X-Message-Number: 25733
Date: Sun, 27 Feb 2005 20:33:33 -0800 (PST)
From: Doug Skrecky <>
Subject: could menopause be delayed by sphingosine-1-phosphate?

FASEB J. 2005 Feb 23; [Epub ahead of print]
A central role for ceramide in the age-related acceleration of
apoptosis in the female germline.
  An age-dependent acceleration of apoptosis occurs in female germ
cells (oocytes), and this requires communication between the oocyte
and its surrounding somatic (cumulus) cells. Here we show in aged
mice that ceramide is translocated from cumulus cells into the
adjacent oocyte and induces germ cell apoptosis that can be prevented
by sphingosine-1-phosphate. Trafficking of ceramide requires gap
junction-dependent communication between the cumulus cells and the
oocyte as well as intact lipid rafts. Further, the occurrence of
the elevated incidence of apoptosis in oocytes of aged females is
concomitant with an enhanced sensitivity of the oocyte to a spike
in cytosolic ceramide levels, as well as increased bax mRNA and
Bax protein levels. Thus, the force driving the age-related increase
in female germ cell death is multifactorial, but changes in the
intercellular trafficking of ceramide, along with hypersensitivity
of oocytes to ceramide, are key factors in this process.

Shi Yan Sheng Wu Xue Bao. 2001 Dec;34(4):333-5
[Rapid induction of senescence-like changes in human umbilic vein
endothelial cells(HUVECs) by C6 ceramide]
  Ceramide, a key molecule in sphingolipid metabolism and a candidate
second messenger, has been shown to inhibit the activity of
phospholipase D. This biochemical pathway has been implicated to
regulate cell differentiation, apoptosis and cellular senescence.
Ceramide is generated in response to a number of extracellular
inducers(for example: TNF, IL-1 and Fas ligands etc.), and acts as
a second messenger to mediate many of the effects of these inducers.
HUVECs are the monolayer cells located inside the vein wall and play
an important role in the regulation of vein physiology and blood
function. It has been reported that the C6 ceramide can induce
senescence of WI-38 HDF and promote the activity of
beta-galactosidase, but, C2 ceramide has no such effect. In this
study, we investigated the role of C6 ceramide in the senescence
of HUVECs. 10 mumol/ml of C6 ceramide treatment for more than 72
can induce morphological alterations (such as: enlarged, flattened
and irregular cell body), cell cycle arrested at G1 phase and the
expression of the senescent histochemical marker-beta-galactosidase
in HUVECs. These results showed that C6 ceramide could induce
senescence-like changes of HUVECs. The detection of reactive oxygen
species(ROS) and the anti-oxidative ability of the cells showed that
the C6 ceramide induced senescence-like cells still have normal
ability of anti-oxidation. Further investigations are ongoing.

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