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J Biol Chem. 2007;282(42):30901-30909. 2.Mei Y, Yuan Z, Song B, Li D, Ma C, Hu C, Ching YP, Li M. Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience. 2008;151(3):771-779. 3.Wang W, Yang Y, Ying C, Li W, Ruan H, Zhu X, You Y, Han Y, Chen R, Wang Y, Li M. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology. 2007;52(8):1678-1684. 4& & tZZZt"""  E Cv KRB YF  ;- : vch(Pi Rongbiao) 33\ ZSXf[MO ^02002t^kNN-Nq\'Yf[ ^y~otf[ZSX0 Tt^t/nyb'Yf[uirSf[|NNZSXTxvz s(W-Nq\'Yf[of[bN^0;NxvztQmS^y~Oboirv\O(uSvQ:g6Rvxvz0f#bSRSbV[6qyf[WёI{Yyxvz0]Shb_ShWя20{ vQ-NSCIe5{0 vZSXN,gNT\O11t^ gqQ TvxvzT \O:NqQ T\OShY{SCIe0NccN,gyvmSv'YR[elTb/g $\vQ(Wzuk}SOg^eby/}N~ez 0;N#zuk}SOg^I{]\O0 ShvvsQe 1. Rongbiao Pi, Wenming Li, Nelson T.K.Lee, Hugh H.N.Chan, Yongmei Pu, Ling Nga Chan, Nikolaus J. Sucher, Doanld C. Chang, Mingtao Li and Yifan Han. Minocycline prevents glutamate-induced apoptosis of cerebellar granule neurons by differential regulation of p38 and Akt pathways. J Neurochem. 2004, 91:1212-1230. 2. & & 3. & & f/oU  nL$  ) 7 /qr=C3uyv TLċaSO  $ ΞfmHQu `}Y`3uvyv~N[bhyhQ TaDR0sQN`Ovyvv TLċaY N 1. ,gyv(W\|~ހdvySOQN!jW-N SsNNyvcBimvelU_VP[SP1 3uNՋVǑ(uzuklgb/g0WVzSNSRP[uirf[elۏNekSP1/fvccbimWVvُNGP0zywQ gMR'` 3uN]\OW@x}Y v^NVEmory'Yf[0/n'Yf[ ggvT\OagN [hQY[b,gy0^OHQDR0 2. ,gyvzyOnc:NEQR wQ gN[vf[/gReSyf[aIN0xvzQ[fnx0b/g~npf0xvzelTeHhSL03u gؚvf[/g4ls^ NSY!k;NcV[6qyf[Wёv~0 Te 3u@b(WUSMOS gk}Yv[[SagN0^~NDR0 3. xvzwQ g}Yv]\OW@x xvzwQ gؚvf[/gN

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(A) Mithramycin A attenuates the upregulation of BimEL induced by activity deprivation in a dose dependent manner. CGNs were placed in 25K or 5K media in the absence or presence of mithramycin A at the indicated concentrations for 6 h. BimEL expression was assessed by Western blot as described in Fig.1(A). Results shown are representative of four separate experiments. (B) Mithramycin A inhibits the increase in bim mRNA level in a dose-dependent manner. Neurons were treated as described in (A), bim and actin mRNAs were determined by RT-PCR, Results shown are representative of five separate experiments. (C) Mithramycin A suppresses the activation of bim promoter induced by activity deprivation. Neurons were co-transfected with bim-Luc and pEF-RL for 8 hr. Luciferase activities were measured as described in Fig.2, The experiments were repeated three times with duplicates for each treatment. 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B  ZgֳgֳDo?" @ "   `gֳgֳ?