DC Field | Value | Language |
dc.contributor.author | 陳錦澤 | zh_TW |
dc.creator | 陳錦澤 | zh_TW |
dc.date | 2002 | zh_TW |
dc.date.accessioned | 2006-07-26T03:20:51Z | - |
dc.date.accessioned | 2018-07-11T05:25:29Z | - |
dc.date.available | 2006-07-26T03:20:51Z | - |
dc.date.available | 2018-07-11T05:25:29Z | - |
dc.date.issued | 2002 | - |
dc.identifier | 902320B002144 | zh_TW |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/23574 | - |
dc.description.abstract | 大多數心血管方面的疾病,都會造成
心臟的肥大,初期的心臟肥大可以代償心
臟功能,然而持續性的心臟肥大,便會導
致心臟的衰竭。在心臟細胞,由於機械應
力或內生性生長因子的刺激作用下,會造
成心臟細胞的肥大,心臟細胞的過度肥大
有可能導致心臟機能受損,進一步引起心臟衰竭。內皮素(endothelin-1; ET-1)有
造成細胞肥大的作用,但對於此作用其細
胞內的機轉目前還不是很清楚,已知內皮
素可增加許多迅即基因如c-fos 、c-jun 及
egr-1 等的基因表現;另外,對一些與心
臟細胞的增大有關的基因如心房利鈉
(atrial natriuretic peptide)、肌凝蛋
白重鏈(myosin heavy chain)、骨骼肌肉
肌動蛋白(actin)等,也有增加它們基因表
現的作用。近來有許多研究報告指出活性
氧族群(r eactive oxygen species ;ROS )及一氧化氮(nitric oxide; NO)可於細胞內
扮演一訊號傳遞者的角色,所以在本研究
中,我們進一步觀察活性氧族群於內皮素
所誘發細胞肥大現象所扮演的角色,並進
而闡釋其可能的細胞內機轉。由本報告抗
氧化劑可抑制內皮素所誘發心臟細胞肥
大,可推測抗氧化劑,在臨床上相關心臟
肥大或心臟衰竭疾病的預防治療上具有運用潛力。 | zh_TW |
dc.description.abstract | OBJECTIVES: We dissected the molecular
regulatory mechanism of reactive oxygen
species (ROS) on endothelin-1-(
ET-1)-induced b-myosin heavy chain
(b-MyHC) gene expression and hypertrophic
signaling in neonatal rat cardiomyocytes.
BACKGROUND: ET-1 causes hypertrophy
in the cardiomyocytes. Expression of cardiac
b-MyHC gene is increased in response to
ET-1. Our previous study has demonstrated
that ET-1 increases intracellular reactive
oxygen species (ROS) in cardiomyocytes.
However, the intracellular regulatory
mechanism of ROS on ET-1-induced
b-MyHC gene expression and cardiac
hypertrophy still remains unclear.
METHODS: Cultured neonatal rat
cardiomyocytes were stimulated with ET-1,
3 H-leucine incorporation and the b-MyHC
gene promoter activities were examined. We
also examined the effects of antioxidant
pretreatment on ET-1-induced cardiac
hypertrophy and MAPK activties to elucidate
the redox-sensitive pathway in cardiomyocyte
hypertrophy and b-MyHC gene expression.
RESULTS: 3 H-Leucine incorporation and
b-MyHC promoter activities were increased
by ET-1. These ET-1 effects were blocked by
the specific ETA receptor antagonist BQ-485.
Cardiomyocytes treated with antioxidants
significantly reduced ET-1-induced
3 H-leucine incorporation and b-MyHC gene
promoter activities. ET-1 activated
mitogen-activated protein kinases (MAPKs;
extracellular signal-regulated kinase [ERK],
p38, and JNK), which were significantly
inhibited by antioxidants. Either PD98059 or SB203580 inhibited ET-1-increased 3 H-leucine incorporation, but only PD98059
decreased ET-1-induced b-MyHC promoter
activities. Co-transfection of dominant
negative mutant of Ras, Raf, and MEK1
decreased the ET-1-increased b-MyHC
promoter activities, suggesting that the
Ras-Raf-ERK pathway is required for ET-1
action. Deletion mapping revealed that the
deletion construct containing 273 base pairs
(bp) of b-MyHC 5’-flanking sequences
upstream from the transcription initiation site
is necessary and sufficient for ET-1-induced
increase of transcription, whereas the
construct containing only 188 bp of
5’-flanking region had no effect, indicating
the ET-1-responsive element(s) is located
between position -273 and –188 bp upstream
from the transcription start site. This minimal
construct of 273 bp upstream of transcription
initiation site in the b-MyHC promoter region
is also required for ROS-induced b-MyHC
expression.
CONCLUSIONS: These data demonstrate
that ROS involved in ET-1-induced
hypertrophic responses, b-MyHC expression
and mediated ET-1-induced activation of
MAPK pathways, which culminated in
hypertrophic responses and b-MyHC
expression. The ROS-MAPK
(ERK)-meditated pathway plays an essential
role in ET-1-induced hypertrophic responses
and b-MyHC expression in cardiomyocytes. | en |
dc.format | application/pdf | zh_TW |
dc.format.extent | 312143 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language | zh-TW | zh_TW |
dc.language.iso | zh_TW | - |
dc.publisher | 臺北市:國立臺灣大學醫學院內科 | zh_TW |
dc.rights | 國立臺灣大學醫學院內科 | zh_TW |
dc.subject | 內皮素 | zh_TW |
dc.subject | 活性氧族群 | zh_TW |
dc.subject | 乙型重鏈基因 | zh_TW |
dc.subject | 心臟細胞 | zh_TW |
dc.subject | 細胞肥大 | zh_TW |
dc.subject | endothelin-1 | en |
dc.subject | reactive oxygen
species | en |
dc.subject | beta-myosin heavy chain gene | en |
dc.subject | cardiomyocyte | en |
dc.subject | hypertrophy | en |
dc.title | 活性氧族群及一氧化氮於心臟細胞中調控內皮素所誘發乙型肌凝重鍊蛋白基因所扮演的角色 | zh_TW |
dc.title.alternative | Role of r eactive oxygen species and nitr ic oxide in modulation of
endothelin-1-induced beta-myosin heavy chain gene expr ession in
cardiomyocytes. | en |
dc.type | report | en |
dc.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/23574/1/902320B002144.pdf | - |
dc.coverage | 計畫年度:90;起迄日期:2001-08-01/2002-07-31 | zh_TW |
item.languageiso639-1 | zh_TW | - |
item.cerifentitytype | Publications | - |
item.fulltext | with fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_93fc | - |
item.openairetype | report | - |
item.grantfulltext | open | - |
Appears in Collections: | 醫學系
|