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- Title
Rac1 activates HIF-1 in retinal pigment epithelium cells under hypoxia.
- Authors
Peng Zhang; Xing Zhang; Xiaofeng Hao; Yusheng Wang; Yannian Hui; Haiyan Wang; Dan Hu; Jian Zhou
- Abstract
Abstract Background Upregulation of vascular endothelial growth factor (VEGF) in hypoxic retinal pigment epithelium (RPE) cells, mediated by hypoxia-inducible factor-1 (HIF-1) is responsible for choroidal neovascularization (CNV). HIF-1α is the inducible subunit of HIF-1, but the underlying mechanisms by which RPE cells sense a decrease in oxygen concentration and transduce this signal to HIF-1α are largely unknown. Rho family small GTPase Rac1, as a potential intermediate, possibly plays a pivotal role in activating HIF-1α in RPE cells under hypoxia. Aims To further define Rac1 playing an essential role in the induction of HIF-1α expression in RPE cells under hypoxia. Methods In this study, we examined the expression of HIF-1α and Rac1 in human RPE cells under hypoxia for 0, 1, 2, 4, 8, 12 and 24 h by RT-PCR and Western blot. To elucidate whether Rac1 is responsible for activating the expression of hypoxia-induced HIF-1α, human RPE cells were treated with Rac1 inhibitor NSC23766 under hypoxia for 0, 1, 2, 4, 8, 12 and 24 h, and expression of HIF-1α and Rac1 measured by RT-PCR and Western blot. Results The mRNA expression of HIF-1α and Rac1 in RPE cells significantly increased in a time-dependent manner, reaching the maximum at 4 h, and thereafter slowly declined. HIF-1α protein induction in human RPE cells was found after 1 h of hypoxia, reaching the maximum at 8 h, and then slowly declined. In response to hypoxia, the levels of Rac1 protein significantly increased, reaching the maximum at 4 h, and then slowly declined. After treatment with NSC23766, both HIF-1α and Rac1 expression were significantly inhibited in hypoxic RPE cells. Conclusions Rac1 is crucial to activate HIF-1 in RPE cells under hypoxia, which may be a novel target other than VEGF and HIF-1 in developing CNV inhibitors.
- Subjects
EPITHELIAL cells; HYPOXEMIA; VASCULAR endothelial growth factors; NEOVASCULARIZATION; WESTERN immunoblotting; CELLULAR signal transduction; GUANOSINE triphosphatase
- Publication
Graefe's Archive of Clinical & Experimental Ophthalmology, 2009, Vol 247, Issue 5, p633
- ISSN
0721-832X
- Publication type
Article
- DOI
10.1007/s00417-008-1031-0