HIF-1α contributes to hypoxia adaptation of the naked mole rat.
HIF-1α contributes to hypoxia adaptation of the naked mole rat.
复制标题
HIF-1α有助于裸鼹鼠的缺氧适应
DOI：
10.18632/oncotarget.22767
复制
发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Cui S
中科院分区：
文献类型：
--
作者：
Xiao B;Wang S;Yang G;Sun X;Zhao S;Lin L;Cheng J;Yang W;Cong W;Sun W;Kan G;Cui S
裸鼹鼠（NMR）的生活在洞穴系统中含有非常低的氧气水平，表明长期缺氧暴露，并表明缺氧引起的病理变化减弱或不存在于这种缺氧耐受物种。NMR耐缺氧的机制仍然知之甚少。本研究旨在探讨缺氧诱导因子1α（HIF-1α）和血管内皮生长因子A（VEGFA）在核反应器缺氧适应中的作用。用50 μM YC-1、50 μM KC 7 F2或VEGFA siRNA处理从NMR和小鼠分离的原代肝星状细胞（HSC）。Western blot和real-time PCR检测HIF-1α和VEGFA的表达。流式细胞术检测细胞凋亡。Western blot检测自噬标志物LC 3和p62的表达。结果表明，NMRs中HIF-1α和VEGFA的表达明显高于缺氧敏感小鼠。缺氧后抑制HIF-1α表达可诱导NMR和小鼠HSC凋亡。然而，阻断VEGFA转录导致缺氧前后NMR和小鼠HSC凋亡的显著增加。此外，在缺氧条件下，NMR HSC显示出比小鼠HSC（LC 3 III/LC 3 II的相对比率= 4.9）更高水平的自噬（LC 3 III/LC 3 II的比率= 9.6）。提示HIF-1α的激活可能是低氧适应的重要机制。然而，在NMR中，VEGFA的高表达伴随着HIF-1α的激活。
Naked mole rats (NMRs) spend their lives in burrow systems containing very low levels of oxygen, indicating long-term hypoxic exposure, and suggesting that pathological changes caused by hypoxia are attenuated or absent in this hypoxia-tolerant species. The mechanisms underlying NMRs hypoxia tolerance remain poorly understood. In this study, we explored whether hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) play a role in NMRs adaption to hypoxia. Primary hepatic stellate cells (HSCs) isolated from NMRs and mice were treated with 50 μM YC-1, 50 μM KC7F2 or VEGFA siRNA. HIF-1α or VEGFA expression was detected by Western blot and real-time PCR. Apoptosis was determined by flow cytometry. The expression of autophagy markers (LC3 and p62) was detected by Western blot. Our results showed that HIF-1α and VEGFA expression in NMRs was significantly higher than in hypoxia-sensitive mice. Inhibition of HIF-1α expression induced apoptosis in both NMR and mouse HSCs following hypoxia. However, blocking VEGFA transcription results in a significant increase of apoptosis in both NMR and mouse HSCs before and after hypoxia. In addition, NMR HSCs displayed higher levels of autophagy (ratio of LC3ΙΙ/LC3Ι = 9.6) than mouse HSCs (relative ratio of LC3ΙΙ/ LC3Ι = 4.9) under hypoxic conditions. We conclude that HIF-1α activation may be an important mechanism for hypoxia adaption. However, high expression of VEGFA follows HIF-1α activation in NMRs.
登录
查看更多内容
DOI：
10.1073/pnas.93.18.9493
发表时间：
1996-09-03
影响因子：
11.1
作者：
Hochachka, PW;Buck, LT;Land, SC
通讯作者：
Land, SC
DOI：
10.1098/rspb.2014.1722
发表时间：
2015-02-07
影响因子：
4.7
作者：
Pamenter, Matthew E.;Dzal, Yvonne A.;Milsom, William K.
通讯作者：
Milsom, William K.
DOI：
10.1073/pnas.0403540101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Shams, I;Avivi, A;Nevo, E
通讯作者：
Nevo, E
影响因子：
3.7
作者：
Herculano-Houzel S
通讯作者：
Herculano-Houzel S
DOI：
10.1007/s00335-016-9648-5
发表时间：
2016-08
期刊：
Mammalian genome : official journal of the International Mammalian Genome Society
影响因子：
--
作者：
Lewis KN;Soifer I;Melamud E;Roy M;McIsaac RS;Hibbs M;Buffenstein R
通讯作者：
Buffenstein R