Different Expressions of HIF-1α and Metabolism in Brain and Major Visceral Organs of Acute Hypoxic Mice.
Different Expressions of HIF-1α and Metabolism in Brain and Major Visceral Organs of Acute Hypoxic Mice.
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急性缺氧小鼠脑及主要内脏器官中HIF-1α的不同表达及代谢
DOI：
10.3390/ijms22136705
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发表时间：
2021-06-23
影响因子：
5.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Xu L;Song H;Qiu Q;Jiang T;Ge P;Su Z;Ma W;Zhang R;Huang C;Li S;Lin D;Zhang J
缺氧与临床疾病有关。严重缺氧会导致多器官衰竭。然而，缺氧对大脑和内脏器官的不同影响仍需澄清，而且，缺氧易受损器官的特征仍然难以捉摸。在本研究中，我们首先旨在了解器官的缺氧敏感性。成年雄性小鼠暴露于6%O2或8%O2中6 h。对照小鼠在常氧条件下饲养。抗HIF-1α-NMS-cy 5.5纳米复合物的体内和体外成像显示，缺氧诱导因子（HIF-1α）在肝脏中的表达水平最高，其次是肾脏和脑。HIF-1α表达于肝细胞、肾远曲小管和大脑皮质神经元。肝脏、肾脏和大脑显示出不同的代谢特征，但谷氨酸的变化相同。与肾脏和大脑相比，肝脏具有更多的特征性代谢产物，并且与多巴胺解和糖酵解相关的代谢途径受到更多的干扰。缺氧小鼠脑组织中O-磷酸胆碱、GTP、NAD和天冬氨酸水平均显著升高，与对照组小鼠的自主活动呈显著正相关，但与缺氧损伤小鼠的自主活动无显著相关性。肝、肾、脑是机体对急性缺氧反应最强烈的三大器官，其中肝脏的缺氧敏感性最高。代谢紊乱似乎是生理功能变化的基础。
Hypoxia is associated with clinical diseases. Extreme hypoxia leads to multiple organs failure. However, the different effects of hypoxia on brain and visceral organs still need to be clarified, and moreover, characteristics in vulnerable organs suffering from hypoxia remain elusive. In the present study, we first aimed to figure out the hypoxic sensitivity of organs. Adult male mice were exposed to 6% O2 or 8% O2 for 6 h. Control mice were raised under normoxic conditions. In vivo and in vitro imaging of anti-HIF-1α-NMs-cy5.5 nanocomposites showed that the expression level of hypoxia-inducible factor (HIF-1α) was the highest in the liver, followed by kidney and brain. HIF-1α was detected in the hepatocytes of liver, distal convoluted tubules of kidney and neurons of cerebral cortex. The liver, kidney and brain showed distinct metabolic profiles but an identical change in glutamate. Compared with kidney and brain, the liver had more characteristic metabolites and more disturbed metabolic pathways related to glutaminolysis and glycolysis. The level of O-phosphocholine, GTP, NAD and aspartate were upregulated in hypoxic mice brain, which displayed significant positive correlations with the locomotor activity in control mice, but not in hypoxic mice with impaired locomotor activities. Taken together, the liver, kidney and brain are the three main organs of the body that are strongly respond to acute hypoxia, and the liver exhibited the highest hypoxic sensitivity. The metabolic disorders appear to underlie the physiological function changes.
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影响因子：
62.1
作者：
Chipot C;Dehez F;Schnell JR;Zitzmann N;Pebay-Peyroula E;Catoire LJ;Miroux B;Kunji ERS;Veglia G;Cross TA;Schanda P
通讯作者：
Schanda P
影响因子：
3.7
作者：
Chhabra V;Anand AS;Baidya AK;Malik SM;Kohli E;Reddy MPK
通讯作者：
Reddy MPK
影响因子：
3.4
作者：
Hurtado-Arestegui, Abdias;Plata-Cornejo, Raul;Pando, Jackelina
通讯作者：
Pando, Jackelina
影响因子：
0.9
作者：
Bouak, Fethi;Vartanian, Oshin;Cheung, Bob
通讯作者：
Cheung, Bob
影响因子：
64.8
作者：
KANAI, Y;HEDIGER, MA
通讯作者：
HEDIGER, MA