Polymyxin B Alleviates Angiotensin II-Induced Stress Fiber Formation and Cellular Hypertrophy

• 作者: Byung Ho Lee Byung Kil Park Byung Koo Oh Jeong Hyun Lee Jihye Mun Kwang-Seok Oh
• 来源期刊: 药理与制药(英文)
• 学科: 医学
• 关键词: POLYMYXIN B GRK5 ANGIOTENSIN II ACTIN Stress FIBER CELLULAR HYPERTROPHY
• 年，卷（期）: 2014,（9）
• 页码范围: 903-910
• 页数: 8页
• 分类号: R73

摘要

Polymyxin B is widely used antibiotic in the clinic for resistant Gram-negative infections. In addition, polymyxin B-immobilized hemoperfusion cartridge has been used for endotoxin removal therapy in patients with septic shock. The aim of this study was to investigate the anti-fibrotic and anti-cellular hypertrophic effects of polymyxin B, and further to explore its possible mechanism. Polymyxin B (3, 10 μM) significantly inhibited stress fiber formation induced by angiotensin II (Ang II) in rat heart-derived H9c2 cells. Furthermore, polymyxin B (1 - 10 μM) showed a potent inhibitory effect on Ang II-induced cellular hypertrophy in H9c2 cells. Under the mechanism study, the inhibitory activities of polymyxin B against kinases involved in cellular hypertrophy such as AKT1, CAMK, GRK5, GSK3β, MLCK, PKC, PKD2, AMPK, ROCK2, p70S6K, SGK1were evaluated. Polymyxin B possesses a potent G protein related kinase 5 (GKR5) inhibitory activity with IC50 value of 1.1 μM, and has an ATP non-competitive inhibitory mode. Taken together, these results indicate that polymyxin B alleviates Ang II-induced stress fiber formation and cellular hypertrophy, and propose that one mechanism underlying these effects involves inhibition of the GRK5 pathway.