Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199

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  • 8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199

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    N T @ E @ B G J Y G Y K T

    Xlk gbx`ytnj`oktgx`k tnjk no KTE A! flgbbkjv `b tgxnvxkndjgvx`f fkjjv

    Jknbgthn Lktbgbhks A` Ln Ygta Vl`-W`be Fg` J`be W`b B`fnjg Ygtxt`hek Okhkt`fn Vkvx`

    Y{dj`vlkh nbj`bk3 79 Mgp 4995

    Vyt`bekt Vf`kbfk!D{v`bkvv Mkh`g D"_" 4995

    Gdvxtgfx Uk tkyntx nb xlk tnjk no A! f{ttkbxv `b xlk

    mkflgb`vmv tke{jgx`be xlk ytnj`oktgx`nb no [MT 79?-97nvxkndjgvx f nvxknvgtfnmg fkjjv" Kjkfxtnylpv`njne`fgj

    gbgjpv`v vlnukh xlgx [MT 79?-97 fkjjv ytnh{fk tnd{vx

    A! f{ttkbxv xlgx fgb dk ylgtmgfnjne`fgjjp vkygtgxkh `bxn

    xun mgcnt fnmynbkbxv3 g K-8967-v{vfkyx`djk f{ttkbx*

    @K-8967* gbh g xkxtgkxlpjgmmnb`{m ,XKG)-v{vfkyx`djk

    fnmynbkbx* @XKG" Ukvxktb djnx gbh TX-YFT gbgjpv`v

    vlnukh xlgx @K-8967 `v ytnh{fkh dp kxlkt g en-en ,kge)-

    tkjgxkh flgbbkjv ,KTE)" @bf{dgx`nb no xlk fkjjv u`xl K-

    8967 kblgbfkh xlk`t ytnj`oktgx`nb dp

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    x{mnt fkjj j`bkv no h`ooktkbx vykf`kv ,l{mgb gbh m{t`bk)

    gbh h`vx`bfx l`vxnekbkv`v ,bk{tndjgvxnmg* tlgdhnmpnvgt-

    fnmg* ghkbnfgtf`bnmg* j{be m`ftnfpxnmg* y x{`xgtp

    x{mntv* `bv{j`bnmg dkxg-fkjjv* gbh mnbndjgvx`f jk{akm`g)

    Q;* ?* 79* 4;* 86* 8?* ;7]" Kkb xln{el ynxgvv`{m flgbbkjv

    gtk gd{bhgbx `b dnbk fkjjv* xlk`t tnjk `b hkxktm`b`be dnbk

    hkkjnymkbxg fnmyjk| ytnfkvv ul`fl `v tke{jgxkh dp

    m{jx`yjk ogfxntv `bfj{h`be lnmkndn| xtgbvft yx`nb ogfxntv*etnuxl ogfxntv ,OEO* _KEO* DMYv* @EO)* xtgbvft yx`nb

    ogfxntv ,T{b|4* Vn|)* lntmnbkv ,EL* YXL) mgxt`| mk-

    xgjjnytnxk`bgvkv* ytnxk`b a`bgvkv* `xgm`b H* vk| vxktn`hv

    gbh fgjf`{m Q77]`v ynntjp {bhktvxnnh" Xn kj{f`hgxk xlk

    tnjk no ynxgvv`{m flgbbkjv `b xlk mkflgb`vmv xlgx hkxkt-

    m`bk xlk ytnj`oktgx nb no dnbk x`vv{k uk flgtgfxkt`skh

    ynxgvv`{m f{ttkbxv k|ytkvvkh `b [MT 79?-97 nvxkndjgvx`f

    nvxknvgtfnmg fkjjv" Lktk uk vlnu xlgx `bl`d`x nb no

    kbhnekbn{v KTE flgbbkjv dp xlk fjgvv @@@ gbx`gttlpxlm`f

    fnmyn{bh* K-8967* jkghv xn g v`eb`fgbx `bftkgvk `b xlk

    ytnj`oktgx`nb no xlk fkjjv" Uk o{txlkt vlnu xlgx xlk m`xn-

    ekb`f kookfx no K-8967 `bnjkv xlk gfx`gx`nb no fgjf`{m-hkykbhkbx ygxlugpv xltn{el xlk `bl`d`x nb no xlk KTE

    flgbbkjv" Xgakb xnekxlkt xlkvk bh`bev {bhktvfntk bku

    tnjkv no KTE A! flgbbkjv `b dnbk x`vv{k fkjjv gbh ytn`hk

    gb {bk|ykfxkh `bv`elx `bxn xlk f{ttkbx `ku no xlk mkfl-

    gb`vmv enktb`be ytnj`oktgx`nb no dnbk"

