PMID- 12606464
OWN - NLM
STAT- MEDLINE
DCOM- 20040116
LR  - 20121115
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 68
IP  - 4
DP  - 2003 Apr
TI  - Role of tumor necrosis factor-alpha and the modulating effect of the caspases in 
      rat corpus luteum apoptosis.
PG  - 1241-8
AB  - Tumor necrosis factor-alpha (TNFalpha) is a pleiotropic cytokine that has been 
      implicated in apoptosis of many cell systems. However, the signal transduction of 
      TNFalpha during the structural and functional regression of the corpus luteum 
      (CL) is largely unknown. In this study, we investigate the role of TNFalpha in 
      rat CL apoptosis and the involvement of monocyte chemoattractant protein-1 
      (MCP-1) and the modulating effect of the caspases in this process. An in vivo 
      study of CL during pregnancy and postpartum using immunohistochemistry and 
      Western blot analysis indicated that increases in TNFalpha correspond with luteal 
      apoptosis approaching term (Day 22) and at postpartum (Day 3). CL apoptosis was 
      further investigated using a whole-CL culture model of tropic withdrawal. An 
      increase was observed in both low molecular weight (MW) DNA fragmentation and 
      TUNEL staining from 0 h to 8 h in culture. CL apoptosis in vitro was associated 
      with increased protein expression of both TNFalpha and MCP-1 as measured by 
      immunohistochemistry and Western blot analysis. Using a whole-CL culture model, 
      apoptosis was induced in vitro by TNFalpha as demonstrated by a dose-dependent 
      increase in DNA fragmentation. Treatment of luteal cells with TNFalpha and both 
      specific caspase inhibitors (Z-DEVD-FMK, Z-VEID-FMK, Z-IETD-FMK) or a general 
      caspase inhibitor (Boc-D-FMK) prevented the effect of TNFalpha. CL regression 
      involves the apoptotic deletion of luteal cells; the results of this study 
      suggest that TNFalpha is possibly involved in this process. The observed 
      increases in MCP-1 expression suggest the coordination of TNFalpha expression 
      with the infiltration and activation of macrophages. Furthermore, the results 
      demonstrate the importance of the caspases in the TNFalpha signal transduction 
      pathway and suggest a hierarchy within the caspase family.
FAU - Abdo, Michael
AU  - Abdo M
AD  - School of Anatomy and Human Biology, The University of Western Australia, 
      Crawley, Western Australia 6009, Australia.
FAU - Hisheh, Susan
AU  - Hisheh S
FAU - Dharmarajan, Arun
AU  - Dharmarajan A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20021030
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Blotting, Western
MH  - Caspase Inhibitors
MH  - Caspases/*physiology
MH  - Chemokine CCL2/metabolism
MH  - Corpus Luteum/cytology/drug effects/metabolism/*physiology
MH  - Culture Techniques
MH  - DNA Fragmentation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - In Situ Nick-End Labeling
MH  - Pregnancy
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/administration & dosage/metabolism/*physiology
EDAT- 2003/02/28 04:00
MHDA- 2004/01/17 05:00
CRDT- 2003/02/28 04:00
PHST- 2003/02/28 04:00 [pubmed]
PHST- 2004/01/17 05:00 [medline]
PHST- 2003/02/28 04:00 [entrez]
AID - biolreprod.102.010819 [pii]
AID - 10.1095/biolreprod.102.010819 [doi]
PST - ppublish
SO  - Biol Reprod. 2003 Apr;68(4):1241-8. doi: 10.1095/biolreprod.102.010819. Epub 2002 
      Oct 30.