Acute alcohol modulates cardiac function as PI3K/Akt regulates oxidative stress.
Acute alcohol modulates cardiac function as PI3K/Akt regulates oxidative stress.
复制标题
DOI：
10.1111/acer.12459
复制
发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Haddad GE
中科院分区：
文献类型：
--
作者：
Umoh NA;Walker RK;Al-Rubaiee M;Jeffress MA;Haddad GE
酒精滥用对心肌的临床表现包括随着心力衰竭的发展而出现收缩力缺陷。有趣的是，低酒精摄入量与降低心血管疾病的风险有关。尽管人们对酒精性心肌病和低剂量有益心血管的作用提出了几种假设，但其确切机制和介质在很大程度上仍未明确。我们假设PI3K/Akt对氧化应激的调节在急性酒精暴露的心功能结果中起关键作用。因此，在PI3K/Akt激活剂（IGF-1 0.1 μM或组成型活性PI3K: Ad）存在或不存在的情况下，对急性暴露于低（LA: 5 mM）、中等（MA: 25 mM）和高（HA: 100 mM）酒精的大鼠心脏组织和心肌细胞进行氧化应激标志物评估。BD110转染)或抑制剂(LY294002 1 μMor akt阴性构建体Ad。一种蛋白激酶(K179M)转染)。急性LA降低Akt、超氧化物歧化酶（SOD-3）和NFκB、ERK1、p38 MAPK基因的表达。急性HA仅使SOD-3和NFκB升高。这些作用通常被Ad抑制。Akt(K179M)， Ad增强。BD110转染。与此同时，LA降低了Akt的活性，而HA则增强了Akt的活性，这一作用被IGF-1逆转，并被Ad抑制。一种蛋白激酶(K179M),分别。此外，LA降低了caspase 3/7活性和氧化应激，而HA提高了这两种酶的活性。前者被阻断，而后者被Ad.Akt（K179M）增强。PI3K/Akt激活则相反。这转化为HA的活力降低，对LA没有影响。在功能水平上，急性LA主要通过增加搏量来改善心输出量和射血分数。这伴随着增强的收缩期末期压力-容积关系和预负荷可恢复的卒中功。HA则有相反的效果。LY可减轻LA和HA的体内功能作用，IGF-1可增强其体内功能作用。急性LA和HA似乎通过调节氧化应激而相反地影响心功能，其中PI3K/Akt起关键作用。
Clinical manifestations of alcohol abuse on the cardiac muscle include defective contractility with the development of heart failure. Interestingly, low alcohol consumption has been associated with reduced risk of cardiovascular disease. Although several hypotheses have been postulated for alcoholic cardiomyopathy and for the low-dose beneficial cardiovascular effects, the precise mechanisms and mediators remain largely undefined. We hypothesize that modulation of oxidative stress by PI3K/Akt plays a key role in the cardiac functional outcome to acute alcohol exposure. Thus, acutely exposed rat cardiac tissue and cardiocytes to low (LA: 5 mM), moderate (MA: 25 mM), and high (HA: 100 mM) alcohol were assessed for markers of oxidative stress in the presence and absence of PI3K/Akt activators (IGF-1 0.1 μM or constitutively active PI3K: Ad.BD110 transfection) or inhibitor (LY294002 1 μMor Akt-negative construct Ad.Akt(K179M) transfection). Acute LA reduced Akt, superoxide dismutase (SOD-3) and NFκB, ERK1, and p38 MAPK gene expression. Acute HA only increased that of SOD-3 and NFκB. These effects were generally inhibited by Ad.Akt(K179M) and enhanced with Ad.BD110 transfection. In parallel, LA reduced but HA enhanced Akt activity, which was reversed by IGF-1 and inhibited by Ad.Akt(K179M), respectively. Also, LA reduced caspase 3/7 activity and oxidative stress, while HA increased both. The former was blocked, while the latter effect was enhanced by Ad.Akt(K179M). The reverse was true with PI3K/Akt activation. This translated into reduced viability with HA, with no effect with LA. On the functional level, acute LA improved cardiac output and ejection fraction, mainly through increased stroke volume. This was accompanied with enhanced end-systolic pressure–volume relationship and preload recruitable stroke work. Opposite effect was recorded for HA. LA and HA in vivo functional effects were alleviated by LY and enhanced by IGF-1 treatment. Acute LA and HA seem to oppositely affect cardiac function through modulation of oxidative stress where PI3K/Akt plays a pivotal role.
登录
查看更多内容
影响因子：
3.7
作者：
Ham, Young-Mi;Mahoney, Sarah Jane
通讯作者：
Mahoney, Sarah Jane
DOI：
10.1111/j.1530-0277.2011.01522.x
发表时间：
2011-10-01
影响因子：
3.2
作者：
Childs, Emma;O'Connor, Sean;de Wit, Harriet
通讯作者：
de Wit, Harriet
DOI：
10.1111/j.1530-0277.2008.00628.x
发表时间：
2008-05-01
影响因子：
3.2
作者：
Haddad, Georges E.;Saunders, Lori;Gwathmey, Judith K.
通讯作者：
Gwathmey, Judith K.
DOI：
10.3109/14756366.2011.654114
发表时间：
2013-06-01
影响因子：
5.6
作者：
Akca, Hakan;Demiray, Aydin;Tokgun, Onur
通讯作者：
Tokgun, Onur
影响因子：
3.7
作者：
Leychenko A;Konorev E;Jijiwa M;Matter ML
通讯作者：
Matter ML