Protection of rat cardiac myocytes by fructose-1,6-bisphosphate and 2,3-butanedione.
Protection of rat cardiac myocytes by fructose-1,6-bisphosphate and 2,3-butanedione.
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DOI：
10.1371/journal.pone.0035023
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chien S
中科院分区：
文献类型：
--
作者：
Wheeler TJ;Chien S
本课组前期研究表明，果糖-1,6-二磷酸（FBP）增强了大鼠心肌细胞的低温保存和动物心脏低温保存后的功能恢复。然而，所涉及的机制尚不清楚。我们通过测试FBP效应是否由于细胞外钙的螯合导致细胞内钙水平降低而扩展了心肌细胞的研究。我们还测试了2,3-丁二酮单肟（BDM）、丙酮酸和腺嘌呤核苷酸前体的作用。心肌细胞在3°C缺血悬液中孵育，并在48至72小时内检查等量细胞的杆状形态保留情况，这是一种衡量活力的指标。在一些实验中测量了细胞质Ca2+水平。即使在孵育1或2天后加入5 mM的FBP也能降低死亡率。在新分离的细胞中，它导致细胞内钙水平比对照组低33%，在孵育一天后降低70%。EGTA对细胞死亡的保护作用与FBP相似。这些结果表明，FBP发挥保护作用的机制之一是通过螯合细胞外钙。BDM具有很强的保护作用，孵育1天后使胞质钙含量降低30%。与FBP一样，在孵育1或2天后添加BDM有效。BDM可能与FBP联合用于保护心脏组织。丙酮酸、腺嘌呤和核糖在低温期间提供很少或没有保护。
Earlier studies by our group showed that fructose-1,6-bisphosphate (FBP) enhances the hypothermic preservation of rat cardiac myocytes and the functional recovery of animal hearts after hypothermic storage. However, the mechanisms involved were not clear. We extended the cardiomyocyte studies by testing whether the FBP effects were due to chelation of extracellular calcium, leading to lower intracellular levels. We also tested effects of 2,3-butanedione monoxime (BDM), pyruvate, and adenine nucleotide precursors. Cardiomyocytes were incubated in ischemic suspension at 3°C, and aliquots examined over 48 to 72 hours for retention of rod-shaped morphology, a measure of viability. Cytosolic Ca2+ levels were measured in some experiments. FBP at 5 mM reduced the death rate even when added after one or two days of incubation. It caused cytosolic calcium levels that were 33% lower than controls in freshly-isolated cells and 70% lower after one day of incubation. EGTA protected against cell death similarly to FBP. These results indicated that one of the mechanisms by which FBP exerts protective effects is through chelation of extracellular calcium. BDM was strongly protective and reduced cytosolic calcium by 30% after one day of incubation. As with FBP, BDM was effective when added after one or two days of incubation. BDM may be useful in combination with FBP in preserving heart tissue. Pyruvate, adenine, and ribose provided little or no protection during hypothermia.
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DOI：
10.1152/ajpheart.1994.267.6.h2325
发表时间：
1994-12-01
影响因子：
4.8
作者：
HARDIN, CD;ROBERTS, TM
通讯作者：
ROBERTS, TM
影响因子：
5
作者：
Calafell, Roser;Boada, Jordi;Bermudez, Jordi
通讯作者：
Bermudez, Jordi
影响因子：
8.9
作者：
Chien, S;Zhang, FT;Gray, LA
通讯作者：
Gray, LA
影响因子：
6.1
作者：
Colston, VL;Wheeler, TJ
通讯作者：
Wheeler, TJ
影响因子：
4.3
作者：
Ehringer, WD;Chiang, B;Chien, S
通讯作者：
Chien, S