Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes.
Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes.
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新生大鼠心肌细胞中低剂量酒精减弱脂肪酸诱导的细胞凋亡。
DOI：
10.1152/ajpheart.00247.2004
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Hickson-Bick,DianeLM
中科院分区：
文献类型：
--
作者：
Sparagna,GenevieveC;Jones,ChadE;Hickson-Bick,DianeLM
适量饮酒已被证明可以降低冠心病的发病率和死亡率。乙醇通过激活与生长和存活相关的蛋白激酶等机制发挥其保护作用。我们在分离的新生大鼠心肌细胞中的结果表明，反复短期，低剂量暴露于乙醇足以激活生长和/或存活途径，涉及PKC-ε，Akt和AMP激活的激酶。此外，我们能够使用饱和脂肪酸棕榈酸酯诱导这些心肌细胞的凋亡。多次低剂量乙醇暴露预处理减弱棕榈酸酯的凋亡反应。这种保护表现为半胱天冬酶-3样活性的降低、细胞色素的线粒体损失减少和线粒体脂质心磷脂的损失减少。我们以前报道过，与非凋亡脂肪酸油酸酯孵育的细胞相比，棕榈酸酯孵育的心肌细胞导致活性氧的产生减少。在本研究中，我们观察到的超氧化物的生产和脂肪酸氧化率在心肌细胞用乙醇预处理，然后暴露于脂肪酸的增加。棕榈酸酯处理的细胞中的超氧化物产生的水平返回到乙醇暴露后在油酸酯处理的细胞中观察到的水平。结合我们观察到的AMP激活激酶活性的增加，我们认为乙醇预处理可以刺激心肌细胞内的氧化代谢和电子传递。我们推测，棕榈酸代谢的刺激可能通过防止心磷脂合成的不饱和前体分子的积累来保护心肌细胞。维持心磷脂水平可能足以防止细胞色素的线粒体丢失和下游半胱天冬酶的激活。
Moderate alcohol consumption has been shown to reduce the morbidity and mortality from coronary heart disease. Ethanol elicits its protective effects via mechanisms that include activation of protein kinases linked to growth and survival. Our results in isolated neonatal rat cardiomyocytes demonstrate that repeated short-term, low-dose exposure to ethanol is sufficient to activate the growth and/or survival pathways that involve PKC-ε, Akt, and AMP-activated kinase. In addition, we are able to induce apoptosis in these cardiomyocytes using the saturated fatty acid palmitate. Pretreatment with multiple low-dose ethanol exposures attenuates the apoptotic response to palmitate. This protection is manifested by a reduction in caspase-3-like activity, decreased mitochondrial loss of cytochromec, and decreased loss of the mitochondrial lipid cardiolipin. We previously reported that incubation of cardiomyocytes with palmitate results in decreased production of reactive oxygen species compared with cells incubated with the nonapoptotic fatty acid oleate. In the present study, we observed an increase in the production of superoxide and the rates of fatty acid oxidation in cardiomyocytes pretreated with ethanol and then exposed to fatty acids. The level of superoxide production in palmitate-treated cells returns to the levels observed in oleate-treated cells after ethanol exposure. Taken together with our observed increase in AMP-activated kinase activity, we propose that ethanol pretreatments stimulate oxidative metabolism and electron transport within cardiomyocytes. We postulate that stimulation of palmitate metabolism may protect cardiomyocytes by preventing accumulation of unsaturated precursor molecules of cardiolipin synthesis. Maintaining cardiolipin levels may be sufficient to prevent the mitochondrial loss of cytochromecand the downstream activation of caspases.
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慢性乙醇诱导的心肌保护需要激活线粒体 K(ATP) 通道。
DOI：
10.1006/jmcc.2000.1233
发表时间：
2000
期刊：
Journal of molecular and cellular cardiology.
影响因子：
--
作者：
Zhu,P;Zhou,HZ;Gray,MO
通讯作者：
Gray,MO
影响因子：
15.9
作者：
GOTTLIEB, RA;BURLESON, KO;ENGLER, RL
通讯作者：
ENGLER, RL
影响因子：
10.8
作者：
Nishino, Y;Miura, T;Shimamoto, K
通讯作者：
Shimamoto, K
K(ATP) 通道介导慢性乙醇摄入的有益作用。
DOI：
10.1152/ajpheart.2000.279.5.h2574
发表时间：
2000
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Pagel,PS;Toller,WG;Gross,ER;Gare,M;Kersten,JR;Warltier,DC
通讯作者：
Warltier,DC
DOI：
10.1152/ajpheart.00275.2002
发表时间：
2002-09-01
影响因子：
4.8
作者：
Soltys, CLM;Buchholz, L;Dyck, JRB
通讯作者：
Dyck, JRB