%0 Journal Article
%T Polymyxin B Alleviates Angiotensin II-Induced Stress Fiber Formation and Cellular Hypertrophy
%A Kwang-Seok Oh
%A Jeong Hyun Lee
%A Byung Koo Oh
%A Jihye Mun
%A Byung Kil Park
%A Byung Ho Lee
%J Pharmacology & Pharmacy
%P 903-910
%@ 2157-9431
%D 2014
%I Scientific Research Publishing
%R 10.4236/pp.2014.59101
%X <p style=\"text-align:justify;\">
	<span style=\"font-size:10.0pt;font-family:&quot;\"><span style=\"font-family:Verdana;\">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
¦ÌM) significantly inhibited stress fiber formation induced by angiotensin II
(Ang II) in rat heart-derived H9c2 cells. Furthermore, polymyxin B (1 - 10 ¦ÌM)
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, GSK3</span><i><span style=\"font-family:Verdana;\">¦Â</span></i><span style=\"font-family:Verdana;\">, MLCK, PKC, PKD2, AMPK, ROCK2, p70S6K,
SGK1were evaluated. Polymyxin B possesses a potent G protein related kinase 5
(GKR5) inhibitory activity with IC</span><sub><span style=\"font-family:Verdana;\">50</span></sub><span style=\"font-family:Verdana;\"> value of 1.1 ¦ÌM, 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.</span></span>
</p>
%K Polymyxin B
%K GRK5
%K Angiotensin II
%K Actin Stress Fiber
%K Cellular Hypertrophy
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=48964