Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.6 (
RNA polymerase
)
34,946
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Generation of proapoptotic sphingolipids by neutral sphingomyelinase activation is an early response to hypoxia/reoxygenation (HR) in cardiomyocytes.
Factor associated with neutral sphingomyelinase activation
(
FAN
) mediates activation of sphingomyelinase and subsequent apoptosis. However, the participation of
FAN
in HR-induced cardiomyocyte cell death has not been elucidated. We therefore investigated the expression and role of
FAN
in rat cardiomyocytes. A cDNA was isolated from rat heart encoding putative rat
FAN
. Reverse
transcriptase
-polymerase chain reaction, immunoelectron microscopy, and immunofluorescence demonstrated for the first time the expression of
FAN
specifically in rat cardiomyocytes.
FAN
expression was confirmed by the finding that expression of a dominant-negative
FAN
almost completely abrogated HR-induced cell death, whereas overexpression of wild-type
FAN
led to an increase. Treatment of
FAN
and dominant-negative
FAN
--expressing cells with C2-ceramide produced substantial cell death, indicating dominant-negative
FAN
exerts its protective action by interfering with the activation of the sphingolipid cascade. Taking these results together, we conclude that
FAN
is a previously undescribed and important HR signaling component in the heart and that inhibition of
FAN
may provide a novel intervention point for reducing ischemia/reperfusion injury.
...
PMID:Factor associated with neutral sphingomyelinase activation and its role in cardiac cell death. 1263 70
