huaying Fu

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Atrial remodeling in diabetes is partially attributed to NF-κB/TGF-β signal transduction pathway activation. We examined whether the hyperglycemia-induced increased expression of NF-κB/TGF-β was dependent upon protein kinase C-β (PKCβ) and tested the hypothesis that selective inhibition of PKCβ using ruboxistaurin (RBX) can reduce NF-κB/TGF-β expression and inhibit abnormal atrial remodeling in streptozotocin (STZ)–induced diabetic rats. The effects of PKCβ inhibition on NF-κB/TGF-β signal transduction pathway-mediated atrial remodeling were investigated in STZ-induced diabetic rats. Mouse atrial cardiomyocytes (HL-1 cells) were cultured in low- or high-glucose or mannitol conditions in the presence or absence of small interference RNA that targeted PKCβ. PKCβ inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-κBp65, p-IκB, P38MARK, TNF-α, TGF-β, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats. Exposure of cardiomyocytes to high-glucose condition activated PKCβ and increased NF-κB/TGF-β expression. Suppression of PKCβ expression by small interference RNA decreased high-glucose–induced NF-κB and extracellular signal–related kinase activation in HL-1 cells. Pharmacological inhibition of PKCβ is an effective method to reduce AF incidence in diabetic rat models by preventing NF-κB/TGF-β-mediated atrial remodeling.

Original languageEnglish
Pages (from-to)637-653
Number of pages17
JournalJournal of Physiology and Biochemistry
Volume76
Issue number4
DOIs
Publication statusPublished - Nov 2020
Externally publishedYes

Keywords

  • Atrial fibrillation
  • Diabetes mellitus
  • Protein kinase C beta (PKCβ)
  • Remodeling

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