Epicatechin regulation of mitochondrial structure and function is opioid receptor dependent.

Epicatechin regulation of mitochondrial structure and function is opioid receptor dependent.
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DOI:
10.1002/mnfr.201300026
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发表时间:
2013-06
影响因子:
5.2
通讯作者:
Patel, Hemal H.
Patel, Hemal H.
中科院分区:
农林科学2区
文献类型:
--
作者:
Panneerselvam, Mathivadhani;Ali, Sameh S.;Finley, J. Cameron;Kellerhals, Sarah E.;Migita, Michael Y.;Head, Brian P.;Patel, Piyush M.;Roth, David M.;Patel, Hemal H.

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黄烷醇(-)-表儿茶素(Epi)是可可的一种成分,对人类的心脏有保护作用。我们前期的研究表明,Epi具有δ-阿片受体(DOR)结合活性,并具有心脏保护作用。在这里,我们研究了10天的Epi治疗对心脏线粒体呼吸,ROS产生,钙肿胀和线粒体膜流动性的影响。将小鼠随机分为四组:(1)对照组(生理盐水),(2)纳曲吲哚(Nalt; DOR拮抗剂),(3)Epi,和(4)Epi+Nalt,并通过口服管饲法接受1 mg kg-1 Epi或水。Nalt组每天ip 5 mg kg-1,持续10天。在状态3呼吸过程中,观察到Epi的线粒体呼吸和增强的自由基产生显着增加。此外,我们观察到线粒体膜的刚性和对Epi处理的钙诱导的线粒体肿胀的抗性显著增加。用Nalt阻断DOR导致Epi治疗的所有观察到的参数降低。这些发现表明,Epi诱导一种综合反应,包括心脏线粒体的代谢和结构变化,通过DOR产生更大的功能能力。表儿茶素的线粒体靶向作用可以解释在心脏保护上观察到的生理益处,并支持表儿茶素作为心脏保护模拟物的潜在临床应用。
The flavanol (-)-epicatechin (Epi), a component of cacao, has cardiac protective benefits in humans. Our previous study demonstrated Epi has δ-opioid receptor (DOR) binding activity and promotes cardiac protection. Here we examined the effects of 10 days of Epi treatment on: cardiac mitochondrial respiration, ROS production, calcium swelling, and mitochondrial membrane fluidity. Mice were randomized into four groups: (1) Control (Saline), (2) Naltrindole (Nalt; DOR antagonist), (3) Epi, and (4) Epi+Nalt and received 1 mg kg−1 Epi or water via oral gavage. Nalt groups received 5 mg kg−1 ip per day for 10 days. Significant increases in mitochondrial respiration and enhanced free radical production during state 3 respiration were observed with Epi. Additionally, we observed significant increases in rigidity of mitochondrial membranes and resistance to calcium induced mitochondrial swelling with Epi treatment. Blocking the DOR with Nalt resulted in decreases in all of the observed parameters by Epi treatment. These findings indicate that Epi induces an integrated response that includes metabolic and structural changes in cardiac mitochondria resulting in greater functional capacity via DOR. Mitochondrial targeted effects of epicatechin may explain the physiologic benefit observed on cardiac protection and support epicatechin’s potential clinical application as a cardiac protective mimetic.
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