PMID- 9716505
OWN - NLM
STAT- MEDLINE
DCOM- 19981022
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 334 ( Pt 2)
IP  - Pt 2
DP  - 1998 Sep 1
TI  - Cell-cycle-dependent changes in ceramide levels preceding retinoblastoma protein 
      dephosphorylation in G2/M.
PG  - 457-61
AB  - Ceramide functions as a growth-inhibitory lipid-signalling molecule and might 
      have a role in mediating the effects of extracellular agents on cell growth, 
      differentiation and senescence. Here we investigate the roles of ceramide in cell 
      cycle progression. With the use of the model of serum withdrawal, we were able to 
      synchronize Wi-38 human diploid fibroblasts at different stages of cell cycle. 
      Serum stimulation resulted in G0 to G1/S progression as determined by flow 
      cytometric analysis and [3H]thymidine incorporation. Analyses of endogenous 
      ceramide levels demonstrated that ceramide levels remained relatively constant on 
      serum stimulation, indicating that ceramide might not be critical during G1/S 
      transition. Treating exponentially growing Wi-38 human diploid fibroblasts with 
      nocodazole led to cell cycle arrest at the G2/M phase of the cell cycle; 2 h 
      after the removal of nocodazole, retinoblastoma (Rb) protein became 
      dephosphorylated and the cells exited from G2/M and moved to the G1 phase of the 
      new cycle. When cells were released from G2/M block by nocodazole, and before Rb 
      protein dephosphorylation, endogenous ceramide levels transiently increased up to 
      2-fold at 0.5 h after the removal of nocodazole. Fumonisin B1, an inhibitor of 
      ceramide synthase, inhibited the elevation of ceramide levels. Desipramine and 
      SR33557, both acid sphingomyelinase inhibitors, did not have an appreciable 
      effect on the elevation of ceramide levels. Furthermore, fumonisin B1 inhibited 
      Rb protein dephosphorylation induced by endogenous ceramide but not by exogenous 
      ceramide. These results demonstrate for the first time changes in ceramide during 
      cell cycle progression and suggest that ceramide synthesized de novo might 
      function as an endogenous modulator of Rb protein and cell cycle progression.
FAU - Lee, J Y
AU  - Lee JY
AD  - Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
FAU - Leonhardt, L G
AU  - Leonhardt LG
FAU - Obeid, L M
AU  - Obeid LM
LA  - eng
GR  - 1R29-AG-12467/AG/NIA NIH HHS/United States
GR  - 5T32 AG00029/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Carboxylic Acids)
RN  - 0 (Ceramides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fumonisins)
RN  - 0 (Indolizines)
RN  - 0 (Phenethylamines)
RN  - 0 (Retinoblastoma Protein)
RN  - 3ZZM97XZ32 (fumonisin B1)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.3.1.- (dihydroceramide desaturase)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - KU213XYO69 (fantofarone)
RN  - SH1WY3R615 (Nocodazole)
RN  - TG537D343B (Desipramine)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Carboxylic Acids/pharmacology
MH  - Cell Cycle/drug effects/*physiology
MH  - Cell Line
MH  - Ceramides/*metabolism
MH  - Desipramine/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts
MH  - *Fumonisins
MH  - G2 Phase
MH  - Humans
MH  - Indolizines/pharmacology
MH  - Kinetics
MH  - Mitosis
MH  - Nocodazole/pharmacology
MH  - Oxidoreductases/antagonists & inhibitors
MH  - Phenethylamines/pharmacology
MH  - Phosphorylation
MH  - Retinoblastoma Protein/*metabolism
MH  - Sphingomyelin Phosphodiesterase/antagonists & inhibitors
MH  - Thymidine/metabolism
PMC - PMC1219709
EDAT- 1998/08/26 00:00
MHDA- 1998/08/26 00:01
PMCR- 1999/03/01
CRDT- 1998/08/26 00:00
PHST- 1998/08/26 00:00 [pubmed]
PHST- 1998/08/26 00:01 [medline]
PHST- 1998/08/26 00:00 [entrez]
PHST- 1999/03/01 00:00 [pmc-release]
AID - 10.1042/bj3340457 [doi]
PST - ppublish
SO  - Biochem J. 1998 Sep 1;334 ( Pt 2)(Pt 2):457-61. doi: 10.1042/bj3340457.