Depletion of ubiA prenyltransferase domain containing 1 expression promotes angiotensin II‑induced hypertrophic response in AC16 human myocardial cells via modulating the expression levels of coenzyme Q10 and endothelial nitric oxide synthase

Mol Med Rep. 2017 Nov;16(5):6910-6915. doi: 10.3892/mmr.2017.7407. Epub 2017 Aug 31.

Abstract

UbiA prenyltransferase domain containing 1 (UBIAD1) is closely associated with cardiovascular diseases. However, at the cellular level, little is known about how UBIAD1 is expressed and functions in cardiomyocyte hypertrophy. The aim of the present study was to investigate the expression and role of UBIAD1 in angiotensin II (Ang II)‑induced hypertrophy in AC16 cardiomyoblast cells. The loss‑of‑function approach was used to knock down UBIAD1 in vehicle‑ and Ang II‑stimulated AC16 cells. The levels of atrial natriuretic factor (ANF) and caspase-3 were measured and compared between vehicle‑ and Ang II‑treated AC16 cells pretreated with control siRNA or siRNA against UBIAD1. In addition, the levels of coenzyme Q10 (CoQ10) and endothelial nitric oxide synthase (eNOS) were evaluated and compared between these groups. Ang II induced hypertrophy and apoptosis in AC16 cells, accompanied by increased expression of ANF and caspase-3, and decreased expression of UBIAD1. These effects were potentiated by UBIAD1 knockdown. In addition, Ang II treatment suppressed the expression of CoQ10 and eNOS, as well as the production of NO, and these inhibitory effects were also enhanced by UBIAD1 knockdown. Thus, silencing of UBIAD1 expression promotes a myocardial hypertrophic response to Ang II stimulation, in part, by suppressing the expression of CoQ10 and eNOS.

MeSH terms

  • Angiotensin II / pharmacology*
  • Apoptosis / drug effects
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line
  • Dimethylallyltranstransferase / antagonists & inhibitors
  • Dimethylallyltranstransferase / deficiency
  • Dimethylallyltranstransferase / metabolism*
  • Gene Expression / drug effects*
  • Humans
  • Hypertrophy / etiology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / genetics
  • Ubiquinone / metabolism

Substances

  • RNA, Small Interfering
  • Angiotensin II
  • Ubiquinone
  • Nitric Oxide
  • Atrial Natriuretic Factor
  • Nitric Oxide Synthase Type III
  • Dimethylallyltranstransferase
  • UBIAD1 protein, human
  • Caspase 3
  • coenzyme Q10