#" `y0i@$ 0$ 0H  0޽h ? f3f3y___PPT10Y+D=' = @B +  0 t(  x  c $8 d 8   Zgֳgֳ?#" `Uzj@$ 0$ 0  Zgֳgֳ?#" `S  @$ 0$ 0  NL8gֳgֳ ?" d xvzeHh*(lP, H  0޽h ? f3f3y___PPT10Y+D=' = @B +m  0 $(  r  S 88 P  8 r  S 8  8 H  0޽h ? f3f3y___PPT10Y+D=' = @B +  0 (  r  S 8 pR  8 H  0޽h ? f3f3y___PPT10Y+D=' = @B +  0 (  r  S o   H  0޽h ? f3f3y___PPT10Y+D=' = @B + 0 (    N`A ??   B8+z Zyv~;NbXTG( H  0޽h ? f3f3y___PPT10Y+D=' = @B + 0 (  ~  BA ??   Bt8i V ~93uhG( H  0޽h ? f3f3y___PPT10Y+D=' = @B +u  0   ,(   r   S 8   8 r   S x8 p  8 8 @/  /@B   ZgֳgֳDo?"@ @B   ZgֳgֳDo?" # B   ZgֳgֳDo?"`  B   ZgֳgֳDo?"@) 0 B   ZgֳgֳDo?"P B   ZgֳgֳDo?"//H   0޽h ? f3f3y___PPT10Y+D=' = @B +E  0 \T0(  r  S l8   8 r  S 8  8 B  ZgֳgֳDo?"jB  ZgֳgֳDo?"  B  ZgֳgֳDo?"IIH  0޽h ? f3f3___PPT10i.O;+D=' = @B +  0 @r(  r  S  < w  < B  ZgֳgֳDo?") " ) B  ZgֳgֳDo?" B  ZgֳgֳDo?"ZH  0޽h ? f3f3___PPT10i. U+D=' = @B +m  0 P<$(  <r < S +<   < r < S &< " < H < 0޽h ? f3f3y___PPT10Y+D=' = @B +  0 (  x  c $G<   < x  c $H< p <   0"`0@0@$ 0$ 0  0"`P @M$ 0$ 0  Zgֳgֳ?#" `` P @$ 0$ 0H  0޽h ? f3f3y___PPT10Y+D=' = @B +  0 (  r  S @Y<  < H  0޽h ? f3f3___PPT10i.p`<+D=' = @B +  0  (   r   S q< =Z < H   0޽h ? f3f3___PPT10i.pPB+D=' = @B + 0  X(  j  6p<@0  . NAmNT\O bNNVE TL^zNo}YvNAm nS NkP[e(Zixu Mao, Associate Professor Brown University s(WEmory University)0!`Q(Yifan Han, Associate Professor Hong Kong University of Science and Technology)NvOc[RT\OsQ| bN]~qQ TShNY{SCIe]\OW@x-NvSe.s (WNXT0Oo`0ՋBRT}SOI{YebwckZP0RNNTN`0,gN\dkƉ:N[b,gyvv[5agNKNN0  sG/>'/@"  0"` @0$ 0$ 0H  0޽h ? f3f3y___PPT10Y+D=' = @B + 0 "Pd(  dx d 6T<29   Re/fupB /fċT&TybQvsQ. Ref[/gRe ``Re evt evel evSO| evĉ_ n4YReSY'` /UN'` n4Y gۏNekSU\vMRof0w_2< w_20w_2g G,G;Gg G g Gg o d N<gֳgֳ ?"  n R e '`.(lP2G,H d 0޽h ? f3f3y___PPT10Y+D=' = @B +A 0 h ` ` h (  h h <<r X&,gyvvyrrNRe 3uN!kbSN^y~CQQNeOQNˆ}vBim N/f NOVNJNK/c-Jun(Leyu Shi,et al, Neurosci Lett. 2005)N‰[KNT SNS`v[~gfPI3K/Akt/FKHRL1OS_N NSNbimv NzyOnc 0 bim NvlU_:g6R/fNHNbNsHQ[bim/TRP[ۏLN5 +gz^R~QRg nxzN[bimhv/TRP[8h_:S ۏ SsN*NxQWvlU_VP[SP1~T^RMONvQ-N0ۏNek[>f:y^y~CQQNeSP1o;m>f'`SP1zSSOTSP1-DNA~Tb6RBRmithramycin ASb6Rbimv N09hncN NuirOo`f[RgT[‰[ bN!kcQNSP1N[bim NُNevbimlU_:g6R^y~CQQNelU_VP[SP1o;m o;mvSP1Nbim/TRP[8h_:SvSP1~T^R~T N lU_o;mbimvh0 ,gyvbۏNekǑ(u>f'`SP1zSSOvzukhb/gNS/TRP[pzS0EMSATCHIPel e(W_SP1vccbimWVvS`nc :NfSP1[OQNˆ}vBimvc\O(uT:g6Rv^ۏNeknxzSP1\O:N^y~L'`uuluvevpcOfEQRvyf[Onc0 l Z Z         B h  `gֳgֳDo?"mz Z mB h  `gֳgֳDo?"* B h  `gֳgֳDo?" B h  `gֳgֳDo?"  B h  `gֳgֳDo?" 5B h  `gֳgֳDo?"<B  h  `gֳgֳDo?"P [P B  h  `gֳgֳDo?" 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J Biol Chem. 2007;282(42):30901-30909. 