Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Depletion of substrates f… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Depletion of substrates for protein prenylation increases apoptosis in human periovulatory granulosa cells

Artikel i vetenskaplig tidskrift
Författare Emilia Rung
P. Anders Friberg
Christina Bergh
Håkan Billig
Publicerad i Molecular reproduction and development
Volym 73
Nummer/häfte 10
Sidor 1277-83
ISSN 1040-452X (Print)
Publiceringsår 2006
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Institutionen för kliniska vetenskaper
Sidor 1277-83
Språk en
Länkar dx.doi.org/10.1002/mrd.20551
Ämnesord *Apoptosis/drug effects, Cells, Cultured, Cholesterol/*biosynthesis, Diterpenes/pharmacology, Estrenes/pharmacology, Farnesol/pharmacology, Farnesyltranstransferase/antagonists & inhibitors, Female, Furans/pharmacology, Granulosa Cells/drug effects/metabolism/*physiology, Hormone Antagonists/pharmacology, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology, Imidazoles/pharmacology, Leucine/analogs & derivatives/pharmacology, Mifepristone/pharmacology, Ovulation, Protein Isoprenylation/*drug effects, Quinolones/pharmacology, Receptors, Progesterone/antagonists & inhibitors
Ämneskategorier Medicin och Hälsovetenskap, Fysiologi

Sammanfattning

Progesterone receptor (PR) stimulation promotes survival in human and rat periovulatory granulosa cells. PR antagonists, Org 31710 and RU 486, both increase apoptosis and decrease cholesterol synthesis in these cells. The decrease in cholesterol synthesis also causes decreased synthesis of other products branching from the cholesterol synthesis pathway, including substrates for protein prenylation. In this study we focus on the link between apoptosis and prenylation in human periovulatory granulosa cells. A decreased cholesterol synthesis and increased apoptosis was verified in experiments with human periovulatory granulosa cells treated with the PR antagonists Org 31710 or RU 486 by measuring caspase-3/7 activity and incorporation of 14C-acetate into cholesterol and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory human granulosa cells using HMG-CoA reductase inhibitors (lovastatin or simvastatin) increased apoptosis, measured as caspase-3/7 activity. The increase in apoptosis caused by simvastatin or Org 31710 was partially reversed by addition of the protein prenylation precursors farnesol or geranylgeraniol. In addition, the prenylation inhibitors FTI R115777 and GGTI 2147 increased apoptosis in these cells. In conclusion our data suggest that PR antagonists increase apoptosis and reduce cholesterol synthesis in periovulatory granulosa cells and that the resulting depletion of substrates for protein prenylation may contribute to the increased apoptosis sensitivity.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?