心肌細胞肥大導致心肌猝死的過程中,粒線體細胞色素氧化酵素的基因表現與蛋白活性變化

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 研究計劃 > Item 310902500/3091

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/3091

Title:	心肌細胞肥大導致心肌猝死的過程中,粒線體細胞色素氧化酵素的基因表現與蛋白活性變化 The Relationship of Mitochondrial Cytochrome-C-Oxidase Gene Expressions and Protein Activities in the Development of Cardiomyocytes Hypertrophy and Apotosis;Roles of IGF-I&II.
Authors:	黃志揚 Huang, Chih-Yang
Contributors:	中山醫學院生物化學研究所
Keywords:	細胞色素c氧化酵素;基因表現;心臟肥大 Cytochrome C oxidase;Gene expression;Cardiac hypertrophy
Date:	2001
Issue Date:	2010-12-07T09:23:46Z (UTC)
Abstract:	病理性心肌肥厚是引起心肌狹死的主要危險因子，但引發的分子轉並不清楚。在心肌細胞肥大過程中，粒腺體是主要能量供應來源。就目前所知，在心肌肥厚末期常因無充份的氧化能力，而導致心肌衰竭。另外證據顯示，細胞死亡蛋白（Bax）會由細胞質轉移至粒腺體表層，引發細胞色素－C一氧化酵素（COX）的流失而釋放至細胞質，進而活化染色體切割酵素（Caspases），切割DNA並導致心肌細胞死亡。我們曾採用新的大白鼠腹動脈完全結紮方式，來誘發心肌肥厚快速形成。手術後第二天，即可見心肌肥大及細胞色素－C一氧化酵素活性增加。但細胞色素－C一氧化酵素活性卻也在手術後第七天，隨著心肌纖維化的逐漸形成而漸漸減低。因此我們更進一步來檢測COX Vb的基因表現及COX protein量的變化，以了解COX基因表現及COX蛋白活性是否與COX蛋白量有絕對性的關係。藉此了解在心肌肥大轉惡為心肌纖維化及衰竭過程中，COX基因表現的角色。以Dot－blotting及in situ hybridization的技術來探討COX Vb的基因表現差異，發現基因表現變化與COX蛋白活性及心肌細胞肥大及衰竭有直接的關連性。未來並希望以先天性高血壓鼠（SHR）及重風性高血壓鼠（SHRSP）與此腹動脈完全結紮動物模型（Coarctation）作對照。 Chronic pressure overload leads to cardiac hypertrophy, the mechanism of which are not understood. The contribution of the mitochondrial compartment, the main energy source for cardiac hypertrophic growth, is especially little known. Here cardiac hypertrophy resulting from chronic of the rat abdominal aorta between the origins of the renal arteries. The study focused on the early (1 to 7 days) postsurgery peripd. Mean carotid systolic blood pressure remained at about 138mmHg the 7 day, in the shams but increased rapidly in coarcted rats (CR) to 175mmHg by day 3 and to 207 by day 7. CR heart weights increased over shams by 16% by day 3 (P<.001) and remained increased to day 7. Heart weight: body weight ratios were 3.39 and 4.49 (P<.001) at day 3 for sham and CR animals, respectively, and 3.32 and 4.81 (P<.001) at day 7. The CR heart weight increase was paralleled by an increase in cytochrome c oxidase (CYTOX) activity in isolated heart mitochondria. CR CYTOX activity was increased 44, 43 and 31% (P<.005, .001 and .005, respectively) over the shams at days 3, 5 and 7, respectively. Further, by day 3, the steady-state level of CYTOX subunit Vb mRNA, measured by dot blotting and IN SITU hybridation, in the CR hearts was the higher by 62% and 51% (P<.005), individually, than in the same day shams. Results suggest that the rapid cardiac hypertrophy observed here is mediated by an increase in mitochondrial energy-producing activity associated with a positive change in CYTOX gene expession. Supported by this grant.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3091
Appears in Collections:	[生化微生物免疫研究所] 研究計劃

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