Heat shock protein 90 is involved in regulation of hypoxia-driven proliferation of embryonic neural stem/progenitor cells.
Hypoxia may regulate the proliferation of diverse stem cells. Our previous study showed that hypoxia promoted the proliferation of embryonic neural stem/progenitor cells (NPCs) and that hypoxia inducible factor-1(HIF-1) was critical in this process. HIF-1 could be stabilized under hypoxic conditions, and heat shock protein 90 (HSP90) is an essential protein that controls the activity and stabilization of HIF-1alpha. In the present work, we investigate whether HSP90 is involved in proliferation of NPCs under hypoxia by regulating HIF-1alpha stabilization. Geldanamycin (GA), an HSP90 inhibitor, decreased the expression of HIF-1alpha in NPCs during hypoxia-driven proliferation and reduced the expression level of HIF-1alpha protein under hypoxia in a time-dependent manner. The proliferation of NPCs induced by hypoxia was inhibited after GA treatment for 24 h. Another HSP90 inhibitor, radicicol, had the same effect on NPCs as GA. Furthermore, the expression of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in NPCs under hypoxia was suppressed by GA. The above data indicated that HSP90 might be involved in regulation of hypoxia-driven proliferation.
Xiong
Lei
L
College of Life Science, Wuhan University, Wuhan, People's Republic of China.
Zhao
Tong
T
Huang
Xin
X
Liu
Zhao-hui
ZH
Zhao
Hua
H
Li
Ming-ming
MM
Wu
Li-ying
LY
Shu
Hong-bing
HB
Zhu
Ling-ling
LL
Fan
Ming
M
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003720:Densitometry; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047029:Lactams, Macrocyclic; D018942:Macrolides; C035359:monorden; C001277:geldanamycin