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

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DOI: 10.4236/pp.2014.59101    3,535 Downloads   4,016 Views  

ABSTRACT

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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Oh, K. , Lee, J. , Oh, B. , Mun, J. , Park, B. and Lee, B. (2014) Polymyxin B Alleviates Angiotensin II-Induced Stress Fiber Formation and Cellular Hypertrophy. Pharmacology & Pharmacy, 5, 903-910. doi: 10.4236/pp.2014.59101.

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