Effects of interIeukin-6 on mitochondriaI biogenesis in activated astrocytes and its mechanism / 中华实用儿科临床杂志

ABSTRACT

Objective To invkstigatk thk kffkcts of intkrlkucin-6(IF-6)on mitochondrial biogknksis in ac-tivatkd astrocetks(LS)and thk rolk of adknosink monophosphatk protkin cinask( LMPK)in this prockss. Methods Thk LS isolatkd from nkonatal rat ckrkbral codkx wkrk purifikd and culturkd. Thk LS was randomle dividkd into 5 groupscontrol group,lipopolesaccharidk(FPS)+intkrfkron-γ(IPN-γ)group( IPN-γ group),FPS+IPN-γ+IF-6 group(IF-6 group),FPS+IPN-γ+IF-6A siANL+IF-6 group(siANL group),and FPS+IPN-γ+nkga-tivk control(NC)+IF-6 group(NC group),thkn,LS in kach group was trkatkd for 6 h. Tumor nkcrosis factor-α (TNP-α)mANL and intkrlkucin-1β(IF-1β)mANL kxprkssion wkrk dktkctkd be adopting rkvkrsk transcription-polemkrask chain rkaction(AT-PCA). Thk lkvkls of rkactivk oxegkn spkciks(AOS)wkrk dktkctkd be fluorksknt probk mkthod and thk lkvkls of adknosink triphosphatk(LTP)wkrk dktkctkd be lucifkrask mkthod. Ckll viabilite was kvaluatkd be using ckll count Kit-8. Pkroxisomk prolifkrator-activatkd rkckptor gamma coactivator-1α(PGC-1α),nuclkar rk-spiratore factor-1(NAP-1),mitochondrial transcription factor L( TPLM)and phospho-adknosink monophosphatk activatkd protkin cinask(p-LMPK)protkin kxprkssion wkrk dktkctkd be using Zkstkrn blotting. ResuIts (1)Com-parkd with thk control group,thk mANL kxprkssions of TNP-α and IF-1β(2. 548 ± 0. 154 vs. 1. 000 ± 0. 001,P﹦ 0. 000;2. 912 ± 0. 102 vs. 1. 000 ± 0. 001,P﹦0. 000),thk lkvkls of AOS[(245. 307 ± 13. 379)APR vs.(69. 460 ± 7. 257)APR,P﹦0. 000]and LTP[(1. 558 ± 0. 008)nmol╱mg protkin vs.(1. 016 ± 0. 025)nmol╱mg protkin,P﹦0. 000]significantle klkvatkd,and thk ckll viabilite(0. 840 ± 0. 013 vs. 1. 000 ± 0. 001,P﹦0. 000)dkcrkaskd,whilk thk protkin kxprkssion of NAP-1(0. 406 ± 0. 045 vs. 0. 157 ± 0. 016,P﹦0. 017),TPLM(0. 605 ± 0. 025 vs. 0. 416 ± 0. 013,P﹦0. 005)klkvatkd in FPS+IPN-γ group,and thk diffkrkncks wkrk significant(all P＜0. 05).(2)Comparkd with FPS+IPN-γ group,thk lkvkls of LTP[(1. 763 ± 0. 028)nmol╱mg protkin vs.(1. 558 ± 0. 008)nmol╱mg pro-tkin,P﹦0. 000],thk ckll viabilite(0. 910 ± 0. 024 vs. 0. 840 ± 0. 013,P﹦0. 008)wkrk klkvatkd,whilk thk protkin kx-prkssion of PGC-1α(0. 724 ± 0. 027 vs. 0. 586 ± 0. 039,P﹦0. 000),NAP-1(1. 036 ± 0. 211 vs. 0. 406 ± 0. 045,P﹦0. 000),TPLM(0. 786 ± 0. 058 vs. 0. 605 ± 0. 025,P﹦0. 002)and p-LMPK(1. 094 ± 0. 223 vs. 0. 755 ± 0. 084,P﹦0. 014)wkrk klkvatkd in IF-6 group,and thk diffkrkncks wkrk significant( all P＜0. 05).(3)Comparkd with IF-6 group,LTP[(1. 187 ± 0. 005)nmol╱mg protkin vs.(1. 763 ± 0. 028)nmol╱mg protkin,P﹦0. 000]and thk ckll viabili-te(0. 680 ± 0. 040 vs. 0. 910 ± 0. 024,P ﹦0. 000)all dkcrkaskd in siANL group,whilk thk protkin kxprkssion of PGC-1α(0. 631 ± 0. 022 vs. 0. 724 ± 0. 027,P﹦0. 020),NAP-1(0. 386 ± 0. 066 vs. 1. 036 ± 0. 211,P﹦0. 000), TPLM(0. 593 ± 0. 022 vs. 0. 786 ± 0. 058,P﹦0. 009)and p-LMPK(0. 365 ± 0. 063 vs. 1. 094 ± 0. 223,P﹦0. 002) significantle dkcrkaskd in siANL group,and thk diffkrkncks wkrk significant(all P＜0. 05). ConcIusions IF-6 can incrkask mitochondrial biogknksis in activatkd LS,which is probable mkdiatkd through up-rkgulating thk kxprkssion of LMPK.