利用腺病毒轉殖增加環氧酵素一型及前列環素合成素的基因表現,對心臟缺血再灌流後心臟損傷之保護。
Date Issued
2005
Date
2005
Author(s)
陳錦澤
DOI
932314B002203
Abstract
1
Prsotacyclin (PGI2) has been shown
to prevent ischemic cardiac damage and
stable PGI2 analogs are shown to exert
cardioprotective actions by increasing
blood flow, reducing platelet aggregation
and direct cardiac protection In this study,
we delivered the adenovirus containing
COX-1/PGIS which is the key productive
enzyme of PGI2 , using a catheter-based
technique to investigate the signaling
mechanism mediated by PGI2 in
protection against cardiomyocyte
apoptosis induced by acute
ischemia/reperfusion. After
adenovirus-mediated gene delivery, highly
efficient and specific expression of green
fluorescent protein, or recombinant
human COX-1 and PGIS were identified
in the left ventricle. Delivery of the PGI2
gene 5 days before ischemia/reperfusion
attenuated myocardial apoptosis identified
by in situ dUTP nick-end labeling and
DNA laddering, and the effect was
blocked by the cAMP antagonist which
induced signal by PGI2 .
Adv-COX-1/PGIS gene transfer increased
phosphorylation of Akt but reduced and
caspase-3 activities in the heart. The
effects Adv-COX-1/PGIS gene transfer on
phosphorylation of Akt and caspase-3
activities were blocked by LY294002(PI3
kinase inhibitor and by CAY(cAMP
inhibitor).Furthermore, Adv-COX-1/PGIS
gene transfer in cultured cardiomyocytes,
also attenuated apoptosis induced by
hypoxia/reoxygenation, which was
accompanied by increased phospho-AKT
and eNOS but reduced caspase-9 and
caspase-3 activities. Phospho-AKT and
caspase-3 activities were both blocked by
Ad.DN-Akt andCAY and LY294002.
These results indicate that
Adv-COX-1/PGIS gene transfer protects
against cardiomyocyte apoptosis induced
by ischemia/reperfusion injury through the
PI3 kinase-Akt-eNOS -caspase signaling
pathway.
Prsotacyclin (PGI2) has been shown
to prevent ischemic cardiac damage and
stable PGI2 analogs are shown to exert
cardioprotective actions by increasing
blood flow, reducing platelet aggregation
and direct cardiac protection In this study,
we delivered the adenovirus containing
COX-1/PGIS which is the key productive
enzyme of PGI2 , using a catheter-based
technique to investigate the signaling
mechanism mediated by PGI2 in
protection against cardiomyocyte
apoptosis induced by acute
ischemia/reperfusion. After
adenovirus-mediated gene delivery, highly
efficient and specific expression of green
fluorescent protein, or recombinant
human COX-1 and PGIS were identified
in the left ventricle. Delivery of the PGI2
gene 5 days before ischemia/reperfusion
attenuated myocardial apoptosis identified
by in situ dUTP nick-end labeling and
DNA laddering, and the effect was
blocked by the cAMP antagonist which
induced signal by PGI2 .
Adv-COX-1/PGIS gene transfer increased
phosphorylation of Akt but reduced and
caspase-3 activities in the heart. The
effects Adv-COX-1/PGIS gene transfer on
phosphorylation of Akt and caspase-3
activities were blocked by LY294002(PI3
kinase inhibitor and by CAY(cAMP
inhibitor).Furthermore, Adv-COX-1/PGIS
gene transfer in cultured cardiomyocytes,
also attenuated apoptosis induced by
hypoxia/reoxygenation, which was
accompanied by increased phospho-AKT
and eNOS but reduced caspase-9 and
caspase-3 activities. Phospho-AKT and
caspase-3 activities were both blocked by
Ad.DN-Akt andCAY and LY294002.
These results indicate that
Adv-COX-1/PGIS gene transfer protects
against cardiomyocyte apoptosis induced
by ischemia/reperfusion injury through the
PI3 kinase-Akt-eNOS -caspase signaling
pathway.
Publisher
臺北市:國立臺灣大學醫學院內科
Type
report
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