    Mkxlnhv

    Fkjj f{jx{tk

    Fkjjv uktk mg`bxg`bkh `b Kgejkv m`b`mgj kvvkbx`gj

    mkh`{m ,[MT 79?-97) nt m`b`m{m kvvkbx gj mkh`{m

    gjylg ,FLN) v{yyjkmkbxkh u`xl 79+ ,.) okxgj dn`bk

    vkt{m yj{v ;9 {b xv.mj ykb`f`jj`b* gbh ;9 je.mj vxtkyxn-

    mpf`b ,V`emg)" Xlk fkjjv uktk vkkhkh `b 6;-mm h`vlkv

    gx 79*999 fkjj.fm4 `b xlk vgmk mkh`{m nt xlk vgmk

    mkh`{m u xl xkvx ht{ev" K-8967 h`lphtnfljnt`hk ugv

    y{tflgvkh otnm Xnft`v Fnnavnb @bf"* XKG-Fj ugv otnm

    V`emg gbh `nbnmpf`b otnm Gjk|`v D`nflkm`fgjv" @o bnx

    nxlktu`vk vxgxkh mkh`g ,u xl nt u`xln{x ht{ev) ugv tk-

    yjgfkh kktp 48 l" Goxkt h`ekvx nb u xl xtpyv`b fkjjv

    uktk tkv{vykbhkh `b MKM gbh xlkb uktk fn{bxkh {v`beg dt`elx j`bk fn{bx`be flgmdkt" Ont kjkfxtnylpv`njnep*

    fkjjv uktk vkkhkh nbxn ynjp-J-jpv`bk-xtkgxkh ejgvv fn-

    ktvj`yv gx g hkbv`xp no 79*999 fkjjv.fm4"

    Kjkfxtnylpv`njnep

    Hgxg uktk tkfnthkh u`xl gb G|nygxfl 499D ,G|nb) g YF

    ,Hkjj) gbh Fjgmyk| vnoxugtk ,G|nb)* jxktkh gx

    of = 7 aLs gbh vgmyjkh gx 4"; aLs" Gdn{x ;79 MU

    ygxfl y`ykxxkv uktk y{jjkh {v`be g Ojgm`be-Dtnub y{jjkt

    ,V{xxkt* FG)" Dgxl vnj{x`nb ugv ,`b mM) 6 AFj* 789

    BgFj* 79 Lkykv ,ghc{vxkh xn yL 5"? u xl BgNL)* 4";

    FgFj4* gbh 7"9 MeFj4" Y`ykxxk vnj{x`nb ugv ,`b mM) 789

    AFj* 79 Lkykv ,ghc{vxkh xn yL 5"6 u xl ANL)* 7"9

    MeFj4* 7"9 FgFj4* gbh 77 KEXG ,ghc{vxkh xn yL 5";

    u`xl ANL)" Ulnjk-fkjj f{ttkbxv uktk knakh dp njxgek c{myv no gt`gdjk gmyj`x{hk gbh h{tgx`nb ,gv vykf`kh `b

    xlk xk|x) otnm g lnjh`be ynxkbx gj no

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    D`nflkm`vxtp

    [MT 79?-97 gbh FLN fkjjv uktk ugvlkh u xl 79 mj

    `fk-fnjh YDV gbh jpvkh u`xl r4 mj `fk-fnjh T@YG d{ookt

    ,;9 mM Xt`v yL 5"8* 7;9 mM BgFj* 7 mM KHXG* 7+

    @EKYGJ FG-?69* 9";+ ,u.) hkn|pflnjgxk* 9"7+ ,u.)

