Soluble Fas ligand activates the sphingomyelin pathway and induces apoptosis in luteal steroidogenic cells independently of stress-activated p38(MAPK)

James K Pru; Isabel R Hendry; John S Davis; Bo R Rueda

doi:10.1210/en.2002-220229

Back

Soluble Fas ligand activates the sphingomyelin pathway and induces apoptosis in luteal steroidogenic cells independently of stress-activated p38(MAPK)

Journal article

Open access

Peer reviewed

Soluble Fas ligand activates the sphingomyelin pathway and induces apoptosis in luteal steroidogenic cells independently of stress-activated p38(MAPK)

James K Pru, Isabel R Hendry, John S Davis and Bo R Rueda

Endocrinology (Philadelphia), Vol.143(11), pp.4350-4357

11/2002

DOI: https://doi.org/10.1210/en.2002-220229

Handle:

https://hdl.handle.net/2376/112833

PMID: 12399431

Files and links (1)

url

https://doi.org/10.1210/en.2002-220229View

Published (Version of record) Open

Abstract

Sphingomyelins - metabolism

Apoptosis - drug effects

Membrane Glycoproteins - pharmacology

Enzyme Inhibitors - pharmacology

Stress, Physiological

Enzyme Activation - drug effects

Blotting, Western

Ceramides - pharmacology

Fas Ligand Protein

Hydrolysis

Pregnancy

Corpus Luteum - cytology

Animals

Sphingomyelin Phosphodiesterase - antagonists & inhibitors

Cattle

Corpus Luteum - metabolism

Sphingomyelin Phosphodiesterase - metabolism

Female

Progesterone - biosynthesis

Steroids - biosynthesis

p38 Mitogen-Activated Protein Kinases

Mitogen-Activated Protein Kinases - metabolism

Fas ligand (FasL) is implicated as a mediator of luteolysis. However, a gap exists in our understanding of the Fas-mediated signaling mechanisms that are involved in either the loss of progesterone production or the structural regression of the corpus luteum. In the present study we investigated the acute and chronic effects of FasL with respect to activation of cytokine/stress-induced signaling pathways and apoptosis in bovine steroidogenic cells. More specifically, we investigated soluble FasL (sFasL)-activated production of ceramide, a second messenger of the sphingomyelin pathway, and activation of p38(MAPK), a member of the MAPK family. sFasL activated the sphingomyelin pathway, as evidenced by a 2-fold increase (P < 0.05) in the production of ceramide. Pretreatment with imipramine (50 micro M), an inhibitor of acid sphingomyelinase activity, attenuated (75%; P < 0.05) sFasL-induced ceramide production, suggesting that the increase in ceramide was partially the result of acid sphingomyelinase-mediated hydrolysis of sphingomyelin. Treatment of luteal cells with sFasL or a cell-permeable ceramide analog (C8) for 24-48 h resulted in a significant increase (P < 0.05) in apoptosis. Western blot analysis revealed that sFasL had little effect on the activation of p38(MAPK) in primary bovine luteal steroidogenic cells. Furthermore, pretreatment with the p38(MAPK) inhibitor SB203580 failed (P > 0.05) to inhibit sFasL- or C8-induced death. Although sFasL did not alter basal progesterone levels detected in the culture medium, C8 caused a significant increase (P < 0.05) in progesterone concentrations within the medium. Collectively, these data suggest that the role of FasL in luteolysis may be to activate the stress-induced sphingomyelin pathway that, in turn, serves as a mediator of apoptosis.

Metrics

6 Record Views

Details

Title: Soluble Fas ligand activates the sphingomyelin pathway and induces apoptosis in luteal steroidogenic cells independently of stress-activated p38(MAPK)
Creators: James K Pru - Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Isabel R Hendry
John S Davis
Bo R Rueda
Publication Details: Endocrinology (Philadelphia), Vol.143(11), pp.4350-4357
Academic Unit: Animal Sciences, Department of
Publisher: United States
Grant note: R01-HD-35934 / NICHD NIH HHS
Identifiers: 99900548072901842
Language: English
Resource Type: Journal article