PMID- 9368689
OWN - NLM
STAT- MEDLINE
DCOM- 19971208
LR  - 20181113
IS  - 1355-008X (Print)
IS  - 1355-008X (Linking)
VI  - 6
IP  - 3
DP  - 1997 Jun
TI  - The effect of tumor necrosis factor-alpha and cAMP on induction of AP-1 activity 
      in MA-10 tumor Leydig cells.
PG  - 317-24
AB  - The immunostimulant tumor necrosis factor-alpha (TNF alpha), produced by 
      monocytes/macrophages in response to inflammatory disorders, regulates gene 
      expression in part through induction of mitogen-activated protein kinases 
      (MAPKs), including the stress-activated protein kinase (SAPK) (c-Jun N-terminal 
      kinase [JNK]) and the extracellular signal-regulated kinases (ERKs). In 
      testicular Leydig cells, the induction of steroidogenesis by cAMP is inhibited by 
      TNF alpha. To examine the potential mechanisms governing the mutual inhibition 
      between cAMP and TNF alpha in Leydig cells, the intracellular signaling pathways 
      that contribute to AP-1-dependent gene expression were examined in the mouse 
      MA-10 Leydig cell line. TNF alpha induced SAPK activity sixfold at 15 min, and 
      the PKC inhibitor calphostin C reduced the induction of SAPK by 30%. cAMP induced 
      SAPK activity twofold but reduced TNF alpha-induced SAPK activity. ERK activity 
      was inhibited by both cAMP and TNFa. TNFa increased c-Jun protein, but only 
      weakly induced FOS proteins (c-Fos, FosB, Fra-1, and Fra-2) whereas cAMP 
      increased the abundance of several FOS proteins (c-Fos, FosB, Fra-1, and Fra-2), 
      with little effect on c-Jun levels. AP-1 binding activity, assessed using 
      electrophoretic mobility shift assays, was increased twofold by TNF alpha and 
      fivefold by cAMP. Cyclic AMP alone induced AP-1-responsive reporter (p3TPLUX) 
      activity threefold after 2 h with peak effect of 4-fold at 4 hr. AP-1 reporter 
      was not induced by TNF alpha alone but in the presence of cAMP, TNF alpha induced 
      AP-1 reporter activity 12-fold. In conclusion, TNF alpha and cAMP induce distinct 
      components that separately contribute to the modulation of AP-1 activity in MA-10 
      cells.
FAU - Li, X
AU  - Li X
AD  - Department of Physiology & Biophysics, University of Illinois at Chicago 
      60612-7342, USA.
FAU - Hales, K H
AU  - Hales KH
FAU - Watanabe, G
AU  - Watanabe G
FAU - Lee, R J
AU  - Lee RJ
FAU - Pestell, R G
AU  - Pestell RG
FAU - Hales, D B
AU  - Hales DB
LA  - eng
GR  - 5 T32 GM0852-10/GM/NIGMS NIH HHS/United States
GR  - CA70896/CA/NCI NIH HHS/United States
GR  - HD27571/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Naphthalenes)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (calphostin complex)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/*metabolism
MH  - Cyclic AMP/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel/methods
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Genes, Reporter/drug effects
MH  - Leydig Cells/drug effects/enzymology/*metabolism
MH  - Male
MH  - Mice
MH  - Naphthalenes/pharmacology
MH  - Osmolar Concentration
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Proto-Oncogene Proteins c-fos/analysis/biosynthesis
MH  - Proto-Oncogene Proteins c-jun/analysis/biosynthesis
MH  - Rabbits
MH  - Time Factors
MH  - Transcription Factor AP-1/drug effects/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1997/06/01 00:00
MHDA- 1997/11/22 00:01
CRDT- 1997/06/01 00:00
PHST- 1997/06/01 00:00 [pubmed]
PHST- 1997/11/22 00:01 [medline]
PHST- 1997/06/01 00:00 [entrez]
AID - 10.1007/BF02820509 [doi]
PST - ppublish
SO  - Endocrine. 1997 Jun;6(3):317-24. doi: 10.1007/BF02820509.