PMID- 10424278
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20190817
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 31
IP  - 1
DP  - 1999 Jul
TI  - A possible role of nuclear ceramide and sphingosine in hepatocyte apoptosis in 
      rat liver.
PG  - 8-17
AB  - BACKGROUND/AIMS: Portal vein branch ligation induces apoptosis of hepatocytes in 
      the ligated lobes in rat liver. Sphingomyelin degradation was studied during the 
      process to evaluate its possible involvement in apoptosis in vivo. METHODS: DNA 
      scissions were detected by the terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL) and an agarose gel electrophoresis of DNA. Using 
      both ligated and non-ligated lobes, we measured activities of sphingomyelin 
      degradation enzymes and contents of their products in purified nuclei and plasma 
      membrane. RESULTS: DNA fragmentation was detectable in the ligated lobes at 90 
      min after the portal vein branch ligation by gel electrophoresis. At 15 h after 
      the ligation, 27% of hepatocytes became TUNEL-positive. Prior to the onset of 
      apoptosis, the activity of neutral sphingomyelinase increased in the nuclei of 
      hepatocytes in ligated lobes (30 min after the ligation). The increase in 
      sphingomyelinase paralleled its reaction product, ceramide. This was followed by 
      the elevation of ceramidase activity in nuclei (60 min after the ligation) in 
      association with an increase of its reaction product, sphingosine. Activities of 
      these two enzymes and their products increased for at least 90 min. These changes 
      were not observed in nuclei of the non-ligated lobes, or in the plasma membranes 
      from either ligated or non-ligated lobes. CONCLUSIONS: These results, specific to 
      the liver where apoptosis is being generated, suggest that nuclear sphingomyelin 
      breakdown with an accumulation of ceramide and/or sphingosine in nuclei may 
      induce the apoptosis of hepatocytes in vivo.
FAU - Tsugane, K
AU  - Tsugane K
AD  - First Department of Surgery, Research Institute for Disease Mechanism and 
      Control, Nagoya University School of Medicine, Japan.
FAU - Tamiya-Koizumi, K
AU  - Tamiya-Koizumi K
FAU - Nagino, M
AU  - Nagino M
FAU - Nimura, Y
AU  - Nimura Y
FAU - Yoshida, S
AU  - Yoshida S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Ceramides)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.23 (Ceramidases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
CIN - J Hepatol. 1999 Jul;31(1):161-4. PMID: 10424298
MH  - Amidohydrolases/*metabolism
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Membrane/enzymology
MH  - Cell Nucleus/*enzymology
MH  - Ceramidases
MH  - Ceramides/*physiology
MH  - DNA Fragmentation
MH  - In Situ Nick-End Labeling
MH  - Kinetics
MH  - Liver/*cytology/*physiology
MH  - Male
MH  - Portal Vein/*physiology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Sphingomyelin Phosphodiesterase/*metabolism
MH  - Sphingosine/*physiology
MH  - Time Factors
EDAT- 1999/07/29 00:00
MHDA- 1999/07/29 00:01
CRDT- 1999/07/29 00:00
PHST- 1999/07/29 00:00 [pubmed]
PHST- 1999/07/29 00:01 [medline]
PHST- 1999/07/29 00:00 [entrez]
AID - S0168-8278(99)80158-5 [pii]
AID - 10.1016/s0168-8278(99)80158-5 [doi]
PST - ppublish
SO  - J Hepatol. 1999 Jul;31(1):8-17. doi: 10.1016/s0168-8278(99)80158-5.