AMP-Activated Protein (AMPK) in Pathophysiology of Pregnancy Complications.
AMP-Activated Protein (AMPK) in Pathophysiology of Pregnancy Complications.
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DOI：
10.3390/ijms19103076
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发表时间：
2018-10-09
影响因子：
5.6
通讯作者：
Kanasaki K
中科院分区：
文献类型：
--
作者：
Kumagai A;Itakura A;Koya D;Kanasaki K
尽管全球孕产妇死亡率一直在下降，但2015年全球仍有30.3万例孕产妇死亡，其中99%发生在发展中国家。了解妊娠并发症的病理生理，有助于正确的产前保健，降低产前、围产期和新生儿的死亡率和患病率。在这篇综述中，我们集中在AMP激活的蛋白激酶（AMPK）作为妊娠并发症的调节器。AMPK是真核生物中保守的丝氨酸/苏氨酸激酶。在应激条件下，它调节细胞和全身的能量平衡。AMPK的功能是多种多样的，并且已知AMPK的失调与许多疾病如心血管疾病、糖尿病、炎性疾病和癌症相关。在妊娠期间，AMPK对于适当的胎盘分化、营养运输、母体和胎儿能量稳态以及保护胎膜是必需的。AMPK的激活剂如5-氨基咪唑-4-甲酰胺核糖核苷酸（AICAR）、白藜芦醇和二甲双胍在临床前恢复妊娠并发症如妊娠糖尿病（GDM）、先兆子痫、宫内生长受限和早产。我们还讨论了儿茶酚-O-甲基转移酶（COMT），一种代谢儿茶酚的酶，与AMPK在怀孕期间的关系。已知二甲双胍不能激活COMT缺陷小鼠中的AMPK，并且COMT的代谢物2-甲氧基乙醇（2-ME）恢复AMPK活性，表明COMT是AMPK的调节剂。这些报告表明AMPK激活剂可用于治疗各种妊娠并发症，然而，由于AMPK激活可能导致胎儿畸形，因此需要仔细分析才能安全使用AMPK激活剂。
Although the global maternal mortality ratio has been consistently reduced over time, in 2015, there were still 303,000 maternal deaths throughout the world, of which 99% occurred in developing countries. Understanding pathophysiology of pregnancy complications contributes to the proper prenatal care for the reduction of prenatal, perinatal and neonatal mortality and morbidity ratio. In this review, we focus on AMP-activated protein kinase (AMPK) as a regulator of pregnancy complications. AMPK is a serine/threonine kinase that is conserved within eukaryotes. It regulates the cellular and whole-body energy homeostasis under stress condition. The functions of AMPK are diverse, and the dysregulation of AMPK is known to correlate with many disorders such as cardiovascular disease, diabetes, inflammatory disease, and cancer. During pregnancy, AMPK is necessary for the proper placental differentiation, nutrient transportation, maternal and fetal energy homeostasis, and protection of the fetal membrane. Activators of AMPK such as 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), resveratrol, and metformin restores pregnancy complications such as gestational diabetes mellitus (GDM), preeclampsia, intrauterine growth restriction, and preterm birth preclinically. We also discuss on the relationship between catechol-O-methyltransferase (COMT), an enzyme that metabolizes catechol, and AMPK during pregnancy. It is known that metformin cannot activate AMPK in COMT deficient mice, and that 2-methoxyestradiol (2-ME), a metabolite of COMT, recovers the AMPK activity, suggesting that COMT is a regulator of AMPK. These reports suggest the therapeutic use of AMPK activators for various pregnancy complications, however, careful analysis is required for the safe use of AMPK activators since AMPK activation could cause fetal malformation.
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DOI：
10.1042/bj20091372
发表时间：
2010-01-27
期刊：
The Biochemical journal
影响因子：
--
作者：
Fogarty S;Hawley SA;Green KA;Saner N;Mustard KJ;Hardie DG
通讯作者：
Hardie DG
影响因子：
9.8
作者：
Egawa, Tatsuro;Hamada, Taku;Hayashi, Tatsuya
通讯作者：
Hayashi, Tatsuya
AMPK 激活可预防产前应激引起的认知障碍：线粒体含量和氧化应激的调节。
影响因子：
7.4
作者：
Cao, Ke;Zheng, Adi;Peng, Zhihui
通讯作者：
Peng, Zhihui
影响因子：
5.3
作者：
Hernández JS;Barreto-Torres G;Kuznetsov AV;Khuchua Z;Javadov S
通讯作者：
Javadov S
影响因子：
3.6
作者：
Ahmadimoghaddam, Davoud;Zemankova, Lenka;Staud, Frantisek
通讯作者：
Staud, Frantisek