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H2 S inhibits apo(a) expression and secretion through PKCα/FXR and Akt/HNF4α pathways in HepG2 cells

Kai Qu1, Ya-Mi Liu1, Xing-Lan He1

  • 1Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.

Cell Biology International
|June 15, 2016
PubMed

Insights

Hydrogen sulfide (H2S) significantly reduces apolipoprotein(a) [apo(a)] expression and secretion. This gas transmitter impacts lipid metabolism via PKCα-FXR and PI3K/Akt-HNF4α pathways, offering potential cardiovascular disease therapeutic strategies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cardiovascular Science

Background:

  • Lipoprotein(a) [Lp(a)] is a key genetic risk factor for coronary heart disease.
  • Understanding Lp(a) metabolism and developing drugs to lower its plasma levels are critical unmet needs.
  • Hydrogen sulfide (H2S) is recognized for its cardioprotective effects and role in lipid metabolism.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which H2S influences apolipoprotein(a) [apo(a)] biosynthesis.
  • To determine the effects of H2S on apo(a) expression and secretion in HepG2 cells.
  • To identify the signaling pathways involved in H2S-mediated regulation of apo(a).

Main Methods:

  • Investigated H2S effects on apo(a) expression and secretion in HepG2 cells.
  • Utilized PKCα inhibitor and FXR siRNA to probe signaling pathways.
  • Assessed the impact of H2S on HNF4α and FXR expression.
  • Employed Akt inhibitor to evaluate the PI3K/Akt pathway involvement.

Main Results:

  • H2S significantly inhibited apo(a) expression and secretion in HepG2 cells.
  • PKCα inhibition and FXR knockdown attenuated the effects of H2S on apo(a).
  • H2S reduced HNF4α expression and increased FXR expression.
  • Akt inhibition partially reversed H2S-induced inhibition of apo(a) and HNF4α expression and secretion.

Conclusions:

  • H2S suppresses apo(a) biosynthesis and secretion through distinct molecular pathways.
  • The PKCα-FXR pathway is implicated in H2S-mediated regulation of apo(a).
  • The PI3K/Akt-HNF4α pathway also plays a role in H2S's inhibitory effects on apo(a).
Keywords:
apolipoprotein(a)farnesoid X receptorhepG2 cellhepatocyte nuclear factor 4αhydrogen sulfidelipoprotein (a)

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