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- W2078299214 abstract "Purpose: Sigma-1 receptor (Sig-1R) has no known homology with any other receptors. Natural ligands are yet to be identified. Sig-1R appears to play a critical role in controlling cell proliferation. The human lens grows throughout life and uncontrolled growth after cataract surgery is responsible for Posterior Capsule Opacification (PCO). We have therefore investigated a possible role for Sig-1R antagonists in controlling PCO.Methods: The human lens cell line FHL124 expresses the Sig-1R and was employed for this study. Cells were maintained in EMEM or EMEM supplemented with 5% Serum (FCS) at 35°C in 5% CO2. Sig-1R siRNA and scrambled siRNA were purchased from Ambion. Cell growth was assessed by measuring total protein and cell death by quantifying LDH leakage. mRNA level was assayed by RT-PCR. Protein level was measured by western blotting.Results: A dose-dependent effect of Sig-1R antagonist (rimcazole or BD1047) on cell growth was observed. 72 hours of transfection with siRNAs directed against Sig-1R reduced mRNA and protein levels by over 70 and 60% respectively. Subsequent incubation for 96 hours in 5%FCS gave a partial recovery of mRNA, but no significant increase in protein expression. LDH leakage assays showed that significant cell death occurred and was accompanied by an increased level of Caspase-3. The increases of pERK and pAkt stimulated with 10nM thrombin were inhibited by silencing Sig-1R, but not in cells exposed to scrambled siRNA. The recycling level of EGF receptor was significantly reduced by Sig-1R antagonists compared with controls.Conclusions: This study establishes a central role for the Sig-1R in lens cell survival through modulating the activity of growth factor receptor mediated cell signalling and growth factor receptor trafficking." @default.
- W2078299214 created "2016-06-24" @default.
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- W2078299214 date "2007-10-02" @default.
- W2078299214 modified "2023-09-24" @default.
- W2078299214 title "Sigma-1 receptor: a pivotal role in lens cell survival" @default.
- W2078299214 doi "https://doi.org/10.1111/j.1600-0420.2007.01063_3310.x" @default.
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