AMPK is involved in mediation of erythropoietin influence on metabolic activity and reactive oxygen species production in white adipocytes.
AMPK is involved in mediation of erythropoietin influence on metabolic activity and reactive oxygen species production in white adipocytes.
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DOI：
10.1016/j.biocel.2014.06.008
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Wu, Wenling
中科院分区：
文献类型：
--
作者：
Wang, Yanfeng;Wu, Wenling
关键词：
促红细胞生成素被发现在红细胞生成过程中起着不可或缺的作用，已被用于治疗促红细胞生成素缺乏患者的某些红细胞疾病。由于红细胞生成素受体的表达，促红细胞生成素的生物活性被发现延伸到非红系组织。我们先前证明，促红细胞生成素通过过氧化体增殖物激活受体α和Sirtuin1促进代谢活性和白色脂肪细胞的褐变，从而增加线粒体的功能和能量消耗。在此，我们报道了促红细胞生成素可能通过钙/钙调蛋白依赖的蛋白激酶激活AMP激活的蛋白激酶，在饮食诱导的肥胖小鼠的白色脂肪组织中也是如此。促红细胞生成素通过增加AMP激活的蛋白激酶活性来增加细胞烟酰胺腺嘌呤二核苷酸，可能导致Sirtuin1的激活。AMP激活的蛋白激酶抑制了促红细胞生成素介导的细胞氧化功能的增加，包括增加氧耗率、脂肪酸利用和诱导关键代谢基因。在低氧条件下，脂肪细胞产生更多的活性氧物种，促红细胞生成素减少了活性氧物种，增加了抗氧化基因的表达，提示促红细胞生成素可能对脂肪细胞的氧化应激起到保护作用。促红细胞生成素还通过增加AMP激活的蛋白激酶来逆转缺氧引起的烟酰胺腺嘌呤二核苷酸的增加。此外，AMP激活的蛋白激酶被发现与促红细胞生成素刺激的氧耗率增加、脂肪酸氧化和线粒体基因表达有关。AMP激活的蛋白激酶下调受损的促红细胞生成素刺激的抗氧化基因表达增加。总而言之，我们的发现确定了AMP激活的蛋白激酶参与了促红细胞生成素信号调节脂肪细胞的氧化还原状态和代谢活动。
Erythropoietin, discovered for its indispensable role during erythropoiesis, has been used in the therapy for selected red blood cell disorders in erythropoietin-deficient patients. The biological activities of erythropoietin have been found to extend to non-erythroid tissues due to the expression of erythropoietin receptor. We previously demonstrated that erythropoietin promotes metabolic activity and white adipocytes browning to increase mitochondrial function and energy expenditure via peroxisome proliferator-activated receptor alpha and Sirtuin1. Here we report that AMP-activated protein kinase was activated by erythropoietin possibly via Ca2+/calmodulin-dependent protein kinase kinase in adipocytes as well as in white adipose tissue from diet induced obese mice. Erythropoietin increased cellular Nicotinamide adenine dinucleotide via increased AMP-activated protein kinase activity, possibly leading to Sirtuin1 activation. AMP-activated protein kinase knock down reduced erythropoietin mediated increase in cellular oxidative function including the increased oxygen consumption rate, fatty acid utilization and induction of key metabolic genes. Under hypoxia, adipocytes were found to generate more reactive oxygen species, and erythropoietin reduced the reactive oxygen species and increased antioxidant gene expression, suggesting that erythropoietin may provide protection from oxidative stress in adipocytes. Erythropoietin also reversed increased nicotinamide adenine dinucleotide by hypoxia via increased AMP-activated protein kinase. Additionally, AMP-activated protein kinase is found to be involved in erythropoietin stimulated increase in oxygen consumption rate, fatty acid oxidation and mitochondrial gene expression. AMP-activated protein kinase knock down impaired erythropoietin stimulated increases in antioxidant gene expression. Collectively, our findings identify the AMP-activated protein kinase involvement in erythropoietin signaling in regulating adipocyte cellular redox status and metabolic activity.
影响因子：
1.6
作者：
Bogdanov, Andrey;Rijmen, Vincent
通讯作者：
Rijmen, Vincent