Lipoprotein(a) [Lp(a)] is a strong

Lipoprotein(a) [Lp(a)] is a strong genetic risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Hydrogen sulfide (H2 S), a member of the gas transmitter family, performs important biological actions, including protection against cardiovascular diseases and maintenance of the lipid metabolism equilibrium in hepatocytes and adipocytes. In this study, we investigated the possible molecular mechanism of H2 S that influences apolipoprotein(a) [apo(a)] biosynthesis. We also determined the effects of H2 S on apo(a) expression and secretion in HepG2 cells as well as the underlying mechanisms. Results showed that H2 S significantly inhibited the expression and secretion levels of apo(a). These effects were attenuated by the PKCα inhibitor and FXR siRNA. H2 S also reduced HNF4α expression and enhanced FXR expression. The Akt inhibitor partially reversed H2 S-induced inhibition of apo(a) and HNF4α expression and apo(a) secretion. This study reveals that H2 S suppressed apo(a) expression and secretion via the PKCα-FXR and PI3K/Akt-HNF4α pathways.
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ผลลัพธ์ (แอฟริกา) 1:

Lipoproteïen (a) [Lp (a)] is 'n sterk genetiese risikofaktor vir koronêre hartsiektes. Bly egter die metabolisme van hierdie proteïen swak verstaan. Doeltreffende en spesifieke middels wat 'n hoë plasmavlakke van Lp (a) kan daal nog nie ontwikkel. Waterstofsulfied (H2 S), 'n lid van die gas sender gesin, voer belangrike biologiese aksies, insluitende beskerming teen kardiovaskulêre siektes en instandhouding van die lipiedmetabolisme ewewig in hepatosiete en Adiposiete. In hierdie studie ondersoek ons die moontlike molekulêre meganisme van H2 S wat apolipoproteïen (a) [apo (a)] biosintese beïnvloed. Ons het ook bepaal die uitwerking van H2 S op apo (a) uitdrukking en sekresie in HepG2 selle sowel as die onderliggende meganismes. Resultate het getoon dat H2 S aansienlik geïnhibeer die uitdrukking en afskeiding vlakke van apo (a). Hierdie effekte is verswakte deur die PKCα inhibeerder en FXR siRNA. H2 S ook verminder HNF4α uitdrukking en verbeterde FXR uitdrukking. Die Akt inhibeerder gedeeltelik omgekeer H2 S-geïnduseerde inhibisie van apo (a) en HNF4α uitdrukking en apo (a) afskeiding. Studie toon dat hierdie H2 S onderdruk APO (a) Expression en afskeiding via die FXR-PKCα en PI3K / Akt paaie-HNF4α.
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