Estrogen regulates energy metabolic pathway and upstream adenosine 5'-monophosphate-activated protein kinase and phosphatase enzyme expression in dorsal vagal complex metabolosensory neurons during glucostasis and hypoglycemia.
Estrogen regulates energy metabolic pathway and upstream adenosine 5'-monophosphate-activated protein kinase and phosphatase enzyme expression in dorsal vagal complex metabolosensory neurons during glucostasis and hypoglycemia.
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DOI：
10.1002/jnr.23481
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发表时间：
2015-02
影响因子：
4.2
通讯作者：
Briski, Karen P.
中科院分区：
文献类型：
--
作者：
Tamrakar, Pratistha;Ibrahim, Baher A.;Gujar, Amit D.;Briski, Karen P.
关键词：
雌激素保护大脑免受生物能量损伤--低血糖--的能力尚不清楚。雌二醇可阻止后脑代谢感觉A2去甲肾上腺素能神经元中能量缺乏感受器--腺苷5‘-单磷酸活化蛋白激酶(AMPK)的低血糖激活。在这里，我们研究了雌激素通过控制燃料代谢和/或上游蛋白激酶/磷酸酶表达来调节A2 AMPK的假说。分别用胰岛素(INS)或赋形剂(V)注射雌二醇(E)或油(O)植入去卵巢雌性大鼠体内，激光显微切割法获取A2细胞。用免疫印迹法检测细胞裂解产物的糖酵解、三羧酸循环(TCA)、呼吸链和乙酰辅酶A-丙二酸辅酶A途径酶。E/V组与O/V组相比，A2磷酸果糖激酶(PFKL)、异柠檬酸脱氢酶、丙酮酸脱氢酶和ATP合成酶亚基表达增加；低血糖仅使E组PFKL和α-酮戊二酸脱氢酶表达增加。低血糖使两组O细胞内A2、Ca++/钙调蛋白依赖的蛋白激酶-β升高，而PP2A降低。A2磷酸AMPK水平在O/V与E/V相当，但仅在O低血糖时升高。这些结果表明，雌二醇在低血糖时代偿性上调底物分解代谢，并相应地维持A2代谢感觉神经元的能量稳定性，这一结果支持了激素作用的分子底物作为治疗靶点缓解低血糖脑损伤的潜在生存能力。
The ability of estrogen to shield the brain from the bio-energetic insult, hypoglycemia, is unclear. Estradiol prevents hypoglycemic activation of the energy deficit sensor, adenosine 5′-monophosphate-activated protein kinase (AMPK), in hindbrain metabolo-sensory A2 noradrenergic neurons. Here, we investigated the hypothesis that estrogen regulates A2 AMPK through control of fuel metabolism and/or upstream protein kinase/phosphatase enzyme expression. A2 cells were harvested by laser-microdissection after insulin (INS) or vehicle (V) injection of estradiol (E)- or oil (O)-implanted ovariectomized female rats. Cell lysates were evaluated by immunoblot for glycolytic, tricarboxylic acid cycle (TCA), respiratory chain, and acetyl CoA-malonyl CoA pathway enzymes. A2 phosphofructokinase (PFKL), isocitrate dehydrogenase, and pyruvate dehydrogenase and ATP synthase subunit profiles were elevated in E/V versus O/V; hypoglycemia augmented PFKL and alpha-ketoglutarate dehydrogenase expression in E only. Hypoglycemia increased A2 Ca++/calmodulin-dependent protein kinase-beta in O, while reducing PP2A in both groups. A2 phosphoAMPK levels were equivalent in O/V versus E/V, but elevated during hypoglycemia in O only. These results implicate estradiol in compensatory up-regulation of substrate catabolism and corresponding maintenance of energy stability of A2 metabolo-sensory neurons during hypoglycemia, outcomes that support the potential viability of molecular substrates for hormone action as targets for therapies alleviating hypoglycemic brain injury.
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影响因子：
4.1
作者：
Briski, KP;Marshall, ES;Sylvester, PW
通讯作者：
Sylvester, PW
影响因子：
3.2
作者：
Krebs, B;Kohlmannsperger, V;Kretzschmar, HA
通讯作者：
Kretzschmar, HA
影响因子：
5.3
作者：
Nilsen, Jon;Irwin, Ronald W.;Brinton, Roberta Diaz
通讯作者：
Brinton, Roberta Diaz
DOI：
10.1152/ajpregu.00177.2004
发表时间：
2005-12-01
影响因子：
2.8
作者：
Patil, GD;Briski, KP
通讯作者：
Briski, KP
影响因子：
3.3
作者：
Briski, K. P.;Cherian, A. K.;Vavaiya, K. V.
通讯作者：
Vavaiya, K. V.