Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity.
Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity.
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DOI：
10.1038/s41598-017-13096-7
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发表时间：
2017-10-06
影响因子：
4.6
通讯作者：
Zuurbier CJ
中科院分区：
文献类型：
--
作者：
Nederlof R;van den Elshout MAM;Koeman A;Uthman L;Koning I;Eerbeek O;Weber NC;Hollmann MW;Zuurbier CJ
亲环素D（CypD）的缺乏和线粒体结合己糖激酶II（mtHKII）的存在都保护心脏免受缺血/再灌注（I/R）损伤。目前尚不清楚CypD是否决定心脏中mtHKII的量。我们研究CypD是否影响mtHK在常氧，缺血和预处理的离体小鼠心脏。野生型（WT）和CypD−/−小鼠心脏仅用葡萄糖灌注，并进行25分钟的缺血和再灌注。在基线时，心脏之间的细胞溶质和mtHK相似。CypD消融可保护I/R损伤并增加缺血预处理（IPC）效应，而不影响缺血终末mtHK。当心脏灌注葡萄糖、谷氨酰胺、丙酮酸和乳酸时，制备物更稳定，CypD消融导致更多的保护，这与mtHK活性增加有关，IPC几乎没有额外保护的空间。总之，在仅葡萄糖灌注的心脏中，CypD的缺失与终末缺血性心肌-HK结合无关。相比之下，在生理上更相关的多底物灌注模型中，CypD的缺失与mtHK活性增加相关，这可能解释了对I/R损伤的保护增加。
Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic and preconditioned isolated mouse hearts. Wild type (WT) and CypD−/− mouse hearts were perfused with glucose only and subjected to 25 min ischemia and reperfusion. At baseline, cytosolic and mtHK was similar between hearts. CypD ablation protected against I/R injury and increased ischemic preconditioning (IPC) effects, without affecting end-ischemic mtHK. When hearts were perfused with glucose, glutamine, pyruvate and lactate, the preparation was more stable and CypD ablation−resulted in more protection that was associated with increased mtHK activity, leaving little room for additional protection by IPC. In conclusion, in glucose only-perfused hearts, deletion of CypD is not associated with end-ischemic mitochondrial-HK binding. In contrast, in the physiologically more relevant multiple-substrate perfusion model, deletion of CypD is associated with an increased mtHK activity, possibly explaining the increased protection against I/R injury.
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DOI：
10.1085/jgp.201310968
发表时间：
2013-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Calmettes G;John SA;Weiss JN;Ribalet B
通讯作者：
Ribalet B
影响因子：
10.8
作者：
Hausenloy DJ;Lim SY;Ong SG;Davidson SM;Yellon DM
通讯作者：
Yellon DM
影响因子：
5
作者：
Nadtochiy SM;Urciuoli W;Zhang J;Schafer X;Munger J;Brookes PS
通讯作者：
Brookes PS
影响因子：
3.3
作者：
Guerel, Ebru;Smeele, Kirsten M.;Zuurbier, Coert J.
通讯作者：
Zuurbier, Coert J.
DOI：
10.1152/ajpheart.01117.2002
发表时间：
2003-07-01
影响因子：
4.8
作者：
Lloyd, S;Brocks, C;Chatham, JC
通讯作者：
Chatham, JC