    VHV* otkvljp ghhkh 79 mM `nhngfkxgm`hk* ylnvylgxgvk

    gbh ytnxkgvk `bl`d xntv ont 69 m`b gx 8F" Fkjj jpvgxkvuktk fkbxt`o{ekh ont ?9 m`b gx 8F gbh xlk v{yktbgxgbx

    ugv `bf{dgxkh `b VHV vgmyjk d{ookt gx r090;F ont

    7; m`b* djnxxkh gbh vxg`bkh u`xl tgdd`x ynjpfjnbgj gbx -

    LKTE gbx`dnhp ,V`emg) h j{xkh ,73;99) ont 7"; l"

    Mkmdtgbkv uktk fgtko{jjp ugvlkh gbh vxg bkh u xl

    vkfnbhgtp gbx`dnh`kv ont Ukvxktb `v{gj sgx`nb"

    TX-YFT

    mTBG ugv k|xtgfxkh otnm [MT 79?-97 fkjjv {v`be

    Xt` tkgekbx ,V`emg) onjjnukh dp TX-YFT gv hkvft`dkhytk`n{vjp Q6;]" Xlk YFT ytnh{fx ugv gmyj`kh {v`be

    yt`mktv ,;-FEXFXXFGFGFFEXGFXFEEF-6 gbh ;-

    FFGEGEFFGGGEGXEGEFGEE-6 ) fflgba`be g vxtkxfl

    no 4?7 dy dkxukkb xlk vkfnbh gbh on{txl xtgbvmkmdtgbk

    hnmg`bv no tgx KTE" Xlk YFT ytnh{fx ugv fjnbkh `b xlk

    XNYN kfxnt ,@b`xtnekb) gbh fnbtmkh dp g{xnmgxkh

    HBG vkw{kbf`be"

    Hkxktm`bgx`nb no fgjf`{m gbh ytnxk`b fnbxkbx

    [MT 79?-97 fkjjv uktk yjgxkh nb ?9 mm x`vv{k f{jx{tkyjgxkv gx g hkbv`xp no

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    m`hyn`bx ont njxgek gfx`gx`nb gbh g vjnyk ogfxnt* _7.4 =

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    fnbxt`d{x`nb no @XKG xn xlk ytnj oktgx`nb no xlk fkjjv"

    O`e{tk 8D vlnuv xlgx ytnetkvv`k `bftkgvk no xlk fnb-

    fkbxtgx`nb no XKG `b xlk mkh`g ytnyntx`nbgjjp `myg`tkh

    xlk ytnj`oktgx`nb no xlk fkjjv" @b fnbxtgvx bk xlkt 49 jM

    K-8967 bnt 7 mM XKG lgh gbp kookfx nb xlk ytnj`oktg-

    x`nb no xlk FLN fkjjv ,hgxg bnx vlnub)" Nxlkt dtngh-

    vykfxt{m A! flgbbkj djnfaktv v{fl gv 8-gm`bnypt`h`bk

    ,8-GY) gjvn `myg`tkh xlk ytnj`oktgx nb no [MT 79?-97

    fkjjv ,O`e" 8F)" Lnukkt 8-GY `bl`d`xkh xlk ytnj`oktgx`nb

    no FLN fkjjv `bh`fgx`be xlgx `xv kookfxv fn{jh bnx dk gv-

    ft`dkh xn vykf`f `bl`d`x`nb no A! flgbbkjv gv `b xlk fgvk

    no K-8967 gbh XKG" Xlk kookfxv no XKG gbh K-8967 uktk

    ghh`x`k ,O`e" 8H)" Xl{v* xlk hkftkgvk `b ytnj oktgx nb

    fg{vkh dp 9"6 mM XKG fn{jh dk tkvf{kh dp 49 jM

    K-8967 gbh fkjjv ytnj`oktgxkh vj`elxjp dkxxkt xlgb {bxtkgxkh

    fkjjv1 o{txlkt `bftkgvk `b xlk XKG fnbfkbxtgx`nb `bl`d`xkh

    ytnj oktgx`nb kkb `b xlk ytkvkbfk no K-8967" Xlkvk

    ndvktgx`nbv v{eekvx tvx* xlgx g XKG-vkbv`x k gbh g

    K-8967-vkbv`x k flgbbkj ytkvkbx `b [MT 79?-97 fkjjv

    fgb gookfx ytnj`oktgx`nb `b nyynv`xk ugpv gbh vkfnbh*

    xlgx xlk mkflgb`vmv {bhktjp be xlk`t m xnekb`f gbh

    gbx`m`xnekb`f gfx`nb gtk h`vx`bfx"

