PKB/Akt regulates the aggregation of actin by Girdin in mouse fertilized eggs / 生物工程学报

The purpose of this study is to reveal the role of Girdin in regulating the aggregation of actin filaments by studying the relationship between PKB/Akt and Girdin. First we used Scansite software (http://scansite.mit.edu) to predict relevant target sites of PKB/Akt on mouse Girdin. To gain insight into the role of phosphorylation of Girdin by PKB/Akt, we assessed the location of phosphorylated Girdin in fertilized eggs by staining with anti-P-Girdin 1 417 Ab. We detected a distinct increase in the fluorescence signal of F-actin and P-Girdin 1 417 after microinjection of Akt WT and myr-Akt. The addition of myr-Akt induced phosphorylation of Girdin in mouse fertilized eggs. In addition, siRNA-mediated Akt-knockdown blocked phosphorylation of Girdin. The distribution of actin filaments was obviously scattered. These results strongly suggest that PKB/Akt could directly phosphorylate Girdin on Ser1 417 and promote its function in mouse fertilized eggs.

Analgesia effects of intrathecally coadministered dexamethasone and Alt inhibitors on chronic dorsal root ganglion compression-induced pain in mouse / 中华行为医学与脑科学杂志

Objective To investigate the analgesic effects of intrathecal dexamethasone injection on pain induced by chronic compression of dorsal root ganglion in mouse.Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion ( CCD), 40 male SD rats successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into 5 groups:Sham-operation group ( Sham group, n = 8 ), Control group ( CCD group, n = 8), Dexamethasone group ( D group, n = 8), Akt inhibitor V group (A group, n = 8 ) and Dexamethasone plus Akt inhibitor Ⅳ group (DA group, n = 8 ).Rats in D group, A group or DA group were intrathecally treated with dexamethasone (100μg/kg) ,Akt inhibitor Ⅳ (0.6μg/10μl) or dexamethasone ( 100 μg/kg) plus Akt inhibitor Ⅳ (0.6 μg/10 μl) on Day 3,13 after CCD respectively, while rats in C and Sham group received Vehicle (10% DMSO).Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested on 3 d before and 3 d,4 d,7 d,10 d,13 d,14 d and 15 d after operation.Results Compared with Sham group,both PWMT (P＜0.01) and PWTL (P＜0.01) were significantly decreased after CCD surgery on the ipsilateral side.After dexamethasone and Akt inhibitor were respectively intrathecally injected at 3 postoperative day,PWMT (7.33 ± 1.03 ) g, (5.67 ± 1.03 ) g, (2.67 ± 1.03 ) g (P ＜0.01 ) ,PWTL( 16.47 ±0.46)s, ( 14.48 ±0.84) s, ( 10.82 ±2.21 ) s(P＜0.01 ) ,then decreased gradually,and intrathecally injected again at 13 postoperative day, PWMT ( 7.33 ± 1.03 ) g, ( 5.67 ± 1.03 ) g, (2.33 ± 0.81 ) g (P ＜0.01 ), PWTL( 16.44 ±0.90) s, ( 14.01 ±0.82)s, ( 10.22 ± 1.28)s (P＜0.01).Coadministration dexamethasone and Akt inhibitor exhibit significant synergies, postoperative 4 d PWMT( 10.83 ± 2.04)g, (2.67 ± 1.03 )g (P ＜0.01),PWTL(19.11 ±2.01)s,(10.82 ±2.21)s (P＜0.01);14 d PWMT (7 ±0.82)g,(2.33 ±0.81)g (P ＜ 0.01 ), PWTL( 17.16 ± 1.14)s, ( 10.22 ± 1.28 ) s (P ＜ 0.01 ).Conclusion Intrathecal high-dose dexamethas one or PKB / Akt inhibitors can effectively improve pain behavior response induced by chronic compression of dorsal root ganglia,combination of these two drugs could generate significant synergies, and the effection is more obvious, more durable.