PMID- 10561609
OWN - NLM
STAT- MEDLINE
DCOM- 20021203
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 266
IP  - 2
DP  - 1999 Dec
TI  - Sphingomyelinase treatment of rat hepatocytes inhibits cell-swelling-stimulated
      glycogen synthesis by causing cell shrinkage.
PG  - 653-9
AB  - Breakdown of plasma-membrane sphingomyelin caused by TNF-alpha is known to
      inhibit glucose metabolism and insulin signalling in muscle and fat cells. In
      hepatocytes, conversion of glucose to glycogen is strongly activated by amino
      acid-induced cell swelling. In order to find out whether breakdown of
      plasma-membrane sphingomyelin also inhibits this insulin-independent process, the
      effect of addition of sphingomyelinase was studied in rat hepatocytes.
      Sphingomyelinase (but not ceramide) inhibited glycogen synthesis, caused cell
      shrinkage, decreased the activity of glycogen synthase a, but had no effect on
      phosphorylase a. Cell integrity was not affected by sphingomyelinase addition as 
      gluconeogenesis and the intracellular concentration of ATP were unchanged. As a
      control, glycogen synthesis was studied in HepG2 cells. In these cells, the basal
      rate of glycogen production was high, could not be stimulated by amino acids, nor
      be inhibited by sphingomyelinase. Regarding the mechanism responsible for the
      inhibition of glycogen synthase a, sphingomyelinase did not affect amino
      acid-induced, PtdIns 3-kinase-dependent, phosphorylation of p70S6 kinase, but
      caused an increase in intracellular chloride, which is known to inhibit glycogen 
      synthase phosphatase. It is concluded that the decrease in cell volume, following
      the breakdown of sphingomyelin in the plasma membrane of the hepatocyte, may
      contribute to the abnormal metabolism of glucose when TNF-alpha levels are high.
FAU - Van Sluijters, D A
AU  - Van Sluijters DA
AD  - Department of Biochemistry, Academic Medical Center, University of Amsterdam, The
      Netherlands.
FAU - Van Woerkom, G M
AU  - Van Woerkom GM
FAU - Aerts, J M
AU  - Aerts JM
FAU - Meijer, A J
AU  - Meijer AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Insulin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4R7X1O2820 (Chlorine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.4.1.- (Phosphorylases)
RN  - EC 2.4.1.11 (Glycogen Synthase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - Chlorine/metabolism
MH  - Glycogen/biosynthesis/*metabolism
MH  - Glycogen Synthase/metabolism
MH  - Hepatocytes/enzymology/*metabolism
MH  - Humans
MH  - Insulin/metabolism
MH  - Phosphorylases/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction
MH  - Sphingomyelin Phosphodiesterase/metabolism/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1999/11/24 09:00
MHDA- 2002/12/04 04:00
CRDT- 1999/11/24 09:00
PHST- 1999/11/24 09:00 [pubmed]
PHST- 2002/12/04 04:00 [medline]
PHST- 1999/11/24 09:00 [entrez]
AID - ejb914 [pii]
AID - 10.1046/j.1432-1327.1999.00914.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Dec;266(2):653-9. doi: 10.1046/j.1432-1327.1999.00914.x.