PMID- 9316456
OWN - NLM
STAT- MEDLINE
DCOM- 19971023
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 273
IP  - 3 Pt 1
DP  - 1997 Sep
TI  - Inhibition of TSH-induced hydrogen peroxide production by TNF-alpha through a 
      sphingomyelinase signaling pathway.
PG  - E639-43
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be related to the 
      pathogenesis of autoimmune thyroid diseases, nonthyroid illness, and other 
      thyroid dysfunctions induced by infectious diseases. In relation to these, in 
      vitro studies demonstrated that TNF-alpha influences growth and/or differentiated 
      functions mediated by thyroid-stimulating hormone (TSH), including 125I 
      organification. In the present study, we found that TNF-alpha inhibits 
      TSH-induced H2O2 production, which is an inevitable process for iodide 
      organification, and hence thyroid hormone synthesis, in FRTL-5 thyroid cells. In 
      the cells, TNF-alpha induced ceramide production and the addition of exogenous 
      ceramide or sphingomyelinase treatment of the cells simulated TNF-alpha actions. 
      Although TSH stimulation of H2O2 production is mediated by the phospholipase C 
      (PLC)-Ca2+ pathway, TNF-alpha and exogenous and endogenous ceramide affected 
      neither TSH-dependent PLC activation and Ca2+ mobilization nor TSH-induced cAMP 
      accumulation but attenuated Ca(2+)-induced H2O2 production. We conclude that 
      TNF-alpha, through a sphingomyelinase-ceramide pathway, regulates TSH-induced 
      H2O2 production at steps beyond the Ca2+ mobilization step in the PLC-Ca2+ 
      signaling pathway coupled to TSH. This suggests participation of TNF-alpha in 
      thyroid disorder in hormone synthesis induced by thyroid disease associated with 
      the activation of immune systems.
FAU - Kimura, T
AU  - Kimura T
AD  - Laboratory of Signal Transduction, School of Medicine, Gunma University, 
      Maebashi, Japan.
FAU - Okajima, F
AU  - Okajima F
FAU - Kikuchi, T
AU  - Kikuchi T
FAU - Kuwabara, A
AU  - Kuwabara A
FAU - Tomura, H
AU  - Tomura H
FAU - Sho, K
AU  - Sho K
FAU - Kobayashi, I
AU  - Kobayashi I
FAU - Kondo, Y
AU  - Kondo Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (N-acetylsphingosine)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 56092-81-0 (Ionomycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9002-71-5 (Thyrotropin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Hydrogen Peroxide/*metabolism
MH  - Ionomycin/pharmacology
MH  - Kinetics
MH  - Sphingomyelin Phosphodiesterase/*metabolism
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Thyroid Gland/*physiology
MH  - Thyrotropin/antagonists & inhibitors/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1997/10/08 00:00
MHDA- 1997/10/08 00:01
CRDT- 1997/10/08 00:00
PHST- 1997/10/08 00:00 [pubmed]
PHST- 1997/10/08 00:01 [medline]
PHST- 1997/10/08 00:00 [entrez]
AID - 10.1152/ajpendo.1997.273.3.E638 [doi]
PST - ppublish
SO  - Am J Physiol. 1997 Sep;273(3 Pt 1):E639-43. doi: 10.1152/ajpendo.1997.273.3.E638.