    @bl`d`x`nb no @K-8967 `v gvvnf`gxkh u`xl fkjj

    hkynjgt`sgx`nb gbh gjxktkh fgjf`{m lnmknvxgv`v

    @b mgbp fkjj xpykv* A! flgbbkjv ytnmnxk ytnj`oktgx`nb dp

    tke{jgx`be fgjf`{m `bffl{|kv xltn{el xlk fnbxtnj no xlk

    mkmdtgbk ynxkbx`gj* xlktkontk uk `bkvx`egxkh ulkxlkt xl`v

    ekbktgj mkflgb`vm ugv tkvynbv`djk ont xlk @K-8967-mkh`gxkh

    O`e" 4 D`nylpv fgj flgtgfxkt vx`fv no @K-8967 f{ttkbxv" ,G) [MT

    79?-97 ulnjk-fkjj f{ttkbxv `b xlk gdvkbfk gbh `b xlk ytkvkbfk no

    49 jM K-8967 `b xlk dgxl vnj{x`nb" Xlk K8967-vkbv`x`k fnmynbkbx`v ndxg`bkh dp v{dxtgfx`be xlk xnxgj f{ttkbx otnm xlk {bdjnfakh f{ttkbx

    ,t`elx)" ,D) Tkytkvkbxgx`k ulnjk-[MT 79?-97 fkjj f{ttkbx knakh dp

    tkykx`x`k njxgek c{myv otnm

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    kookfxv nb xlk ytnj`oktgx nb no [MT 79?-97 fkjjv" Xlk

    nykb`be no A! flgbbkjv ytnh{fkv g f{ttkbx xlgx mnkv xlk

    mkmdtgbk ynxkbx gj xnugth xlk kw{`j`dt`{m ynxkbx gjno ynxgvv`{m gffnth`be xn Kw" 6" @o K-8967 `bl`d`x @A* xlk

    fnbh{fxgbfk ont ynxgvv`{m* EA* flgbekv gffnth`be xn3

    EA EAmg|

    7 ht{e=A bL;

    ulktk EAmg| `v g fnbvxgbx gbh A gbh bL lgk xlk {v{gj

    mkgb`bev" Xlk mkmdtgbk ynxkbx gj* _m* flgbekv dp H_3

    H_ @A

    Em

    EA

    EA E_A _m ?

    ulktk xlk mkmdtgbk fnbh{fxgbfk Em = EA ! E `v

    k|ytkvvkh gv xlk v{m noEAgbh no gjj nxlkt `nbv* E* gbh _A`v xlk kw{`j`dt`{m ynxkbx`gj ont ynxgvv`{m" Xn `bkvx`egxk

