PMID- 11350760
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 280
IP  - 6
DP  - 2001 Jun
TI  - Tumor necrosis factor-alpha inhibits store-mediated Ca2+ entry in the human 
      hepatocellular carcinoma cell line HepG2.
PG  - C1636-44
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important component of the early 
      signaling pathways leading to liver regeneration and proliferation, but it is 
      also responsible for several hepatotoxic effects. We have investigated the effect 
      of TNF-alpha on thapsigargin (TG)-induced store-mediated Ca2+ entry (SMCE) in the 
      human hepatocellular carcinoma cell line HepG2. In these cells, short-term (10 
      min) exposure to TNF-alpha slightly increased SMCE. In contrast, long-term (12 h) 
      exposure to TNF-alpha significantly reduced SMCE. This effect was reversed by 
      coincubation with atrial natriuretic peptide (ANP), which itself had no effect on 
      SMCE. Cytochalasin D and latrunculin A, inhibitors of actin polymerization, 
      abolished SMCE. Long-term exposure of HepG2 cells to TNF-alpha abolished 
      TG-induced actin polymerization and membrane association of Ras proteins. When 
      TNF-alpha was added in combination with ANP, these effects were reduced. These 
      findings suggest that in HepG2 cells, TNF-alpha inhibits SMCE by affecting 
      reorganization of the actin cytoskeleton, probably by interfering with the 
      activation of Ras proteins, and that ANP protects against these inhibitory 
      effects of TNF-alpha.
FAU - Rosado, J A
AU  - Rosado JA
AD  - Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United 
      Kingdom.
FAU - Rosenzweig, I
AU  - Rosenzweig I
FAU - Harding, S
AU  - Harding S
FAU - Sage, S O
AU  - Sage SO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Actins)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Carcinogens)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (Polymers)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 22144-77-0 (Cytochalasin D)
RN  - 67526-95-8 (Thapsigargin)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - SRQ9WWM084 (latrunculin A)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - Am J Physiol Cell Physiol. 2001 Jun;280(6):C1634-5. PMID: 11350759
MH  - Actins/metabolism
MH  - Atrial Natriuretic Factor/analysis/pharmacology
MH  - Bridged Bicyclo Compounds, Heterocyclic/pharmacology
MH  - Calcium/*metabolism
MH  - Carcinogens/pharmacology
MH  - *Carcinoma, Hepatocellular
MH  - Cell Compartmentation/drug effects/physiology
MH  - Cytochalasin D/pharmacology
MH  - Cytoskeleton/drug effects/metabolism
MH  - Humans
MH  - *Liver Neoplasms
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Polymers/metabolism
MH  - Thapsigargin/pharmacology
MH  - Thiazoles/pharmacology
MH  - Thiazolidines
MH  - Tumor Cells, Cultured/chemistry/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - ras Proteins/analysis
EDAT- 2001/05/15 10:00
MHDA- 2001/06/23 10:01
CRDT- 2001/05/15 10:00
PHST- 2001/05/15 10:00 [pubmed]
PHST- 2001/06/23 10:01 [medline]
PHST- 2001/05/15 10:00 [entrez]
AID - 10.1152/ajpcell.2001.280.6.C1636 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2001 Jun;280(6):C1636-44. doi: 
      10.1152/ajpcell.2001.280.6.C1636.