Beta-adrenergic agonist protects retinal pigment epithelium against hydroxycholoroquine toxicity via c AMP-PKA signal pathway

• 作者: Dan-Ning Hu Richard Rosen Ruihua Zhang
• 来源期刊: 国际眼科杂志:英文版
• 学科: 医学
• 关键词: hydroxycholoroquine RETINAL PIGMENT epithelial cells RETINOPATHY protein kinase A VACUOLATION
• 年，卷（期）: 2020,（4）
• 页码范围: 552-559
• 页数: 8页
• 分类号: R59

摘要

AIM: To test our hypothesis that activation of protein kinase A(PKA) signal pathway by β-adrenergic agonist plays an important role in the protecting of cultured retinal pigment epithelial(RPE) cells against the hydroxychloroquine(HCQ) toxicity. METHODS: Cultured human RPE cells were treated with 1) HCQ, 2) HCQ with salbutamol(a β2-adrenergic receptor agonist), and 3) HCQ with salbutamol and a PKA inhibitor, and compared these to 4) untreated cells(controls). After treated for 24 h, cell vacuolation, cells viability, PKA and PKA kinase activity levels were determined by the measurement of the size of vacuoles using Image J software, the cell counting with a dye-exclusion testing, Western blot and PKA kinase detection, respectively. RESULTS: Cell vacuolation and cell death of cultured RPE cells were significantly increased by the treatment of HCQ. Salbutamol significantly elevated PKA and PKA activity levels and this was associated with the inhibition of the vacuolation and cell death. The PKA inhibitor significantly decreased the PKA levels and eliminated the protective effects of salbutamol on HCQ-treated RPE cells. CONCLUSION: The PKA pathway plays an important role in the protective effects of β2-adrenergic agonist on the RPE cells against HCQ toxicity. These findings reveal a novel potential strategy against HCQ retinopathy by treatment with PKA activating medications.