    ulkxlkt xlk ytkvkbfk no K-8967 `b xlk dgxl vnj{x`nb gjxktkh

    xlk mkmdtgbk tkvx`be ynxkbx`gj ,MTY) gbh.nt xlk fnbfkb-

    xtgx nb no fpxnvnj`f fgjf`{m* uk kmyjnpkh xlk ygxfl-

    fjgmy xkflb`w{k `b xlk f{ttkbx fjgmy fnbe{tgx`nb gbh

    o{tg-4 m`ftnffl{nt`mkxtp" O`e{tk ;G vlnuv xlgx gyyj`fgx`nb

    no 49 jM K-8967 ,g jkkj v{of`kbx xn `bl`d x xlk

    fnttkvynbh`be vkbv`x`k fnbh{fxgbfk) h`h bnx hkynjgt`sk

    xlk fkjjv ulkb xlk k|xktbgj fnbfkbxtgx`nb no A! ugv

    ylpv`njne`fgj ,6 mM) gbh xlk fnmyn{bh gjvn og jkh xn

    o{txlkt hkynjgt`sk xlk mkmdtgbk `b vpmmkxt`fgj vnj{x`nbv

    ,789 mM* hgxg bnx vlnub)" @b fnbxtgvx* gyyj`fgx`nb no

    ; mM XKG fg{vkh v`eb`fgbx hkynjgt`sgx`nb ,r79 m_*

    hgxg bnx vlnub)" Flgbe`be xlk fnbfkbxtgx`nb no A! otnm

    jnu ,6 mM) xn l`el ,789 mM) gbh `fk ktvg h`h bnx

    knak fgjf`{m-mkh`gxkh ffl{ntkvfkbfk k`xlkt `b xlk gdvkbfk

    O`e" 8 Kookfxv no 8-GY* XKG gbh K-8967 nb xlk ytnj oktgx`nb no

    [MT 79?-97 fkjjv" [MT 79?-97 gbh FLN fkjjv uktk yjgxkh gx

    79*999 fkjjv.fm4 hkbv xp gx hgp 9 gbh uktk fn{bxkh gx 48-l

    `bxktgjv" Hgxg gtk bntmgj`skh xn xlk mg| m{m gj{k `b fnbxtnj

    ,bntmgj skh ytnj`oktgx`nb)" ,G) Ytnj`oktgx`nb no [MT 79?-97 `b

    fnbxtnj fnbh`x`nbv ,f`tfjkv) nt u`xl xlk ghh x`nb no xlk onjjnu`befnbfkbxtgx`nbv no K-8967 `b xlk mkh`g ,`b jM)3 79 ,xt`gbejkv)* 49

    ,vw{gtkv)" @bvkx3 mg|`m{m ytnj oktgx`nb ktv{v K-8967 fnbfkbxtg-

    x`nb" Hgxg gtk otnm < k|ykt`mkbxv" ,D) [MT 79?-97 fkjjv `b xlk

    gdvkbfk.ytkvkbfk no xlk onjjnu`be fnbfkbxtgx`nbv no XKG `b xlk

    mkh g ,`b mM)3 9 ,f tfjkv)* 9"7 ,vw{gtkv)* 9"6 ,xt gbejkv)* 7"9

    ,h`gmnbhv)" Hgxg gtk otnm 8 k|ykt`mkbxv" ,F) Ytnj`oktgx`nb no [MT

    79?-97 ,f`tfjkv) gbh FLN fkjjv ,xt`gbejkv) `b fnbxtnj fnbh x`nbv nt

    u`xl xlk ghh`x`nb no 79 mM 8-GY ,lnjjnu vpmdnjv) `b xlk f{jx{tk

    mkh`g" Hgxg gtk otnm 8 k|ykt`mkbxv" ,H) Ytnj`oktgx`nb no [MT 79?-

    97 fkjjv gx hgp 5 `b xlk gdvkbfk ,h`gmnbhv) nt ytkvkbfk ,vw{gtkv) no

    49 jM K-8967 gbh no xlk `bh fgxkh XKG fnbfkbxtgx`nbv" Hgxg gtk

    otnm 8 k|ykt`mkbxv

    O`e" 6 KTE `v hkxkfxkh `b [MT 79?-97 fkjjv" ,G) Ukvxktb djnx

    `v{gj`sgx`nb u`xl gbx`-LKTE gbx`dnh`kv no FLN fkjjv ,jgbk 7) gbh

    [MT 79?-97 fkjjv ,jgbk 4) jpvgxkv" Xlk gbx dnh`kv hkxkfxkh g

    r749 aHg dgbh ul`fl fnttkvynbhv xn xlk mnjkf{jgt uk`elx no KTE

    nbjp `b [MT 79?-97 jpvgxkv" Xlk mgtakt ugv DkbflMgta ,@b`xtn-

    ekb)" ,D) Gv `b ,G) ont FLN fkjjv ,jgbk 7) nt [MT79?-97 fkjjv`bf{dgxkh ; hgpv u`xl ,jgbk 4) nt u`xln{x ,jgbk 6) 79 jM K-8967" Xn

    gffn{bx ont xlk K-8967-hkykbhkbx ytnj`oktgx`nb xlk fkjjv uktk fn{bxkh

    gbh gb gyytn|`mgxkjp kw{gj b{mdkt no fkjjv ugv {vkh" , F) TX-YFT

    tkkgjv xlk ytkvkbfk no KTE `b [MT 79?-97 fkjjv" mTBG ugv

    k|xtgfxkh otnm [MT 79?-97 fkjjv {v`be Xt` tkgekbx ,V`emg) onjjnukh

    dp TX-YFT" Xlk YFT ytnh{fx vlnub `b jgbk 7 ,r4

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    nt `b xlk ytkvkbfk no K-8967 ,O`e" ;D* b = 8 k|ykt`mkbxv)"

