Pyruvate dehydrogenase activation precedes the down-regulation of fatty acid oxidation in monocrotaline-induced myocardial toxicity in mice
Pyruvate dehydrogenase activation precedes the down-regulation of fatty acid oxidation in monocrotaline-induced myocardial toxicity in mice
复制标题
在野百合碱诱导的小鼠心肌毒性中，丙酮酸脱氢酶激活先于脂肪酸氧化下调
DOI：
10.1007/s00380-018-1293-3
复制
发表时间：
2018
影响因子：
1.5
通讯作者：
Minamisawa Susumu
中科院分区：
文献类型：
--
作者：
Nakai Gaku;Shimura Daisuke;Uesugi Ken;Kajimura Ichige;Jiao Qibin;Kusakari Yoichiro;Soga Tomoyoshi;Goda Nobuhito;Minamisawa Susumu
受损心脏的脂肪酸（FA）氧化受损，糖酵解促进。然而，心肌代谢损害早期阶段的因素仍不清楚。以0.3 mg/g体重的剂量每周两次皮下给予C57 B6小鼠野百合碱（MCT），持续3或6周。在给药后3周和6周对右心室和左心室进行毛细管电泳-质谱代谢组学分析。我们还检测了关键代谢分子的mRNA和蛋白质水平。尽管通过超声心动图和组织学分析在MCT给药小鼠中未发现PH和右心室衰竭的证据，但即使在第3周，右心室和左心室中的应激标志物（如TNFα和IL-6）的表达水平也升高，表明存在心肌损伤。6周时，三羧酸（TCA）循环中的代谢产物减少，糖酵解中的代谢产物增加。6周时FA氧化相关因子的表达水平下降。丙酮酸脱氢酶（PDH）的磷酸化水平在3周时显著降低。FA氧化和TCA循环下调，而糖酵解部分上调MCT诱导的心肌损伤。PDH激活先于这些改变，表明PDH激活是补偿心肌损伤引起的轻微代谢损伤的最早事件之一。
Fatty acid (FA) oxidation is impaired and glycolysis is promoted in the damaged heart. However, the factor(s) in the early stages of myocardial metabolic impairment remain(s) unclear. C57B6 mice were subcutaneously administered monocrotaline (MCT) in doses of 0.3 mg/g body weight twice a week for 3 or 6 weeks. Right and left ventricles at 3 and 6 weeks after administration were subjected to capillary electrophoresis–mass spectrometry metabolomic analysis. We also examined mRNA and protein levels of key metabolic molecules. Although no evidence of PH and right ventricular failure was found in the MCT-administered mice by echocardiographic and histological analyzes, the expression levels of stress markers such as TNFα and IL-6 were increased in right and left ventricles even at 3 weeks, suggesting that there was myocardial damage. Metabolites in the tricarboxylic acid (TCA) cycle were decreased and those in glycolysis were increased at 6 weeks. The expression levels of FA oxidation-related factors were decreased at 6 weeks. The phosphorylation level of pyruvate dehydrogenase (PDH) was significantly decreased at 3 weeks. FA oxidation and the TCA cycle were down-regulated, whereas glycolysis was partially up-regulated by MCT-induced myocardial damage. PDH activation preceded these alterations, suggesting that PDH activation is one of the earliest events to compensate for a subtle metabolic impairment from myocardial damage.
登录
查看更多内容
吡咯里西啶生物碱野百合碱诱导大鼠肝 DNA 损伤的表征。
影响因子：
11.2
作者：
Petry,TW;Bowden,GT;Huxtable,RJ;Sipes,IG
通讯作者：
Sipes,IG
影响因子：
3.8
作者：
Copple, BL;Rondelli, CM;Roth, RA
通讯作者：
Roth, RA
影响因子：
3.5
作者：
Daicho, Takuya;Yagi, Tatsuya;Tanonaka, Kouichi
通讯作者：
Tanonaka, Kouichi
DOI：
10.1016/0378-8741(88)90098-0
发表时间：
1988-03
期刊：
Biomedical & environmental mass spectrometry
影响因子：
--
作者：
CK Winter;HJ Segall;AD Jones
通讯作者：
CK Winter;HJ Segall;AD Jones
影响因子：
2.5
作者：
Ezzat, Tarek;van den Broek, Maartje A. J.;Damink, Steven W. M. Olde
通讯作者：
Damink, Steven W. M. Olde