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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Aminoquinolines, Blotting, Western, Cells, Cultured, Down-Regulation, Gene Expression Regulation, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Immunoenzyme Techniques, Pyrimidines, RNA, Messenger, Retinal Pigment Epithelium, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, rac1 GTP-Binding Protein.
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Does rac1 activate HIF-1 in retinal pigment epithelium cells under hypoxia? Context: 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-1alpha 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-1alpha are largely unknown. Rho family small GTPase Rac1, as a potential intermediate, possibly plays a pivotal role in activating HIF-1alpha in RPE cells under hypoxia. To further define Rac1 playing an essential role in the induction of HIF-1alpha expression in RPE cells under hypoxia. In this study, we examined the expression of HIF-1alpha 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-1alpha, 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-1alpha and Rac1 measured by RT-PCR and Western blot. The mRNA expression of HIF-1alpha and Rac1 in RPE cells significantly increased in a time-dependent manner, reaching the maximum at 4 h, and thereafter slowly declined. HIF-1alpha 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-1alpha and Rac1 expression were significantly inhibited in hypoxic RPE cells.
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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. Final Decision: yes