Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Prostacyclin-dependent apoptosis mediated by PPAR delta.

T Hatae1, M Wada, C Yokoyama

  • 1Department of Pharmacology, National Cardiovascular Center Research Institute, Fujishiro-dai, Suita, Osaka 565-8565, Japan.

The Journal of Biological Chemistry
|September 12, 2001
PubMed
Summary

Intracellular prostacyclin (PGI(2)) promotes apoptosis by activating peroxisome proliferator-activated receptor delta (PPARδ). Extracellular PGI(2) and cAMP reduce apoptosis, revealing a novel signaling pathway for cell fate control.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway.

Journal of periodontal research·2015
Same author

A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B receptors underlying the antidepressant action of ketamine: a PET study with macaques.

Translational psychiatry·2014
Same author

Altered expression of dermokine in skin disorders.

Journal of the European Academy of Dermatology and Venereology : JEADV·2012
Same author

Induction of MMP-2 at the interface between epithelial cells and fibroblasts from human periodontal ligament.

Journal of periodontal research·2009
Same author

Mutual induction of noncollagenous bone proteins at the interface between epithelial cells and fibroblasts from human periodontal ligament.

Journal of periodontal research·2008
Same author

In vitro differentiation of epithelial cells cultured from human periodontal ligament.

Journal of periodontal research·2007

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostacyclin (PGI(2)) is a key regulator of hemostasis, acting as a vasodilator and inhibiting platelet aggregation.
  • PGI(2) exerts its canonical functions via the IP receptor, a G protein-coupled receptor that increases intracellular cyclic AMP (cAMP) levels.

Purpose of the Study:

  • To investigate the distinct roles of intracellular versus extracellular prostacyclin in cellular apoptosis.
  • To elucidate the signaling pathways involved in prostacyclin-mediated apoptosis, particularly the involvement of peroxisome proliferator-activated receptor delta (PPARδ).

Main Methods:

  • Expressing prostacyclin synthase in human embryonic kidney 293 cells to generate intracellular PGI(2).
  • Treating cells with extracellular PGI(2), dibutyryl cAMP, and the cAMP antagonist RpcAMP.

Related Experiment Videos

  • Utilizing a mutant form of PPARδ (L431A/G434A) to block receptor activation.

    • Main Results:

    • Intracellular PGI(2) significantly promoted apoptosis, mediated by the activation of endogenous PPARδ.
    • Extracellular PGI(2) and dibutyryl cAMP exhibited anti-apoptotic effects, reducing cell death.
    • The cAMP antagonist RpcAMP enhanced PGI(2)-induced apoptosis, suggesting a complex interplay between cAMP and PPARδ signaling.
    • Blocking PPARδ activation with a specific mutant abolished PGI(2)-mediated apoptosis.

    Conclusions:

    • Prostacyclin can activate a novel, PPARδ-dependent signaling pathway that promotes apoptosis, distinct from its canonical cAMP-mediated effects.
    • This discovery reveals a second, critical signaling role for prostacyclin in regulating cell fate.
    • Understanding this dual signaling capacity of PGI(2) opens new avenues for therapeutic interventions in diseases involving cell survival and death.