    Xlk og`j{tk no K-8967 xn kj f`x flgbekv `b xlk MTY nt

    fgjf`{m `bxgak ugv ytndgdjp g fnbvkw{kbfk no xlk ogfx xlgx

    K-8967 djnfa`be `v vxgxk-hkykbhkbx" Nb xlk nxlkt lgbh fkjjv

    gtk k|ykfxkh xn k|l`d`x nvf`jjgx`nbv `b xlk mgeb`x{hk no xlk

    MTY h{t`be ygtx`f{jgt ylgvkv no xlk`t fpfjk" Ont `bvxgbfk*

    `x `v xln{elx xlgx mkmdtgbk lpyktynjgt`sgx`nb `bh{fkh dp

    xlk nykb`be no A! flgbbkjv lkjyv xlk xtgbv`x`nb xnugth xlkE7 ylgvk `b vkktgj fkjj xpykv Q;4]" @x `v ynvv`djk xlgx xlk

    `bl`d`xntp gfx`nb no K-8967 xgakv yjgfk h{t`be nbk no xlkvk

    ylgvkv gbh v`bfk djnfa`be `v `ttkktv`djk* xl`v vln{jh tkv{jx

    `b yktmgbkbx hkynjgt sgx`nb" Xn ghhtkvv xl v yn`bx uk

    mkgv{tkh xlk tkvx`be ynxkbx gj `b fkjjv `bf{dgxkh u`xl

    K-8967 nkt ? hgpv" Fkjjv xtkgxkh u`xl K-8967 uktk mntk

    hkynjgt`skh xlgx {bxtkgxkh fkjjv ,O`e" ?G* K-8967-G)"

    Fnbv`vxkbx u`xl xlk bnx`nb xlgx ytnjnbekh njxgek vx`m{-

    jgx`nb `b xlk ytkvkbfk no K-8967 `bh{fk fkjj hkynjgt`sgx`nb*

    xlk MTY ugv mkgv{tkh dkontk gbh goxkt kna`be KTE

    f{ttkbxv dp g xtg`b no 69 hkynjgt`s`be vxkyv xn !?9 m_" Gv

    k|ykfxkh* xlk MTY ugv r74+ mntk ynv`x`k ,b = ;) goxktnjxgek-vx`m{jgx`nb ,O`e" ?G* K-8967-@)" Xn kgj{gxk

    xlk fnbfkbxtgx`nb no fgjf`{m `b fnbxtnj fkjjv nt `b fkjjv

    `bf{dgxkh u`xl K-8967 ont v`| fnbvkf{x`k hgpv uk {vkh g

    a`x xlgx kmyjnpv g m`| no fgjf`{m-vkbv`x`k hpkv ,W{gbx`-

    FltnmXM* D`ngvvgp Vpvxkmv* Lgpugth* FG)" Oj{ntkvfkbfk

    mkgv{tkmkbxv uktk bntmgj`skh ont xlk ytnxk`b fnbxkbx no

    xlk xnxgj jpvgxkv* ul`fl uk gvv{mkh xn dk ytnyntx`nbgj xn

    xlk b{mdkt no fkjjv" Fnbv`vxkbx u`xl n{t ytk`n{v tkv{jxv*

    xlk fgjf`{m fnbxkbx `b fkjjv `bf{dgxkh u`xl K-8967 ugv

    v`eb`fgbxjp `bftkgvkh ,O`e" ?D)" @o KTE flgbbkjv tke{jgxkfgjf`{m `bffl{|* xlk ytkvkbfk no g fgjf`{m `nbnylntk* ul`fl

    mgakv fgjf`{m-vkjkfx`k yntkv `b xlk yjgvmg mkmdtgbk*

    vln{jh `bxktoktk u`xl xlk ytnj`oktgx`k kookfx no K-8967" Gv

    k|ykfxkh* 799 be.mj `nbnmpf`b* g hnvk xlgx fn{jh dk

    xnjktgxkh* `bxktoktkh u`xl xlk ytnj`oktgx`k gfx`nb no K-89673

    fkjjv fn- bf{dgxkh u`xl `nbnmpf`b gbh 49 jM K-8967

    ytnj oktgxkh jkvv xlgb fnbxtnj fkjjv ,O`e" ?F)" Xgakb

    xnekxlkt xlkvk hgxg v{eekvx xlgx fgjf`{m-hkykbhkbx

    ygxlugpv kblgbfk xlk ytnj`oktgx nb no xlk [MT 79?-97

    fkjjv gbh kbhnekbn{v KTE flgbbkjv `bl`d x xlkvk

    ytnfkvvkv"

