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Differential regulation of AMP-activated kinase and AKT kinase in response to oxygen availability in crucian carp (Carassius carassius)

机译:oxygen鱼对氧气供应的响应,AMP激活激酶和AKT激酶的差异调节

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Differential regulation of AMP-activated kinase and AKT kinase in response to oxygen availability in crucian carp (Carassius carassius). Am J Physiol Regul Integr Comp Physiol 295: R1803-R1814, 2008. First published October 15, 2008; doi:10.1152/ajpregu.90590.2008.俥 investigated whether two ki-nases critical for survival during periods of energy deficiency in anoxia-intolerant mammalian species, AMP-activated kinase (AMPK), and protein kinase B (AKT), are equally important for hypoxic/anoxic survival in the extremely anoxia-tolerant crucian carp (Carassius carassius). We report that phosphorylation of AMPK and AKT in heart and brain showed small changes after 10 days of severe hypoxia (0.3 mg O2/I at 9H). In contrast, anoxia exposure (0.01 mg O2/l at 8H) substantially increased AMPK phosphorylation but decreased AKT phosphorylation in carp heart and brain, indicating activation of AMPK and deactivation of AKT. In agreement, blocking the activity of AMPK in anoxic fish in vivo with 20 mg/kg Compound C resulted in an elevated metabolic rate (as indicated by increased ethanol production) and tended to reduce energy charge. This is the first in vivo experiment with Compound C in a nonmammalian vertebrate, and it appears that AMPK plays a role in mediating anoxic metabolic depression in crucian carp. Real-time RT-PCR analysis of the investigated AMPK subunit revealed that the most likely composition of subunits in the carp heart is a2, betab, 72a, whereas a more even expression of subunits was found in the brain. In the heart, expression of the regulatory 72-subunit increased in the heart during anoxia. In the brain, expression of the cu-, a2-, and 71-subunits decreased with anoxia exposure, but expression of the 72-subunit remained constant. Combined, our findings suggest that AMPK and AKT may play important, but opposing roles for hypoxic/anoxic survival in the anoxia-tolerant crucian carp
机译:oxygen鱼(Carassius carassius)响应氧气供应而对AMP激活激酶和AKT激酶的差异调节。 Am J Physiol Regul Integr Comp Physiol 295:R1803-R1814,2008年。2008年10月15日首次发布; doi:10.1152 / ajpregu.90590.2008。俥研究了两个缺氧条件是否对缺氧耐性哺乳动物物种能量缺乏期间的生存至关重要:AMP激活激酶(AMPK)和蛋白激酶B(AKT)对于极度耐缺氧的cru鱼(Carassius carassius)的低氧/缺氧存活率。我们报告说,严重缺氧10天后(9H时为0.3 mg O2 / I),心脏和大脑中AMPK和AKT的磷酸化表现出很小的变化。相反,缺氧暴露(在8H时为0.01 mg O2 / l)显着增加了鲤鱼心和脑中AMPK的磷酸化,但降低了AKT的磷酸化,表明AMPK活化和AKT失活。一致的是,用20 mg / kg的化合物C阻断体内缺氧鱼类中AMPK的活性会导致新陈代谢率提高(如乙醇产量增加所指示),并倾向于减少能量消耗。这是在非哺乳动物脊椎动物中用化合物C进行的第一个体内实验,看来AMPK在media鱼的缺氧代谢抑制中起着作用。对所研究的AMPK亚基的实时RT-PCR分析显示,鲤鱼心脏中最可能的亚基组成是a2,betab,72a,而在大脑中发现的亚基表达更为均匀。在心脏中,缺氧期间心脏中调节性72-亚基的表达增加。在大脑中,cu-,a2-和71亚基的表达随缺氧而降低,但72亚基的表达保持恒定。综合来看,我们的研究结果表明,AMPK和AKT可能在耐缺氧cru鱼的低氧/缺氧生存中发挥重要作用,但存在相反的作用

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