2.Mei Y, Yuan Z, Song B, Li D, Ma C, Hu C, Ching YP, Li M. Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience. 2008;151(3):771-779. 3.Wang W, Yang Y, Ying C, Li W, Ruan H, Zhu X, You Y, Han Y, Chen R, Wang Y, Li M. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology. 2007;52(8):1678-1684. 4& & tZZZt"""  E Cv KRB YF  ;- : vch(Pi Rongbiao) 33\ ZSXf[MO ^02002t^kNN-Nq\'Yf[ ^y~otf[ZSX0 Tt^t/nyb'Yf[uirSf[|NNZSXTxvz s(W-Nq\'Yf[of[bN^0;NxvztQmS^y~Oboirv\O(uSvQ:g6Rvxvz0f#bSRSbV[6qyf[WёI{Yyxvz0]Shb_ShWя20{ vQ-NSCIe5{0 vZSXN,gNT\O11t^ gqQ TvxvzT \O:NqQ T\OShY{SCIe0NccN,gyvmSv'YR[elTb/g $\vQ(Wzuk}SOg^eby/}N~ez 0;N#zuk}SOg^I{]\O0 ShvvsQe 1. Rongbiao Pi, Wenming Li, Nelson T.K.Lee, Hugh H.N.Chan, Yongmei Pu, Ling Nga Chan, Nikolaus J. Sucher, Doanld C. 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J Biol Chem. 2007;282(42):30901-30909. 2.Mei Y, Yuan Z, Song B, Li D, Ma C, Hu C, Ching YP, Li M. Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience. 2008;151(3):771-779. 3.Wang W, Yang Y, Ying C, Li W, Ruan H, Zhu X, You Y, Han Y, Chen R, Wang Y, Li M. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology. 2007;52(8):1678-1684. 4& & tZZZt"""  E Cv KRB YF  ;- : vch(Pi Rongbiao) 33\ ZSXf[MO ^02002t^kNN-Nq\'Yf[ ^y~otf[ZSX0 Tt^t/nyb'Yf[uirSf[|NNZSXTxvz s(W-Nq\'Yf[of[bN^0;NxvztQmS^y~Oboirv\O(uSvQ:g6Rvxvz0f#bSRSbV[6qyf[WёI{Yyxvz0]Shb_ShWя20{ vQ-NSCIe5{0 vZSXN,gNT\O11t^ gqQ TvxvzT \O:NqQ T\OShY{SCIe0NccN,gyvmSv'YR[elTb/g $\vQ(Wzuk}SOg^eby/}N~ez 0;N#zuk}SOg^I{]\O0 ShvvsQe 1. Rongbiao Pi, Wenming Li, Nelson T.K.Lee, Hugh H.N.Chan, Yongmei Pu, Ling Nga Chan, Nikolaus J. Sucher, Doanld C. 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J Biol Chem. 2007;282(42):30901-30909. 2.Mei Y, Yuan Z, Song B, Li D, Ma C, Hu C, Ching YP, Li M. Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience. 2008;151(3):771-779. 3.Wang W, Yang Y, Ying C, Li W, Ruan H, Zhu X, You Y, Han Y, Chen R, Wang Y, Li M. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology. 2007;52(8):1678-1684. 4& & tZZZt"""  E Cv KRB YF  ;- : vch(Pi Rongbiao) 33\ ZSXf[MO ^02002t^kNN-Nq\'Yf[ ^y~otf[ZSX0 Tt^t/nyb'Yf[uirSf[|NNZSXTxvz s(W-Nq\'Yf[of[bN^0;NxvztQmS^y~Oboirv\O(uSvQ:g6Rvxvz0f#bSRSbV[6qyf[WёI{Yyxvz0]Shb_ShWя20{ vQ-NSCIe5{0 vZSXN,gNT\O11t^ gqQ TvxvzT \O:NqQ T\OShY{SCIe0NccN,gyvmSv'YR[elTb/g $\vQ(Wzuk}SOg^eby/}N~ez 0;N#zuk}SOg^I{]\O0 ShvvsQe 1. Rongbiao Pi, Wenming Li, Nelson T.K.Lee, Hugh H.N.Chan, Yongmei Pu, Ling Nga Chan, Nikolaus J. Sucher, Doanld C. 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