    H`vf{vv`nb

    Kjkfxtnylpv`njne`fgj* mnjkf{jgt gbh d`nflkm`fgj k`hkbfk

    v{yyntx xlk bnx`nb xlgx kge-tkjgxkh A! flgbbkjv* gtk

    k|ytkvvkh `b gbh k|ktx gb gbx`ytnj`oktgx`k kookfx nb [MT

    79?-97 fkjjv" Xlkvk fkjjv ytnh{fk tnd{vx njxgek-hkykbhkbx

    A! f{ttkbxv xlgx fgb dk ylgtmgfnjne`fgjjp vkygtgxkh `bxn

    xun mgcnt fnmynbkbxv3 g K-8967-v{vfkyx`djk f{ttkbx ul`fl

    `v ytnh{fkh dp KTE gbh ul`fl fnbxt`d{xkv xn tn{eljp 4;+

    xn @A* gbh g XKG-v{vfkyx djk fnmynbkbx gbh ulnvk

    mnjkf{jgt `hkbx xp `v gx ytkvkbx {babnub" Ul jk @XKG `v

    ytnj`oktgx`k* fnbv vxkbx u`xl xlk ukjj-kvxgdj vlkh tnjk no

    A! flgbbkjv `b vx`m{jgx`be m`xnv`v Q4* 40* 64* 6

  • 8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199

    8/10

    xlk ytnj`oktgx`nb no [MT 79?-97 fkjjv d{x u`xl nbk mgcnt

    h`ooktkbfk3 xlgx xlk hkynjgt`sgx`nb-mkh`gxkh `bftkgvk `b

    ytnj`oktgx`nb `v gfl`kkh gx xlk k|ykbvkv no g h`m`b`vlkh

    KTE gfx``xp" G vkfnbh mgcnt h`ooktkbfk tkjgxkv xn xlkmkflgb`vmv tke{jgx`be fgjf`{m `bffl{| ul`fl `v akp xn fkjj

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    mkmdtgbk f{ttkbxv Q66* 8 @b ul`fl ylgvkv no xlk fkjj

    fpfjk `v xlk gfx``xp no A! flgbbkjv ft{f`gj ont ytnj`okt-

    gx`nb> Xlkvk jgp glkgh gbh u`jj dk xlk mgxxkt no o{x{tk

    `bkvx`egx`nbv"

    Gfabnujkhekmkbxv Uk xlgba Htv" S{` Ygb* P{xgag L{tgxg gbh

    C`gbc`k Mg ont lkjy u`xl m`ftnffl{nt`mkxtp* Ht" Cnlb Jkbgth ont ft`x`fgj

    O`e" ? @bl`d`x`nb no @K-8967 gjxktv fgjf`{m lnmknvxgv`v" ,G)

    Mkmdtgbk tkvx`be ynxkbx`gj no fnbxtnj fkjjv nt no fkjjv `bf{dgxkh ont

    ? hgpv u`xl 49 jM K-8967 ,K-8967-G) nt `b xlk ytkvkbfk no xlk vgmkfnbfkbxtgx`nb no K-8967 dkontk gbh goxkt njxgek-vx`m{jgx`nb dp g

    xtg`b no 69 fnbvkf{x`k njxgek c{myv xn !?9 m_ ,otnm gb lnjh`be

    njxgek no

  • 8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199

    9/10

    tkgh`be no xlk mgb{vft`yx gbh F`bs`g Vkvx` ont lkjy u`xl xlk etgyl`fv"

    Xl`v unta ugv v{yyntxkh dp gb B@L Etgbx T97EM? Fgbfkt Tkvkgtfl* ;

  • 8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199

    10/10

    65" Vflj flxkt* J" F"* Yglgy`jj* Y" G"* / Vfl{mgflkt* Y" G" ,7006)"

    Tkf`ytnfgj tke{jgx`nb no A! flgbbkjv dp Fg4! `b `bxgfx l{mgb X

    jpmylnfpxkv" Tkfkyxntv Flgbbkjv* 7,6)* 49747;"

    6