Conditional knockout of myocyte focal adhesion kinase abrogates ischemic preconditioning in adult murine hearts.
Conditional knockout of myocyte focal adhesion kinase abrogates ischemic preconditioning in adult murine hearts.
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肌细胞粘着斑激酶的条件性敲除可消除成年小鼠心脏的缺血预处理。
DOI：
10.1161/jaha.113.000457
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发表时间：
2013
影响因子：
5.4
通讯作者：
VanderHeide,RichardS
中科院分区：
文献类型：
--
作者：
Perricone,AdamJ;Bivona,BenjaminJ;Jackson,FannieR;VanderHeide,RichardS
背景我们的实验室以前已经证明了基于细胞骨架的存活信号通路的重要性，使用体外模型缺血/再灌注（IR）。然而，这一途径在介导的压力引起的生存信号在vivo.Methods和ResultsThe重要的细胞骨架信号通路成员粘着斑激酶（FAK）的重要性是选择性删除在成人心肌细胞使用他莫昔芬诱导的Cre-Lox系统（α-MHC-MerCreMer）。采用聚合酶链反应（PCR）和蛋白质印迹法（Western blot）检测FAK基因敲除情况。对所有小鼠进行40分钟的冠状动脉闭塞，然后再灌注24小时。使用标准方案进行缺血预处理（IP）。对照组包括野生型（WT）和他莫昔芬处理的α-MHC-MerCreMer+/−/FAKWT/WT（实验对照）小鼠。肿瘤大小表示为风险区域的百分比。在WT小鼠中，与接受假手术实验方案的WT小鼠相比，IP显著增强了活化/磷酸化FAK的表达36.3%（P≤0.05; n=6个心脏[假手术]，n=4个心脏[IP]）。IP显著降低WT和实验对照小鼠的梗死面积（分别为43.7% vs 19.8%;P≤0.001; 44.7% vs 17.5%;P≤0.001）。在预处理的FAK KO和非预处理的对照组之间没有观察到梗死面积的差异（37.1%对43.7%对44.7%; FAK KO对WT对实验对照;P=NS）。IP引起WT小鼠中活化的磷脂酰肌醇-3-激酶（PI 3 K）p85/活化的Akt表达增加67.2%/88.8%，但未能增强预处理的FAK KO小鼠中两者的表达。结论我们的结果表明FAK是IP引起的心脏保护作用的重要介质，并为基于细胞骨架的信号传导是应激引起的生存信号传导的重要组成部分的假设提供了进一步的支持。
BackgroundOur laboratory has previously demonstrated the importance of a cytoskeletal‐based survival signaling pathway using in vitro models of ischemia/reperfusion (IR). However, the importance of this pathway in mediating stress‐elicited survival signaling in vivo is unknown.Methods and ResultsThe essential cytoskeletal signaling pathway member focal adhesion kinase (FAK) was selectively deleted in adult cardiac myocytes using a tamoxifen‐inducible Cre‐Lox system (α‐MHC‐MerCreMer). Polymerase chain reaction (PCR) and Western blot were performed to confirm FAK knockout (KO). All mice were subjected to a 40‐minute coronary occlusion followed by 24 hours of reperfusion. Ischemic preconditioning (IP) was performed using a standard protocol. Control groups included wild‐type (WT) and tamoxifen‐treated α‐MHC‐MerCreMer+/−/FAKWT/WT(experimental control) mice. Infarct size was expressed as a percentage of the risk region. In WT mice IP significantly enhanced the expression of activated/phosphorylated FAK by 36.3% compared to WT mice subjected to a sham experimental protocol (P≤0.05; n=6 hearts [sham], n=4 hearts [IP]). IP significantly reduced infarct size in both WT and experimental control mice (43.7% versus 19.8%;P≤0.001; 44.7% versus 17.5%;P≤0.001, respectively). No difference in infarct size was observed between preconditioned FAK KO and nonpreconditioned controls (37.1% versus 43.7% versus 44.7%; FAK KO versus WT versus experimental control;P=NS). IP elicited a 67.2%/88.8% increase in activated phosphatidylinositol‐3‐kinase (PI3K) p85/activated Akt expression in WT mice, but failed to enhance the expression of either in preconditioned FAK KO mice.ConclusionsOur results indicate that FAK is an essential mediator of IP‐elicited cardioprotection and provide further support for the hypothesis that cytoskeletal‐based signaling is an important component of stress‐elicited survival signaling.
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影响因子：
2.1
作者：
C. P. Read
通讯作者：
C. P. Read
Hymenolepis diminuta 线粒体中的转氢酶和厌氧磷酸化。
DOI：
--
发表时间：
1972
期刊：
Comparative biochemistry and physiology. B, Comparative biochemistry
影响因子：
--
作者：
H. J. Saz;J. Berta;J. Kowalski
通讯作者：
J. Kowalski
从锥虫血鞭毛虫 Crithidia fasciculata 中分离的线粒体中 H2O2 的产生和细胞色素 c 过氧化物酶活性。
影响因子：
3.9
作者：
J. Kusel;A. Boveris;B. T. Storey
通讯作者：
B. T. Storey
成年 Hymenolepis diminuta (Cestoda) 的线粒体 NADH 氧化酶活性。
DOI：
10.1016/0305-0491(82)90511-9
发表时间：
1982
期刊：
Comparative biochemistry and physiology. B, Comparative biochemistry
影响因子：
--
作者：
Fioravanti,CF
通讯作者：
Fioravanti,CF
Hymenolepis diminuta (Cestoda) 能量学中“苹果酸”酶与 NADPH:NAD 转氢酶的偶联。
DOI：
10.1016/0305-0491(84)90306-7
发表时间：
1984
期刊：
Comparative biochemistry and physiology. B, Comparative biochemistry
影响因子：
--
作者：
McKelvey,JR;Fioravanti,CF
通讯作者：
Fioravanti,CF